S YS T E M AT I C R E V I E W

Neurophysiology of human touch and eye gaze in

therapeutic relationships and healing: a scoping review
Fiona Kerr 1,3,4,5  Rick Wiechula 1,2  Rebecca Feo 1,2  Tim Schultz 1,2  Alison Kitson 1,2
1
Adelaide Nursing School, University of Adelaide, Adelaide, Australia, 2Centre for Evidence-based Practice South Australia: a Joanna Briggs Institute
Centre of Excellence, 3Faculty of the Professions, University of Adelaide, Adelaide, Australia, 4The NeuroTech Institute Pty. Ltd., Adelaide, Australia,
and 5South Australian Health and Medical Research Institute, Adelaide, Australia

ABSTRACT

Objective: The primary objective of this scoping review was to examine and map the range of neurophysiological impacts
of human touch and eye gaze, and consider their potential relevance to the therapeutic relationship and to healing.
Introduction: Clinicians, and many patients and their relatives, have no doubt as to the efficacy of a positive therapeutic
relationship; however, much evidence is based on self-reporting by the patient or observation by the researcher. There has
been little formal exploration into what is happening in the body to elicit efficacious reactions in patients. There is, however,
a growing body of work on the neurophysiological impact of human interaction. Physical touch and face-to-face
interaction are two central elements of this interaction that produce neurophysiological effects on the body.
Inclusion criteria: This scoping review considered studies that included cognitively intact human subjects in any
setting. This review investigated the neurophysiology of human interaction including touch and eye gaze. It
considered studies that have examined, in a variety of settings, the neurophysiological impacts of touch and eye
gaze. Quantitative studies were included as the aim was to examine objective measures of neurophysiological
changes as a result of human touch and gaze.
Methods: An extensive search of multiple databases was undertaken to identify published research in the English
language with no date restriction. Data extraction was undertaken using an extraction tool developed specifically for
the scoping review objectives.
Results: The results of the review are presented in narrative form supported by tables and concept maps. Sixty-four
studies were included and the majority were related to touch with various types of massage predominating. Only
seven studies investigated gaze with three of these utilizing both touch and gaze. Interventions were delivered by a
variety of providers including nurses, significant others and masseuses. The main neurophysiological measures were
cortisol, oxytocin and noradrenaline.
Conclusions: The aim of this review was to map the neurophysiological impact of human touch and gaze. Although
our interest was in studies that might have implications for the therapeutic relationship, we accepted studies that
explored phenomena outside of the context of a nurse-patient relationship. This allowed exploration of the
boundary of what might be relevant in any therapeutic relationship. Indeed, only a small number of studies included
in the review involved clinicians (all nurses) and patients. There was sufficient consistency in trends evident across
many studies in regard to the beneficial impact of touch and eye gaze to warrant further investigation in the clinical
setting. There is a balance between tightly controlled studies conducted in an artificial (laboratory) setting and/or
using artificial stimuli and those of a more pragmatic nature that are contextually closer to the reality of providing
nursing care. The latter should be encouraged.
Keywords Gaze; healing; neurophysiological; therapeutic relationship; touch
JBI Database System Rev Implement Rep 2019; 17(2):209–247.

Correspondence: Fiona Kerr, [email protected]

Conflict of interest: Author RW is an associate editor of the JBI Database of Systematic Reviews and Implementation Reports.
This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0
(CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way
or used commercially without permission from the journal.
DOI: 10.11124/JBISRIR-2017-003549

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SYSTEMATIC REVIEW F. Kerr et al.

Introduction There are also studies and literature reviews on

he purpose of the review was to examine the the role of trust in health professional (particularly
T connection between two distinct research fields.
The first field is aligned to the social sciences and
nurse)-patient relationships22,23 and the impact of
increasing technological interaction on this thera-
examines the importance of human interaction and peutic relationship.24,25 These studies demonstrate
positive therapeutic relationships for healing and the the increased capacity for hope displayed by the
delivery of fundamental care.1 The second research patient when there is a high trust relationship and
field is aligned to the natural sciences, and inves- personal interaction between the patient and nurse/
tigates the neurophysiological impact of touch and medical practitioner.26,27 The observed interactions
eye gaze during human interaction. Although arising and interconnections that are considered to be rele-
from different research domains, both bodies of vant for improving the healing capacity of patients in
work are strongly connected, with touch and gaze these circumstances include the display of genuine
being key elements of human interaction that have empathy, compassion, direct eye contact and physi-
the potential to influence therapeutic relationships, cal touch.
healing and patients’ experiences of fundamental Whilst clinicians, and many patients and relatives,
care delivery. The connection of these bodies of are in no doubt as to the efficacy of a positive
work is further emphasized by the shared variables therapeutic relationship, much evidence is based
of trust and positivity as relevant mediators of the on self-reporting by the patient or observation by
impact of human interaction. the researcher.23,24 There is, however, a growing
Fundamental care refers to the essential elements body of work on the neurophysiological impact of
of care that every patient requires regardless of their human interaction. Physical touch and face-to-face
clinical condition or the setting in which they are interaction, entailing eye gaze and retinal eye lock,
receiving care. These elements of care can be physical are two types of contact that produce neurophysio-
(e.g. nutrition, hydration, elimination and hygiene), logical effects on the body.20,28,29
psychosocial (e.g. respect, dignity, privacy and cul- There are a growing number of studies investigat-
tural safety) or relational in nature (e.g. empathy and ing the neurophysiological impact of physical touch.
compassion).1 Given the growing evidence that these Such studies have examined the cortical dynamics of
fundamentals are being poorly executed globally, both discriminative (discrimination of stimuli) and
there is increasing emphasis on how they can best affective (pleasant, gentle stroking) touch,30-34 and
be delivered in clinical practice.2-10 Research is the way in which the brain registers (codes) affective
beginning to acknowledge that a positive, trusting touch.35-38 The neurophysiological response to
nurse-patient relationship is integral to the delivery touch includes the release of specific chemicals
of high-quality, person-centered fundamental and neurotransmitters that lead to neuroendocrine
care.1,11 However, the specific neurophysiological effects; vagal stimulation; reduction of stress,
mechanisms through which this positive relationship pain and depression; and enhancement of immu-
impacts patient care and experiences is largely nity.20,39-42 Affective touch also appears to lessen
unknown and unexplored. allostatic load (i.e. stress) in critically ill patients,20
In addition to work on fundamental care, there is due to the positive effects on pathophysiological
a large body of work on the importance of an processes aggravated by stress, such as immune
empathic, therapeutic relationship for healing, and neuroendocrine derangements and inflamma-
patient health, resilience and hope.12-14 This thera- tion.28,39 There is recent evidence of an interoceptive
peutic relationship might involve multiple ‘‘actors’’, effect of affective touch that aids rehabilitation
given that patients can interact with multiple health through alterations to the insular cortex and limbic
professionals in any healthcare episode. Specific system.43
studies focusing on the therapeutic relationship Affective touch is transmitted primarily through
include studies on connectedness,15 social influences stimulation of the nerve’s unmyelinated C-fibers, the
on healing and stress,16,17 meta-analyses of noncon- impact of which is beneficial to healing.29 Affective
tact healing studies18 and reviews of the effect touch is represented in areas of the brain that are
of interpersonal touch on patients19,20 and specific closely related to the perception of emotion and
cells.21 empathy, and this affective-emotional pathway runs

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in part through the spinomesencephalic tract, engag- of the link between these neurophysiological reac-
ing the amygdala, insula and anterior cingulate cor- tions and a decreased level of morbidity and mortal-
tex.29 Resultant neurophysiological reactions can ity through such changes as an increased capacity for
mediate the perception of touch, and are shown to hope,13,60 the capacity to reframe vulnerability and
be beneficial to the healing process, as well as having deal with trauma,61,62 and neurophysiological reac-
a positive effect on a patient’s capacity for pain tions related to the placebo effect.63
management29,44 and a number of physiological In summary, touch and face-to-face interaction
outcomes, including changes to autonomic innerva- with trusted others have a number of neurophysio-
tion through repetition of affective stimulation.20 logical effects that are relevant to the therapeutic
One of the most powerful human interactions is relationship. These neurophysiological effects are
face-to-face contact involving eye gaze. The interac- impacted by the quality of the relationship shared
tion between trusted individuals creates a neural by the individuals. Trust and empathy, in particular,
duet between brains due to the reciprocal firing of appear to be mediators given they have a profound
the brain’s social networking areas, with a powerful effect on the body’s generation and/or secretion of
effect on the level of trust and empathy as well as a beneficial chemicals, such as serotonin.
positive attitudinal shift.45 Face-to-face contact This review maps the research literature on inter-
involves the activation of mirror and spindle neu- ventions that directly or indirectly replicate aspects of
rons.33,46-48 When interacting with trusted others a a therapeutic relationship using touch and/or eye
number of chemicals are released including oxytocin gaze. This research literature arguably complements
and vasopressin,49,50 both of which help to lower the the existing body of research, indicating that thera-
physiological stress response and aid growth and peutic relationships can have a positive impact on
wound healing.51 Social interaction becomes an patients, particularly in relation to the delivery of
interactive process of positive feedback whereby fundamental care. Research evaluating objective
increased levels of oxytocin in turn encourage even neurophysiological measures might provide further
greater levels of gaze to the eye region of human insight as to why and how this positive impact occurs.
faces.50 This dynamic further increases the level of A search of the Cochrane Library, the JBI Database
trust and empathy between the interacting parties. of Systematic Reviews and Implementation Reports
When there is sufficient trust and positivity, a (JBISRIR) and PubMed revealed a very large number of
positive feedback effect can occur, which stimulates systematic reviews primarily concerned with the effects
the parasympathetic nervous system and releases of massage and other forms of touch. Typically these
immune system chemicals that enable neuroplastic- reviews were condition specific such as the impact on
ity and neurogenesis to occur.52,53 These same chem- lower back pain64 or prevention of pressure ulcers.65
icals are involved in immune system strength and These, and many other systematic reviews, typically
changes to hormonal responses triggered by stress, examined clinical outcomes and not neurophysiologi-
pain signalling and integration. Each of these are cal outcomes. One Cochrane systematic review did
directly related to healing and resilience through consider neurophysiological outcomes but was nar-
such mechanisms as modulating the interplay of rowly focused on massage for mental and physical
lymphocytes that produce antibodies54 and trigger- health in infants under the age of six months.66 One
ing hormone and neuropeptide changes that mediate scoping review was identified that mapped massage
emotions.13,55 studies that measured neurophysiological impacts, but
Eye gaze and retinal eye lock between an anxious only in relation to blood pressure.67
person and a trusted ‘‘other’’ has a direct effect on The objectives, inclusion criteria and methods of
the synchronization of the right brain hemi- analysis for this review were specified in advance and
spheres56,57 and the quietening of the sympathetic documented in a protocol.68
nervous system and amygdala,58 increasing the abil-
ity to deal with trauma. Thus, it enables the caregiver Review question/objective
or trusted ‘‘other’’ to ‘‘soothe’’.49,58 This ‘‘eye con- The specific review question for this review was:
tact effect’’ modulates activity in structures in the what are the neurophysiological impacts of human
social brain network,59 aiding communicative inten- touch and eye gaze that have the potential to influ-
tion and affective arousal. There is growing evidence ence healing and the therapeutic relationships?

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SYSTEMATIC REVIEW F. Kerr et al.

The objective of this scoping review was to exam- neurophysiological impacts of touch and eye gaze,
ine and map the range of neurophysiological impacts and which have potential links to the therapeutic
of human touch and eye gaze, and explore possible relationship. Clinical settings included acute care,
links to and implications for the therapeutic rela- long-term care and community care, including
tionship and healing. Touch and gaze are two central the home.
components of human interaction. Understanding
the neurophysiological impact of touch and gaze Types of studies
might provide insights in to how these components This scoping review considered both experimental
of interaction can be used to enhance relationships in and quasi-experimental study designs including:
a therapeutic context. Our intention was not to only randomized controlled trials, non-randomized con-
include studies that overtly stated a link between trolled trials, before and after studies and inter-
touch or gaze and the impact on the therapeutic rupted time-series studies. In addition, analytical
relationship and healing. This would have been too observational studies including but not limited to
restrictive. Our objective was to look broadly at prospective and retrospective cohort studies and
studies that measured the neurophysiological impact case-control studies were considered for inclusion.
of touch and gaze and consider: the contexts in Only quantitative studies were included as the
which these occurred; who received the touch or aim was to examine objective measures of neuro-
gaze and who provided it; what were the variants of physiological changes as a result of human touch
touch and gaze; and what was being measured. In and gaze.
keeping with the purpose of a scoping review, this
information allowed us to explore and map this
emerging research field. Methods
This scoping review adopted the methodology for
Inclusion criteria Joanna Briggs Institute (JBI) scoping reviews as
Participants described in the JBI Reviewers’ Manual.69,70
This scoping review considered studies that included
cognitively intact human subjects of any age. Search strategy
Patients who were heavily sedated or unconscious A three-step search strategy was utilized for this
were excluded. review. An initial limited search of Scopus, PubMed
and CINAHL was undertaken, followed by an anal-
Concept ysis of the text words contained in the title and
This scoping review investigated a number of areas abstract, and of the index terms used to describe
related to the neurophysiology of human interaction the articles. A second search using all identified
(e.g. touch, eye gaze) and their potential connection keywords and index terms was then undertaken
to building a useful therapeutic relationship. The across all included databases. Thirdly, the reference
concept/s examined included: list of all identified reports and articles were searched
 Neurophysiology of touch for additional studies. Only published studies in
 Neurophysiology of eye gaze English were considered for inclusion in this review.
 Neurophysiological impacts on healing The decision not to search for unpublished papers
 Neurophysiology of care was due to the large amount of results from search-
 Therapeutic relationship. ing the databases of published studies, making addi-
tional imprecise searches in the gray literature
Specifically, we considered who received the impractical. There were no date restrictions.
touch or gaze and who provided it; what the variants The databases searched included: CINAHL,
of touch and gaze were; and what outcomes were PubMed, Cochrane Central Register of Controlled
being measured. Trials (CENTRAL), Scopus, PsycINFO and Web
of Science. Results of all searches are provided in
Context Appendix I.
This scoping review considered studies that exam- Initial keywords used were: gaze, healing, neuro-
ined, in either clinical or laboratory settings, the physiological, therapeutic relationship, touch.

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SYSTEMATIC REVIEW F. Kerr et al.

Study selection (9%),82,91,109,119-121 South Korea96,122-124 and the

All searches were imported into Endnote X8 (Clar- UK (6% each).72,103,107,125 Nearly half of the studies
ivate Analytics, PA, USA) and all title and abstracts were randomized controlled trials,42,73,74,77,78,80,
84-90,95,98,99,101,105-108,112,115,116,120,123,124,126-128
were reviewed by two reviewers independently. Full- and
text of studies were then retrieved and reviewed by there were slightly fewer studies involving patients
two reviewers independently. All discrepancies in (45%)72-75,77-80,82,84-87,89,90,92,95-99,101,103,106-108,110,
113,129
selection were resolved through discussion. as opposed to healthy participants. The largest
group of patients were those with cancer.77-79,
95,101,106,107
Extraction of results Fifty-seven studies (89%) investigated
Data were extracted from papers included in the ‘‘touch’’ as an intervention,42,72-93,95-124,126,127,
130,131
scoping review by two independent reviewers using four (6%) investigated the effect of
the data extraction tool specified in the review ‘‘gaze’’,125,129,132,133 two (3%) investigated ‘‘touch
protocol.68 The data extracted included specific and gaze’’ combined94,128 and one study (2%) investi-
details about the populations, concept, context gated touch and gaze with the addition of vocalization
and study methods of significance to the scoping and facial expression.134 It should be noted, that
review question and specific objectives. Any dis- although our aim was to identify studies that addressed
agreements that arose between the reviewers were the neurophysiological impact of touch and gaze in
resolved through discussion. relation to healing there were no studies identified that
addressed this directly.
Data mapping The detailed characteristics of all included studies
The extracted data are presented in both diagram- are provided in Appendix III.
matic and tabular form as per scoping review guide-
lines, including mind-maps of the various aspects of Review findings
the study and how they interrelate. A narrative Interventions and intervention sub-types
summary accompanies the tabulated and diagram- Figure 2 maps the included studies showing the
matic results. numbers of studies investigating each of the inter-
vention types, and for each of the intervention sub-
Results types. The sub-types were derived iteratively as part
Description of studies of the mapping process.
The initial search of all databases was conducted on For studies of touch, the most prominent sub-type
12–13 November 2015 and updated in February was ‘‘massage’’ (46 studies, 81% of touch stud-
2017. The search strategy was deliberately sensitive ies),42,72-75,77-79,81,82,84-92,95-101,105-110,113,115,116,
and therefore resulted in a large number of studies 118-124,126,127,130,131
followed by ’’skin to skin’’ (also
identified. Database searches identified 18,734 known as ‘‘kangaroo care’’) (5 studies, 9%),76,80,
records. Other sources, primarily reference lists of 93,103,104
‘‘warm affective touch/holding’’ (5 studies,
included studies, provided a further 46 records. After 9%)83,102,111,112,114 and ‘‘Reiki touch’’ (1 study,
removal of duplicates and screening of title and 2%).117
abstracts, 86 studies were retrieved in full text and In the ‘‘skin to skin’’ care studies most involved pre-
22 were then excluded based on inclusion criteria term infants,80,93,103,104 with only one study involv-
(See Appendix II). A total of 64 studies have been ing full-term infants;76 all with the mother providing
included in the review. The PRISMA flowchart in the contact. The studies of ‘‘warm affective touch/
Figure 1 describes the flow of decisions for inclusion holding’’ included mother and infant dyads83,102 or
of studies. couples in a relationship.111,112,114 The ‘‘Reiki touch’’
study involved healthy participants with a trained
Characteristics of included studies Reiki practitioner.117 Characteristics of the massage
Of the 64 studies included in the review (Table 1), studies are provided in more detail later.
most (61%) were set in the clinical environment, For studies of gaze, one intervention sub-type
72-110
with the vast majority of studies conducted in (‘‘direct and averted’’) was represented by two stud-
the US (39%),42,79,80,83-90,93,95,97,98,104,106,108,111-117 ies,129,132 others sub-types (‘‘direct, averted and
Sweden (13%),75,77,78,99,100,102,110,118 Japan closed’’ and ‘‘still face’’)125,133 were investigated in

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SYSTEMATIC REVIEW F. Kerr et al.

Records identified Additional records

Identification

through database identified through

searching other sources
(N=18,734) (N=46)

Records after
duplicates removed
(N=13,258)
Screening

Records screened Records excluded

(N=13,258) (N=13,172)
Eligibility

Full-text articles Articles excluded on

assessed for reading full-text
eligibility (N=22)
(N=86)
Included

Number of articles
included
(N=64)

Figure 1: PRISMA flowchart for the scoping review process71

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Table 1: Overview of included studies

Category Variable n %
Setting Clinical (including acute, long term community and home care) 39 61
Laboratory 25 39
USA 25 39
Sweden 8 13
Japan 6 9
South Korea 4 6
UK 4 6
Israel 3 5
Australia 2 3
Country Finland 2 3
Germany 2 3
Iran 2 3
Brazil 1 2
Canada 1 2
Switzerland 1 2
Taiwan 1 2
Thailand 1 2
Turkey 1 2
Randomized Controlled Trials 31 48
Non-randomized controlled trials 17 27
Study design Pre-test post-test 7 11
Case-Series 7 11
Other 2 3
Population Healthy 35 55
Patients 29 45
Touch 57 89
Intervention Gaze 4 6
Touch and gaze 2 3
Touch, gaze, vocalisation, facial expression 1 2

one study each. One study involved mothers and play’’94 and ‘‘still face and touch’’.128 Both studies
infants.125 The other three studies involved women involved parents and their children. One study focused
and men viewing the gaze of either the researcher,129 or on the combined intervention of ‘‘touch, gaze, vocal-
of live models.132,133 For the two studies of touch and isation and facial expression’’, and examined the inter-
gaze (combined), the intervention sub-types were ‘‘free vention sub-type of ‘‘social interaction’’. This study

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SYSTEMATIC REVIEW F. Kerr et al.

Figure 2: Mapping of intervention types and outcome measures (values correspond to the number of
studies as does the relative size of each component of the figure)

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SYSTEMATIC REVIEW F. Kerr et al.

included a variety of participants including couples and (n ¼ 28);42,73-75,78,79,81,82,84-87,90,91,95,97-99,106,

parents with children.134 108,110,113,116,119,120,124,126,131
back (n ¼ 4);89,
115,118,121
Figure 3 presents a detailed analysis of the key back, neck and head (n ¼ 2);101,105
characteristics of ‘‘massage’’, the most frequently limbs (n ¼ 3);77,92,100 neck and shoulders
measured intervention sub-type. Many studies failed (n ¼ 1);127 scalp (n ¼ 1);123 trunk (n ¼ 1);96
to provide various details of these characteristics; upper body and limbs (n ¼ 3);72,88,109 acupres-
therefore, the totals for some characteristics in sure points (n ¼ 2);122,130 and self-selected
Figure 3 are less than 46. (n ¼ 1).107
Six aspects of massage apparent from the litera- (ii) Type: The style of massage being provided,
ture are presented: ranging from gentle/tactile (n ¼ 9),72,75,
77,78,98,100,109,110
(i) Body area: The different amounts/locations of and Swedish (n ¼ 7),88,90,
101,108,115,118,131
the body being massaged, including: full body to other forms such as anma

Figure 3: Mapping of ‘‘massage’’ intervention study characteristics (values correspond to the number of
studies as does the relative size of each component of the figure)

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SYSTEMATIC REVIEW F. Kerr et al.

(n ¼ 3),82,119,120 shantala,81 Thai126 and Yak- measured in 23% (n ¼ 15) of studies and this was
son.96 Nine studies used multiple types of mostly serum oxytocin.42,75,77,94,102,109,111,112,114-
massage,42,73,74,95,105-107,113,116 and a further 116,118,125,127,134
The next most frequent group of
12 did not specify the type of massage outcome measures were the catecholamines: dopa-
used.79,84-87,89,91,92,121,123,127,130 mine, epinephrine (adrenaline) and norepinephrine
(iii) Relationship to provider (where stated): The (noradrenaline) in 19% (n ¼ 12) of stud-
provider was either a trained masseuse (n ¼ 27) ies.72,79,85,87,89,95,96,98,110,111,113,123 Serotonin was
or researcher/research assistant (n ¼ 1) that measured in only 8% (n ¼ 5) of studies.79,85,87,95,101
had no existing relationship with the recipi- Neural activity including EEG, amygdala response
ent;42,75,78,79,81,86-90,92,95,101,106,108,110,113,115, and N170, a component of event related potential
116,118-120,122-124,126,130,131
a trained clinician (stimulus in response to viewing faces), were mea-
involved in the subject’s care (all nurses: sured in a small number of studies involving
n ¼ 9);72,74,77,96,97,99,100,105,107 or a significant gaze129,132 and massage.88,124,130
other (a person in a relationship with the It should be noted that the inclusion criteria also
receiver) (n ¼ 6).73,84,85,91,109,127 addressed studies in regard to the neurophysiology of
(iv) Duration: The duration of the massage, ranging healing, care and the therapeutic relationship.
from less than 20 minutes (n ¼ 12),81,87, Although many included studies made inferences
88,91,96,98,105,115,121,123,127,130
20–40 minutes about the potential for the various neurophysiologi-
(n ¼ 18)72,77,79,82,85,86,89,90,92,95,99,101,107,109, cal measures and we have explored this potential, no
118,120,124
to greater than 40 minutes studies were identified that directly measured the
(n ¼ 12).42,73-75,78,97,100,108,113,116,126,131 neurophysiological impact on these concepts. This
(v) Frequency: Whether the massage was con- issue is elaborated in the following discussion.
ducted once (n ¼ 14)42,72-74,99,100,107,115,118,
120,122,126,127,130
or multiple times Discussion
(n ¼ 31).75,77-79,81,82,84-92,95-98,101,105,106, As this is a scoping review, the included studies have
108-110,113,116,119,123,124,131
not been subjected to critical appraisal. There is
(vi) Control: If a control group was used, the most therefore no attempt to address the effectiveness
frequently occurring comparator was no mas- of the interventions.
sage (n ¼ 14),72,73,84,91,92,95,97,98,105,109,113, The impetus for this review was the growing body
123,124,131
followed by rest (n ¼ 9)82,99- of work on the neurophysiological impact of touch
101,106,115,118,119,126
and then relaxation and eye gaze during direct human interaction and the
(n ¼ 6).79,85,86,88,90,110 A small number of benefits of a positive, trusting therapeutic relation-
studies used gentle touch (n ¼ 3)42,96,116 and ship as the central element in the delivery of high-
attentive discussion (n ¼ 3).77,78,127 One study quality, person-centered fundamental care.11,135
used video viewing.89 Due to study design, This review, therefore, aimed to identify research
three studies had no comparator.75,81,121 that evaluated neurophysiological measures as a
response to touch and gaze, given they are essential
Outcomes elements of establishing and maintaining therapeutic
Figure 2 also presents the outcomes measured for all relationships. We considered the nature of the inter-
of the included studies. The most common outcome ventions in terms of what intervention was delivered,
measure was cortisol accounting for 83% (n ¼ 53) of who administered the intervention and who
studies. This included salivary cortisol in 48% received it.
(n ¼ 31),42,76-78,80-84,86,88-94,100,104,106,112,113,116,117, Although we identified a large body of research,
119-121,124,126,128
serum cortisol in 28% arguably only a small number of studies measured
(n ¼ 18)42,72-75,80,97,99,101,103,105,107,111,116,122-124, relevant neurophysiological responses and were
131
and urinary cortisol in 17% (n ¼ 11) of stud- contextually specific to what could be described
ies.79,85-87,89,95,96,98,108,110,113 It should be noted as the development and maintenance of a
that in a number of studies, two sources of cortisol clinician-patient relationship. These studies
were sampled. None of the studies with gaze as a involved patients and clinicians (all nurses) in
sole intervention measured cortisol. Oxytocin was the clinical setting.72,74,77,96,97,99,100,105,107 However,

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SYSTEMATIC REVIEW F. Kerr et al.

to restrict the review to these studies alone would have group massaged by a significant other, most often a
prevented exploration of a number of aspects of touch spouse or life partner, and half as many again from a
and gaze. For example, the effect of gaze was not trained clinician. Whilst only four studies reported
addressed in any of the studies involving nurses. clinicians providing touch on more than three occa-
The scoping review methodology allows, even sions,77,96,97,105 the trust engendered by an ongoing
encourages, the exploration of the boundaries of a relationship with a nurse or other type of clinician
concept. We would assert that therapeutic relation- during therapy (either in a hospital or undergoing
ships are not restricted to a nurse and patient. These regular treatment) might offer potential benefits in
relationships can and often do include relatives of regard to the therapeutic relationship and patient
patients, with nurses often including them in thera- recovery/healing.
peutic activities. In the case of infants, this would In the present review, the decision was made to
include encouraging mothers to have skin-to-skin only include studies with ‘‘live’’ gaze, and not the
contact. We established our boundary at the point presentation of photos or videos, due to the body of
where objective measurement of direct human to evidence indicating a difference in the neurophysio-
human touch and gaze occurred. Regarding the types logical reaction to ‘‘live’’ gaze as opposed to gaze
of touch and the inclusion of massage, there is a that is intermediated by technology (i.e. interaction
continuum from light or gentle affective touch to over a screen, images of faces).132,133 As a result,
firm even forceful touch of deep tissue massage. only seven studies addressing gaze (with or without
There is no natural cut-off point within this range. touch) were included.94,125,128,129,132,134 These stud-
We recognize that gentle affective touch would occur ies measured both the effect of direct and averted
when a nurse is giving comfort to a patient. At the gaze. This is relevant for the nurse-patient relation-
other end of the spectrum nurses will touch patients ship as a more intense physiological response from
more firmly when technical care is provided and it is the stimulus of direct gaze might result in a greater
this boundary which we aimed to explore. level of cognitive social network engagement which
The actions of nurses when caring for patients could lead to interpersonal neural synchronization
involve a great deal of touch.136,137 This includes and an increase in empathy.133 It might also result in
touch that would be intended to comfort (gentle an increase in neuro-chemicals that strengthen the
touch) and, as part of an intervention, technical or endocrine system and modulate the stress response.
instrumental touch.138 In considering touch in the However, no studies that involved gaze between a
context of nursing practice, a bed-bound patient patient and nurse were identified in the search.
requiring washing by a nurse might also be provided The majority of included studies measured a
with gentle massage, which would closely approxi- single intervention, either touch or gaze. In the
mate some studies in the current review where a back studies that involved touch, it is reasonable to
massage was the intervention. There were a small assume that those providing touch might be making
number of included studies involving holding; warm, eye contact with the subjects; however, only a small
affective touch; and skin-to-skin contact, and number of studies noted the potential for, or effect
once again these studies would contextually relate of, direct eye gaze as a mediating factor on results.
to the use of touch by nurses to comfort a This appears to be due to the lack of awareness of the
patient.76,80,83,93,102-104,111,112,114 Other aspects potential neurophysiological impact of direct eye
related to touch that were reflected in the studies gaze and therefore, the lack of recognition of its role
included the skill level of the masseur/therapeutic in moderating or mediating outcomes. Only three
provider and the relationship they had to the person studies explicitly involved interventions of both
receiving touch. touch and gaze.94,128,134 Notably one recent study
Trust is considered foundational in any therapeu- included an intervention involving the synchrony
tic relationship.23,135 A trusting relationship is codes of touch, gaze, vocalization and facial expres-
considered to be ‘‘dynamic and ongoing’’,23(p506) sion, and its ‘‘pragmatic’’ design meant it was one of
suggesting that those who form this relationship the few studies to attempt to control for the reality of
are known to each other and have multiple inter- the complexity of human-to-human interaction.134
actions. The majority of studies had massage pro- A number of different population groups received
vided by a trained masseuse, with the next largest interventions. Approximately half of the studies

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SYSTEMATIC REVIEW F. Kerr et al.

involved the intervention being administered to involving firm pressure (such as Swedish massage)
patients with a variety of medical conditions; the was reported to increase cortisol (due to pressure
largest group being people with cancer.77- sensors in the skin); yet, it had other beneficial
79,95,101,106,107
Many studies aimed to use touch to physiological impacts such as stimulation of oxyto-
reduce anxiety and stress, which is common in cin and immune system function. In many of the
patient population groups. A few of the studies studies that had oxytocin as an outcome measure, it
focusing on healthy individuals used a range of was used as an indicator of bonding and/or syn-
mechanisms to induce stress in the subjects before chrony. Though not part of this review’s objectives,
or after the intervention process, which included there was a consistent link reported between raised
touch, gaze and proximity to a trusted or significant oxytocin and an increase in immunological activity,
other.99,114,127 A number of these studies reported and this warrants further research in terms of the
results that can potentially inform how to mediate potentially beneficial outcomes from direct interac-
stress via the therapeutic relationship. tion with the clinician. It also raises the potential of
The environment in which the intervention was using oxytocin as a measure of the development of a
provided was also a consideration in a number of the therapeutic relationship; however, in the studies
studies. Approximately half of the studies were with nurses, only one measured oxytocin levels
undertaken in a non-clinical environment where and the rationale was that it was an anxiolytic.77
conditions could be well-controlled in terms of stim- A small number of studies measured neurological
uli not directly related to the human-to-human inter- changes including amygdala and other neural activ-
action, such as light and noise. Although the studies ity, changes in nervous system activity and vagal
undertaken in a clinical setting might be considered tone, and the presence of various neurochemicals/
more relevant, there was no direct attempt to control transmitters in response to study interventions.128-
130,132,133
for such environmental stimuli. The reported results were consistent with
For the majority of studies (n ¼ 53), the major the body of research work regarding the beneficial
impact marker tested was cortisol,42,72-101,103- neurophysiological effects of direct human interac-
108,110-113,116,117,119-124,126-128,131
with 15 studies tion.30-41
measuring oxytocin.42,75,77,94,102,109,111,112,114-116, Nursing interventions are often complex with
118,125,127,134
Cortisol levels were measured in many confounders. Qualitative research investigat-
serum, saliva and/or urine. In the nine studies that ing touch as part of nurse-patient interaction reports
involved patients with nurses providing (gentle) that gentle touch can result in comfort or distress
touch, cortisol levels were measured as an indicator depending on a range of contextual issues, such as
of stress.72,74,77,96,97,99,100,105,107 In many cases, the the gender of the nurse, the environment in which the
purpose of touch therapy was to reduce stress in touch is administered, and the simple but important
patients, and in some it was to explore beneficial act of explaining what is happening before the touch
neurophysiological effects (including immunologi- is administered.136,138 Looking for objective evi-
cal), particularly when the patient was undergoing dence about the impact of a good therapeutic rela-
treatment. Direct eye gaze was also indicated as a de- tionship is challenging, confounded by the iterative
stressor in the studies that examined at it as an and synergistic neurophysiological nature of direct
intervention.94,125,128,129,132-134 This highlights interaction on both parties.99 The majority of studies
the potential for touch and eye gaze, as part of that we identified aimed to measure the impact of a
the nurse-patient relationship, to positively impact single intervention, most commonly massage, often
patients, as supported by findings showing an inte- ignoring the additional moderation/mediation of
grative role of the oxytocinergic system in support- direct eye gaze. The interventions were rarely within
ing social affiliation, and an associated rise in the context of the nurse-patient relationship.
immune biomarkers.134
Cortisol was shown to be a complex indicator, as Limitations
a number of variables are involved, including rela- One potential limitation of this review is that we
tionship, gender, age, baseline/resting level, type of focused specifically on touch and gaze as central
touch, type of cortisol (salivary, plasma and urinary) elements of human interaction, including as part
and collection method. For example, massage of a therapeutic relationship, in studies that

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SYSTEMATIC REVIEW F. Kerr et al.

quantifiably measured neurophysiological outcomes to the reality of providing nursing care. The latter
of such interaction. Human interaction is much should be encouraged.
more complex than touch and gaze, as shown in
those studies that included related aspects such as Recommendations for research
social synchrony, convergence of biomarkers during Given the growing evidence that fundamental care
bonding and affiliation, and the interplay of such is being poorly executed globally,2-10 there is
things as allostasis and trust. There are also many increasing emphasis on understanding how such
studies that explore the neurophysiological impact care can be delivered effectively and safely and
of other aspects of human interaction, either inclu- on elucidating the positive impact for patients
sive or exclusive of touch and gaze, using qualitative when such care is delivered well. Fundamental care
methodologies. Such studies, when robust, should involves multiple opportunities for touch (as part of
also inform this area of research as the complex routine activities, such as bathing, or intended to
interplay cannot be measured by quantitative mea- comfort) and gaze, and is positively influenced by a
sures alone. trusting nurse-patient relationship. Systematic
Regarding gaze, the decision was made to only reviews of effectiveness could help to elucidate
include ‘‘live’’ faces and this restricted the literature the specific neurophysiological mechanisms though
we accessed. A further limitation is that, due to the which nurses’ routine work and fundamental care
complexity of cultural differences in regard to direct result in positive care experiences for patients and
gaze and touch, this review has not included cultural improved patient healing. These reviews would
difference as a criterion. This was compounded by range from those considering the neurophysiologi-
only including English language studies. Future cal effect of massage as a standalone intervention,
research in this area would be valuable in terms of likely to include a large number of studies, to a
informing nurses and other clinicians on the complex review on the effectiveness of comforting touch by
mediating effects. nurses, likely to include only a small number of
Finally, it should be noted that we did not search studies. There is also potential for reviews in a
for unpublished literature. In preparation for this number of other areas including neural engagement
review we deemed a comprehensive search for and synchronization and immunological change.
unpublished papers impractical. As this is a scoping In regard to primary research, most of the
review without critical appraisal we make no specific included studies were designed to control for a single
judgments of effect which would be an issue in stimulus. Very few studies were conducted in the
relation to publication bias. clinical setting with the multiple stimuli that would
represent the reality and complexity of nurse-patient
Conclusion interaction. However, these studies demonstrated
The aim of this review was to identify studies that the feasibility of this type of pragmatic research.
evaluated two important elements of human inter- Studies in which nurses are the providers of the
action, touch and gaze, and their impact on a range intervention should be undertaken in the clinical
of neurophysiological measures. An important con- area, to further explore the impact of the relationship
sideration was the relevance of the studies in regard between patient and nurse, and it would be relevant
to the nurse-patient relationship, interpreted to further explore such an impact on both parties, as
through the wider lens of the therapeutic relation- informed by studies regarding the reciprocal nature
ship. Although small in number, there were studies of the neurophysiological impacts of direct human
that did involve nurses and patients, but most did not interaction. The study by Ulmer-Yaniv et al.134 pro-
address the complexity of human interaction as vides a methodological example of quantifying mul-
would be seen in the clinical setting. However, there tiple convergent elements and outcomes of human
was sufficient consistency in trends evident across interaction. Other studies have also used video and
many studies regarding the beneficial impact of accompanying software to code interactions
touch and eye gaze to warrant investigation in the between individuals in both the clinical and simu-
clinical setting. There is a balance here between lated environments, also demonstrating feasibility of
studies that are tightly controlled and those of a this approach.139,140 In the early 1990 s, Estabrooks
more pragmatic nature that are contextually closer and Morse used a grounded theory approach to

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SYSTEMATIC REVIEW F. Kerr et al.

Appendix I: Search strategies

All searches conducted in February 2017

Source Query Results

CINAHL (touch or massage or gaze or retinal or eye) AND (oxytocin or 259
vasopressin or cortisol or dopamine or serotonin or amygdala)
Cochrane (touch or massage or gaze or retinal or eye) AND (oxytocin or 634
(CENTRAL) vasopressin or cortisol or dopamine or serotonin or amygdala)
PubMed ((oxytocin[Title/Abstract] OR cortisol[Title/Abstract] OR dopamine[Ti- 3932
tle/Abstract] OR serotonin[Title/Abstract] OR vasopressin[Title/Abstract]
OR amygdala[Title/Abstract])) AND ((touch[Title/Abstract] OR massa-
ge[Title/Abstract] OR gaze[Title/Abstract] OR retinal[Title/Abstract] OR
eye[Title/Abstract])
JBISRIR (touch OR massage OR gaze OR retinal OR eye) AND (oxytocin OR 36
vasopressin OR cortisol OR dopamine OR serotonin OR amygdala)
Web of Science (touch or massage or gaze or retinal or eye) AND (oxytocin or 5276
vasopressin or cortisol or dopamine or serotonin or amygdala)
Scopus (touch or massage or gaze or retinal or eye) AND (oxytocin or 6959
vasopressin or cortisol or dopamine or serotonin or amygdala)
PsycINFO ((touch or massage or gaze or retinal or eye).mp. [mp ¼ title, abstract, 1638
heading word, table of contents, key concepts, original title, tests &
measures]) AND ((oxytocin or cortisol or dopamine or serotonin or
vasopressin or amygdala).mp. [mp ¼ title, abstract, heading word, table
of contents, key concepts, original title, tests & measures])
Note that MeSH (Medical Subject Headings) were not used in any of the searches.

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SYSTEMATIC REVIEW F. Kerr et al.

Appendix II: Excluded studies based on eligibility criteria

Busch M, Visser A, Eybrechts M, van Komen R, Oen I, Olff M, et al. The implementation and evaluation of
therapeutic touch in burn patients: an instructive experience of conducting a scientific study within a non-
academic nursing setting. Patient Educ Couns. 2012;89(3):439–46.
Reason for exclusion: No skin-to-skin contact
Chatel-Goldman J, Congedo M, Jutten C, Schwartz JL. Touch increases autonomic coupling between
romantic partners. Front Behav Neurosci. 2014;8:95.
Reason for exclusion: No reporting of neurophysiological measures
Currin J, Meister EA. A hospital-based intervention using massage to reduce distress among oncology
patients. Cancer Nurs. 2008;31(3):214–21.
Reason for exclusion: No reporting of neurophysiological measures
Gordon I, Voos AC, Bennett RH, Bolling DZ, Pelphrey KA, Kaiser MD. Brain mechanisms for processing
affective touch. Hum Brain Mapp. 2013;34(4):914–22.
Reason for exclusion: No skin-to-skin contact
Groer M, Mozingo J, Droppleman P, Davis M, Jolly ML, Boynton M, et al. Measures of salivary secretory
immunoglobulin A and state anxiety after a nursing back rub. Appl Nurs Res. 1994;7(1):2–6.
Reason for exclusion: No reporting of neurophysiological measures
Helminen TM, Kaasinen SM, Hietanen JK. Eye contact and arousal: the effects of stimulus duration. Biol
Psychol. 2011;88(1):124–30.
Reason for exclusion: Only measured skin conductance response
Henricson M, Berglund AL, Maatta S, Ekman R, Segesten K. The outcome of tactile touch on oxytocin in
intensive care patients: a randomised controlled trial. J Clin Nurs. 2008;17(19):2624–33.
Reason for exclusion: Patients semi-conscious or unconscious
Hodgson NA, Lafferty D. Reflexology versus Swedish Massage to Reduce Physiologic Stress and Pain and
Improve Mood in Nursing Home Residents with Cancer: A Pilot Trial. Evid Based Complement Alternat
Med. 2012;2012:456897.
Reason for exclusion: Some participants not capable of providing consent so surrogate was used
Kanitz JL, Reif M, Rihs C, Krause I, Seifert G. A randomised, controlled, single-blinded study on the impact
of a single rhythmical massage (anthroposophic medicine) on well-being and salivary cortisol in healthy
adults. Complement Ther Med. 2015;23(5):685–92.
Reason for exclusion: No detailed reporting of salivary cortisol
Kujala MV, Carlson S, Hari R. Engagement of amygdala in third-person view of face-to-face interaction.
Hum Brain Mapp. 2012;33(8):1753–62.
Reason for exclusion: Subject not directly involved in interaction but observing others
Lee MS, Rim YH, Kang CW. Effects of external qi-therapy on emotions, electroencephalograms, and plasma
cortisol. Int J Neurosci. 2004;114(11):1493–502.
Reason for exclusion: No skin-to-skin contact
Lee YH, Park BN, Kim SH. The effects of heat and massage application on autonomic nervous system.
Yonsei Med J. 2011;52(6):982–9.

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SYSTEMATIC REVIEW F. Kerr et al.

Reason for exclusion: No skin-to-skin contact

Listing M, Krohn M, Kim I, Reisshauer A, Peters E, Liezmann C, et al. The Influence of Classical Massage
Therapy on Stress Perception, Mood Disturbances, Body Image, Cortisol and Oxytocin Levels 2011. 389- p.
Reason for exclusion: Conference paper unable to access full-text
Okvat HA, Oz MC, Ting W, Namerow PB. Massage therapy for patients undergoing cardiac catheterization.
Altern Ther Health Med. 2002;8(3):68–70, 2, 4–5.
Reason for exclusion: Cortisol only raised in discussion
Peled-Avron L, Wagner S, Perry A, Shamay-Tsoory S. Get in touch: the role of oxytocin in social touch2013.
S90-S p.
Reason for exclusion: Conference paper unable to access full-text
Pierno AC, Becchio C, Turella L, Tubaldi F, Castiello U. Observing social interactions: the effect of gaze. Soc
Neurosci. 2008;3(1):51–9.
Reason for exclusion: Not live faces
Ponkanen LM, Hietanen JK, Peltola MJ, Kauppinen PK, Haapalainen A, Leppanen JM. Facing a real person:
an event-related potential study. Neuroreport. 2008;19(4):497–501.
Reason for exclusion: Unable to access full-text
Rapaport M, L. Hale K, Koury M, Shubov A, J. Bresee C. The role of oxytoncin, vasopressin and cortisol in
the beneficial effects of massage therapy 2008. 1S-S p.
Reason for exclusion: Conference paper unable to access full-text
Sato W, Kochiyama T, Uono S, Toichi M. Neural mechanisms underlying conscious and unconscious
attentional shifts triggered by eye gaze. Neuroimage. 2016;124(Pt A):118–26.
Reason for exclusion: Not live faces
Sato W, Kochiyama T, Uono S, Yoshikawa S. Amygdala integrates emotional expression and gaze direction
in response to dynamic facial expressions. Neuroimage. 2010;50(4):1658–65.
Reason for exclusion: Not live faces
Sato W, Yoshikawa S, Kochiyama T, Matsumura M. The amygdala processes the emotional significance of
facial expressions: an fMRI investigation using the interaction between expression and face direction.
Neuroimage. 2004;22(2):1006–13.
Reason for exclusion: Not live faces
Sauer A, Mothes-Lasch M, Miltner WH, Straube T. Effects of gaze direction, head orientation and valence of
facial expression on amygdala activity. Soc Cogn Affect Neurosci. 2014;9(8):1246–52.
Reason for exclusion: Not live faces

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SYSTEMATIC REVIEW F. Kerr et al.

Appendix III: Characteristics of included studies

Citation Study aims Setting Study Type Population (N ¼ ) Intervention Outcomes Key findings

Acolet et al. To assess the bio- UK, Clinical Non-RCT Stable pre-term Gentle massage of the Cortisol Cortisol concentrations were
(1993)72 chemical and clini- infants (16) trunk and limbs using (plasma) Epi- consistently reduced after
cal response to arachis oil for approxi- nephrine massage. No significant differ-
massage in preterm mately 20 minutes (only Norepinephrine ence detected between the
infants one massage) change in cortisol concentra-
Provider: massage tion in the group receiving
trained clinician (nurse) massage and in the control
Comparator(s) group.
Control (no massage)
Adib-Hajbagh- To evaluate the Iran, Clinical RCT Male patients in 60-min. whole body Cortisol In the group massaged by the
ery, Rajabi- effect of whole body CCU (60) massage. Techniques (plasma) patients’ companions, the
Beheshtabad & massage performed used included static mas- mean of blood cortisol was
Abasi (2013)73 by a patient’s com- sage, superficial stretch- 323.6  162.6 nanomoles,
panion on the level ing technique, stretching which decreased to
of blood cortisol massage, lymph vacuum- 268.4  141.1 after the inter-
among patients ing technique, latitudinal vention (P < 0.102). The mean
admitted in the rubbing technique, and of blood cortisol in the con-
CCU myofacial releasing tech- trol group did not change
nique, accompanied with significantly.
effleurage using almond
oil.
Provider: patient’s com-
panion
Comparator(s)
Control (no massage,
routine care)
Adib-Hajbagh- To compare the Iran, Clinical RCT Male patients in One 60-minute, whole Cortisol In the nurse group, the
ery, Rajabi- effect of massage CCU (90) body massage. The tech- (plasma) median blood cortisol level
Beheshtabad, applied by a nurse niques used were static was decreased after the inter-
Ardjmand specialist and massage, superficial vention (P < 0.007). The
(2015)74 patients’ relatives on stretching technique, median blood cortisol level for
blood cortisol level stretching massage, the patients’ relatives and con-
among patients lymph vacuuming tech- trol group did not change
admitted in CCU nique, latitudinal rub- significantly. There was no
bing technique and significant difference between
myofascial releasing the cortisol level in the three
technique, which were groups either before or after
accompanied with effleu- the intervention.
rage of almond oil.
Provider: massage
trained clinician (nurse)
Comparator(s)
(1) One session of 60-
minute, whole body
massage by patients’
relatives (2) Control (no
massage, routine care)
Andersson, To investigate how Sweden, Clin- Pre-test post- Women with Whole-body massage for Cortisol No statistically significant dif-
Wändell & TM, short term and ical test Type 2 diabetes 60 minutes 1/week for (plasma) Oxy- ferences were found regarding
Törnkvist over time, affects (11) 10 weeks. Tactile mas- tocin (plasma) oxytocin, however, the oxyto-
(2004)75 blood glucose, stress sage (TM): pain-free but cin measurements did show
hormones and well- deliberate, gentle and tendencies to decline over
being in women superficial massage of time, with the lowest value
with type 2 diabetes the skin without manip- measured on occasion 3. The
mellitus ulation of the underlying S-cortisol value on occasion 2
muscles. Odourless vege- showed a statistically signifi-
table oil. Quiet music is cant reduction (p < 0.05).
played during the mas-
sage. Three measurement
times: before massage,
one week after and
twelve weeks after.
Provider: trained mas-
seuse
Bennett et al. To examine the Thailand, RCT Physiotherapy stu- Whole body TTM was Salivary cortisol No evidence to indicate that
(2016)126 acute effects of Lab dents with self- applied to participants in collected single TTM could decrease
TTM on cortisol perceived stress the TTM group for 90 between 10:00 saliva cortisol when compared
level, blood pres- score equal to or minutes. and 12:00 and with rest in the supine posi-
sure, heart rate and greater than 3 on Provider: trained mas- then after the tion.
stress perception in a 5-point scale seuse procedure
academic stress (rated by 1 ¼ not Comparator(s)
stressed at all and Participants were awake
5 ¼ extremely resting in the supine
stressed) (36) position for 90 minutes

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SYSTEMATIC REVIEW F. Kerr et al.

(Continued)
Citation Study aims Setting Study Type Population (N ¼ ) Intervention Outcomes Key findings

Bigelow et al. To investigate the Canada, Non-RCT Mothers and their Mothers in the SSC Cortisol (sali- Mean values for salivary corti-
(2012)76 effect of mother/ Home Visits full-term infants group provided approxi- vary) sol for the one-week visit were
infant SSC on (90) mately 5 hours per day .340 mg/dL (SD ¼ .163) for the
mothers’ postpar- of SSC with their infants SSC group and .278 mg/dL
tum depressive in the infants’ first week (SD ¼ .128) for the control
symptoms during and then more than group. The mean values for
the first 3 postpar- 2 hours per day until the the one-month visit were
tum months and infants were age one .234 mg/dL (SD ¼ .095) for the
their physiological month. Saliva samples SSC group and .244 mg/dL
stress during the were taken from the (SD ¼ .161) for the control
first postpartum mothers when the group. Over their infants’ first
month infants were one week month, mothers in the SSC
and one month. group had a greater reduction
Provider: mothers in their salivary cortisol than
Comparator(s) mothers in the control group.
Control (mothers pro-
vided little or no SSC)
Billhult et al. To examine the Sweden, Clin- RCT Women with Effleurage massage ther- Cortisol (sali- No significant changes
(2008)77 effect of repeated ical breast cancer apy (20 minutes of vary) Oxytocin between groups were detected
effleurage massage undergoing radia- effleurage on ten occa- (plasma) on cortisol and oxytocin con-
treatments com- tion therapy (22) sions), directly after the Lymphocytes centrations.
pared with a visit scheduled radiation. The
control group on patients could choose
circulating lympho- between massage on
cytes, levels of corti- either both feet/lower
sol in saliva and legs or both hands/lower
oxytocin in plasma arms. Cold-pressed vege-
as well as degree table oil was used, and
anxiety, depression the limb was wrapped in
and quality of life, a towel after the mas-
in women with sage.
breast cancer Provider: massage
trained clinician (nurse)
Comparator(s)
The control group was
given the same amount
of attention as the mas-
sage group but did not
receive massage.
Billhult et al. To examine the Sweden, Clin- RCT Women with A single 45 min. full- Cortisol (sali- No significant differences
(2009)78 short-term effects of ical breast cancer body light pressure vary) Lympho- were seen between groups in
light pressure effleu- undergoing radia- effleurage massage. cytes changed cortisol levels.
rage on circulating tion therapy (30) Cold-pressed vegetable
lymphocytes, sali- oil was used. The effleu-
vary cortisol levels, rage technique used was
heart rate and blood strokes with both hands,
pressure in patients palms and fingers, using
with breast cancer light pressure (in average
0.0090 kg/cm2).
Provider: massage
trained clinician (nurse)
Comparator(s)
The control group was
given the same amount
of attention as the mas-
sage group but did not
receive massage.
Boylan (2005)79 In a pilot study USA, Clinical Non-RCT Women diagnosed The massage sessions (3 Cortisol (uri- There were large variances in
massage resulted in in the previous 3 x 30 minutes each week nary) Serotonin the urine results. Positive
women with breast years with early for 5 weeks). The thera- (urinary) Epi- changes (increases) were bene-
cancer reporting stage (I-III) breast pists were instructed to nephrine (uri- ficial for dopamine and sero-
reduced anxiety, cancer. Women restrict any talking dur- nary) Norepi- tonin. Only the increases in
depression and were not admitted ing the sessions to only nephrine (uri- dopamine and serotonin in the
anger, increased uri- into the study questions concerning nary) Dopa- massage group were statisti-
nary dopamine and until 3 months pressure and tender mine (urinary) cally significant.
serotonin, increased post-surgery and/ points. The massage was
natural killer {NK) or had completed a full body massage.
cells and lympho- their last radia- Provider: trained mas-
cytes. Thus, this tion and/or che- seuse
study was designed motherapy ses- Comparator(s)
to determine sion. (58) (1) Relaxation group
whether it was practised progressive
indeed massage, or muscle relaxation, 3 ses-
just simple relaxa- sions each week for 5
tion, that provided weeks.
the benefits in the (2) Control group only
pilot study. seen at the start and the
end of the 5 weeks
study.

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SYSTEMATIC REVIEW F. Kerr et al.

(Continued)
Citation Study aims Setting Study Type Population (N ¼ ) Intervention Outcomes Key findings

Chang et al. To investigate a Taiwan, Lab Non-RCT Healthy volun- Hand massage. Three Neural activity There are was a comparison
(2012)130 subject’s EEG per- teers, mainly col- minute circular massage (EEG) around EEG coherence during
formance under lege students (24) for each of 4 acupoints massage sessions between the
massage treatment in the mid shoulder area. hands-on group and mechani-
applied by hand and Provider: trained mas- cal massage group. The coher-
treatment applied seuse ence value is higher when
by mechanical Comparator(s) channel pair distance is
devices The same as the inter- greater. This is valid for both
vention but subjects groups. Second, the coherence
massaged themselves value of the hands-on group is
with a mechanical averagely higher than that of
device. the same channel pairs for the
mechanical massage group.
The hands-on group’s coher-
ence does not change signifi-
cantly during the massage
session, but the mechanical
massage group’s coherence
becomes lower, especially with
regard to alpha and beta
rhythms. Massage by hand
seems to maintain EEG chan-
nel coherence, while massage
by mechanical may interrupt
the original brain interaction
between different brain
regions. For left-right symme-
try coherence, P3-P4 pair is
the lowest coherence value
pairs for both groups. Similar
with around coherence, there
were more significant varia-
tions on theta, alpha, and beta
rhythms for mechanical mas-
sage than for hands-on mas-
sage, and there was a
significant massage stage-type
interaction on beta rhythm.
Cong, Luding- This study tested USA, Clinical RCT Male and female Study 1 KC for 80 min- Cortisol (sali- 30 minutes of KC before and
ton-Hoe & KC effects on bio- preterm infants at utes, after 60 minutes vary and throughout heel stick
Walsh (2011)80 behavioral responses 30–32 weeks’ GA baseline data was col- serum) appeared to be effective in
to heel stick in pre- and 2–9 days’ lected and then KC con- reducing bio-behavioural pain
term infants (30–32 postnatal age (28) tinued for 20 minutes responses and cortisol levels in
weeks’ gestational Study 2 KC for 30 min- preterm infants. Changes in
age, 2–9 days old) utes, after 10 minutes these outcomes were not seen
measured by Prema- baseline data was col- for 80 minute KC.
ture Infant Pain Pro- lected and then KC con-
file and salivary and tinued for 20 minutes
serum cortisol. The Provider: mother
paper reports two Comparator(s)
pilot studies. Control group: Infants
remained in the Incuba-
tor for the procedure.
They were left undis-
turbed for the same time
as the KC.
de Cássia To evaluate the Brazil, Clini- Pre-test post- Healthy infants Infants received two Cortisol (sali- Cortisol levels increased after
Fogaça et al. levels of salivary cal test aged 4–6 months standard 15 minute vary) the two consecutive days and
(2005)81 cortisol before and (9) Shantala massages on were still raised after one
after Shantala mas- two consecutive days week. The differences were
sage therapy on and then after a one only statistically significant
healthy infants week interval in the for the afternoon measures.
morning and the after-
noon
Provider: researcher

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SYSTEMATIC REVIEW F. Kerr et al.

(Continued)
Citation Study aims Setting Study Type Population (N ¼ ) Intervention Outcomes Key findings

Ditzen et al. The authors hypoth- Switzerland, RCT Healthy, hetero- Standardized physical Cortisol (sali- Women with positive physical
(2007)127 esized that standard- Lab sexual women, contact (i.e., instructed vary) Oxytocin partner contact before stress
ized physical aged 20–37 years, neck and shoulder mas- (plasma) exhibited significantly lower
partner contact who had been sage, no conversation) cortisol and heart rate
(neck and shoulder married or coha- for 10 minutes from responses to stress but no
massage) results in biting with a sig- spouse 5 minutes prior different plasma oxytocin
attenuated responses nificant other for to Trier Social Stress levels compared to women
of the hypotha- at least 12 Test (5 minute public who received social support or
lamic–pituitary– months (67) speaking task and then 5 no social interaction. Verbal
adrenal axis and the minute mental arithmetic social support alone was not
autonomic nervous task in front of a panel). associated with reduced stress
system to acute psy- Provider: spouse responsiveness.
chosocial stress in Comparator(s)
women. (1) Social support (i.e.,
only verbal support from
spouse) for 10 minutes
from spouse 5 minutes
prior to Trier Social
Stress Test (2) No spou-
sal support (left alone)
for 10 minutes 5 minutes
prior to Trier Social
Stress Test
Donoyama, To use scientifically Japan, Lab Non-RCT Fifteen healthy 40-minute Anma therapy Cortisol (sali- Salivary cortisol concentration
Munakata & valid parameters to female volunteers session after a 15 minute vary) was reduced only marginally
Shibasaki determine the effect in their fifth rest and assessment. after Anma therapy sessions.
(2010)119 of Anma therapy on decade (15) Standard therapy of
both the body and kneading, stroking and
mind pressing, with comfort-
able intensity over whole
body. Five sessions over
2 and a half consecutive
weeks.
Comparator(s)
same as for the Anma
therapy group, but parti-
cipants rested for 40
minutes instead.
Donoyama & To examine how Japan, Lab RCT Females in the 40 minutes Anma Ther- Cortisol (sali- For concentration levels of
Shibasaki differences in mas- fifth decade of life apy (whole body vary) salivary cortisol, post-inter-
(2010)120 sage practitioners’ with chronic mus- through clothing, using vention values were signifi-
proficiency impacted cle stiffness kneading, stroking and cantly lower than those
clients physically around the neck pressing). obtained pre-intervention;
and psychologically, and shoulders. (8) Provider: trained mas- however, there were no signif-
as measured by cor- seuse icant differences among the
tisol, pain (visual Comparator(s) four interventions.
analogue score), (1) Intervention adminis-
anxiety (State-Trait tered by 1st year student
Anxiety Inventory) of massage and acupunc-
ture (2) Intervention
administered by 2nd
year student (3): Rest on
massage table
Donoyama, To determine the Japan, Non-RCT Intervention ¼ 3 15 minute rest followed Cortisol (sali- Marginal decreases for corti-
Shoji & Muni- effect of Anma ther- Clinical patients, 51–74 by 40 minutes Anma vary) sol in Anma group. Results
kata (2005)82 apy on both the years with a vari- Therapy (whole body were considered inconclusive
body and mind. ety of diagnosis through clothing, using due to study design, particu-
Impact on Cortisol Non-inter- kneading, stroking and larly differences between
s-IgA, Pain (visual vention ¼ 3 pressing), twice a week groups and small sample size.
analogue score), ‘healthy’ college for 2 and half weeks.
anxiety (State-Trait students, 22–43 Five sessions in total.
Anxiety Inventory). years with a mus- Provider: not stated
culoskeletal (MS) Comparator(s)
injury (6) Same as for intervention
group except Anma was
replaced with resting on
the bed for the same
period.

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SYSTEMATIC REVIEW F. Kerr et al.

(Continued)
Citation Study aims Setting Study Type Population (N ¼ ) Intervention Outcomes Key findings

Elverson et al. To explore relation- USA, Clinical Correlational Mothers and their Behaviors of 46 mothers Cortisol (sali- A higher percentage of obser-
(2012)83 ships between study term transitional and their term transi- vary) vations in which mother was
selected social regu- newborn infants tional newborn infants holding infant was related to
lation behaviors (46 dyads) were measured with the lower infant total cortisol dur-
(holding and feed- Index of Mother-Infant ing the first 6 hours after
ing) and the transi- Separation. For each birth.
tional newborn infant, eight unique ran-
infant’s cortisol dom times for Index of
response during the Mother–Infant Separa-
first 6 hours after tion observations during
birth. each of the 6 hours after
birth (total of 48 obser-
vations) were under-
taken. The first saliva
sample was collected at
15 to 45 minutes of age,
except after cesarean
births when saliva was
collected as soon as pos-
sible after the mother
and infant returned to
the labor–delivery–
recovery room (n ¼ 10,
22% of sample, oldest
was 82 minutes of age).
Subsequent saliva sam-
ples were obtained at
2 hours (15 minutes)
and 6.5 hours (15 min-
utes) after birth. In addi-
tion, saliva samples were
collected before the bath
(after admission to the
nursery) and 20 to 30
minutes after the begin-
ning of the initial bath.
Feldman, Singer To measure the Israel, Lab RCT Mothers and their Fifty-three dyads were Cortisol (sali- Cortisol reactivity was higher
& Zagoory effects of touch on infants (53 dyads) tested in two paradigms: vary) Vagal among infants in the SF con-
(2010)128 infant stress reactiv- still-face (SF) and still- tone (Vna) dition. In the recovery phase,
ity during simulated face with maternal touch Oxytocin cortisol decreased for infants
maternal depriva- (SFþT). Maternal and (serum) in the SFþT, and it markedly
tion infant cortisol levels increased for those in the SF.
were sampled at base- Vagal tone showed a greater
line, reactivity, and suppression when SF was not
recovery and mother’s accompanied by maternal
and infant’s cardiac touch. In reunion phase, Vna
vagal tone were mea- in touch condition recovered
sured during the free to free play level, but in no-
play, still-face, and touch, remained same as SF.
reunion episodes of the Touch synchrony during free
procedure. play was associated with
higher infant vagal tone, not
cortisol. Touch myssynchrony
– maternal tactile stimulation
while the infant gaze averts –
correlated with higher mater-
nal and infant cortisol and
higher gaze aversion, and
lower infant Vna during free
play.
Field et al. To examine the USA, Clinical RCT Children and ado- 52 subjects received a 30 Cortisol In the short term, to 30 min-
(1992)89 independent effects lescents hospital- minute back massage per (saliva), Corti- utes follow-up there was a
of massage on the ized for day for 5 days. sol (urine), nor- decrease in salivary cortisol
behaviors of chil- depression or Provider: psychology stu- epinephrine, only. Salivary cortisol did not
dren and adoles- adjustment disor- dents epinephrine and change over the 5 day period
cents hospitalized ders (72) Comparator(s) dopamine but both urinary cortisol and
for depression or 20 subjects received a urine norepinephrine did
adjustment disorders videotape viewing for decrease over the 5 day
the equivalent time period.

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SYSTEMATIC REVIEW F. Kerr et al.

(Continued)
Citation Study aims Setting Study Type Population (N ¼ ) Intervention Outcomes Key findings

Field & Grizzle To compare the USA, Clinical RCT Depressed adoles- The massage therapy Cortisol Lower salivary cortisol levels
(1996)86 effects of massage cent mothers who subjects (N ¼ 16) (salivary and after massage therapy (no
and relaxation ther- had recently given received a 30-minute urinary) effect for the relaxation
apies on anxiety birth at a large massage per day on two group); and lower urine corti-
and depression in a inner-city hospital consecutive days per sol levels on the last day
sample of depressed and were week for five consecutive versus the first day of massage
adolescent mothers recruited from the weeks (10 massages). therapy (no effect for the
hospital’s mater- Provider: trained relaxation group). Only the
nity ward (32) masseuse massage therapy group
Comparator(s) showed lower stress hormone
The relaxation therapy (cortisol) levels after their ses-
subjects (N ¼ 16) spent sions. In addition, only the
the same amount of time massage therapy group experi-
in relaxation therapy as enced a reduction in depres-
the massage therapy sub- sion and in stress (as
jects spent in MT. The manifested by their lower uri-
first 15 minutes con- nary cortisol levels) across the
sisted of yoga exercises. course of the study.
The second 15-minute
segment consisted of
progressive muscle
relaxation.
Field et al. To assess the effects USA, Clinical RCT Depressed women Massage group received Newborn corti- Massage group neonates had
(2009)84 of pregnancy mas- recruited between 2 moderate pressure sol (salivary) lower cortisol levels. The mas-
sage by significant 16 and 20 weeks massages per week for a Maternal corti- sage group mothers had lower
others on prenatal gestation from period of 12 weeks. sol (salivary) cortisol levels (M ¼ 128.6
measures as well as two ultrasound Provider: significant versus 2328.8,
perinatal outcomes clinics. Primarily others who were taught F ¼ 4.17,p ¼ .05). Newborns
low socioeco- the massage by a mas- of the massaged mothers also
nomic status. sage therapist and were had lower cortisol levels than
20% met criteria given DVDs for at-home the newborns of the control
for major depres- coaching in the massage mothers.
sive disorder. procedure.
(129) Comparator(s)
Control group: standard
treatment
Field et al. To assess a more USA, Clinical RCT Depressed preg- Two 20-minute massages Cortisol (uri- A group by first/last day inter-
(2004)85 cost-effective form nant women 8– per week over 16 weeks. nary) Catecho- action effect showed that the
of massage therapy, 24 weeks gesta- Provider: Trained mas- lamines (norepi- massage therapy group experi-
namely having the tion recruited sage therapists taught nephrine, epi- enced the following effects: i)
‘‘significant other’’ from obstetric the massage to the ’’sig- nephrine, dopa- increased serotonin levels; ii)
instead of a massage and gynaecology nificant others’’ of the mine) (urinary) decreased cortisol levels; iii)
therapist provide clinics. Of middle women. Serotonin (uri- increased dopamine levels;
the massage socio-economic Comparator(s) nary) and iv) decreased norepineph-
status (112) (1) Progressive muscle rine levels.
relaxation comparison
group
(2) Standard prenatal
care only group (3)
Group of 28 non-
depressed women
Field, Grizzle To evaluate the USA, Clinical RCT 40 full-term I-to- Massage-therapy infants Cortisol (sali- Salivary cortisol levels
et al. (1996)87 potential benefits of 3-month old were provided a 15 min- vary and uri- decreased in the massage
massage therapy for infants born to ute massage midway nary) Norepi- group during the massage
healthy infants who depressed adoles- between morning feed- nephrine (Uri- unlike the rocking group
were born to cent mothers (40) ings 2 days per week for nary) Epineph- infants whose cortisol levels
depressed mothers 6 weeks. The therapist rine (urinary) remained the same. Over time
placed a small amount Serotonin (uri- (comparing day 1 and day
of mineral baby oil on nary) 12), the massage group expe-
the palms of her warm rienced decreases in urinary
hands and placed her catecholamine and cortisol
hands on the infant’s levels and increased serotonin
chest then worked on six levels. Increased soothability
regions of the infant’s and decreased stress levels, as
body. suggested by lower cortisol
Provider: researcher and catecholamine levels, may
Comparator(s) have contributed to the
The rocking group: Dur- infants’ enhanced responsivity.
ing this condition, the
infant was held in a
cradled position by the
researcher and rocked in
a rocking chair.

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SYSTEMATIC REVIEW F. Kerr et al.

(Continued)
Citation Study aims Setting Study Type Population (N ¼ ) Intervention Outcomes Key findings

Field, Ironson To investigate the USA, Clinical RCT Medical faculty Chair massage: 15 min- Cortisol (sali- Salivary cortisol levels were
et al. (1996)88 effects of massage and staff members utes a day, 2 days a vary) lower following the massage
on alertness as mea- (80% females, M week for 5 weeks, and Neural activity but not the control sessions
sured by EEG and age ¼ 26). (50) the sessions were sched- (EEG) but only on the first day (a
by speed and accu- uled at noon each day. repeated measures by group
racy of performance Standard Swedish mas- interaction effect revealed a
on math computa- sage procedure (knead- decrease in salivary cortisol
tions. In addition, ing of muscles) was levels on the first day for the
anxiety, depression used. massage group and an
and cortisol levels Provider: trained mas- increase on the last day for
were expected to seuse the relaxation control group).
decrease. Comparator(s) No effect on cortisol was
Relaxation control observed after 5 weeks of
group: The subjects were massage.
asked to relax by tight-
ening and relaxing the
same body parts as those
that were massaged for
the massage therapy
group (and in the same
sequence).
Field et al. Massage therapy USA, Clinical RCT Patients with burn Standard care and a 20 Cortisol (sali- On both days the salivary
(1998)90 was expected to injuries at a Burn minute massage once a vary) cortisol levels decreased after
reduce stress hor- Center (28) day for 1 week. Massage massage in the massage group
mones in patients took place just before but there was no difference in
with burns injuries debridement. Massage the control group. Salivary
before debridement was delivered in a supine cortisol (measured before the
then prone position. massage) was lower after the
Provider: trained mas- 5 day period than before.
seuse
Comparator(s)
Usual care plus 20 min-
utes of sitting and relax-
ing.
Fujita et al. To evaluate the Japan, Clini- Non-RCT Mothers who had Baby massage (stroke Cortisol (sali- No significant differences in
(2006)91 effects of baby mas- cal just given birth and/or massage each vary) salivary cortisol levels between
sage on mothers’ (39) area of the babies’ body; groups, however, salivary cor-
mood status and legs, belly, chest, arms, tisol did increase in the con-
salivary cortisol and back). At least 10 trol group and decrease in the
level within 3 minutes/day until 3 massage group over time.
months after deliv- months after delivery.
ery Provider: mother
Comparator(s)
Control group (no mas-
sage)
Garner et al. To examine the Australia, Non-RCT Young adult psy- MT consisted of a 20 Cortisol (sali- No differences in cortisol
(2008)92 effectiveness of a Clinical chiatric inpatients minute massage therapy vary) levels between groups over-
relaxation massage aged 15–25 years session offered daily to time. There were some imme-
therapy programme (32) patients during their diate effects of massage on
in reducing stress, period of hospitalization. cortisol. Following the 20
anxiety and aggres- Natural massage balm minute massage therapy ses-
sion on a young containing no essential sion there was a significant
adult psychiatric oils or scent, was applied reduction in saliva cortisol
inpatient unit. to forearms and hands. levels at both the initial and
Measures were taken at final massage therapy session.
baseline and follow-up
(after conclusion of 7
weeks) and just before
and immediately follow-
ing both the first and
last massage sessions.
Provider: trained mas-
seuse
Comparator(s)
Treatment as usual

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SYSTEMATIC REVIEW F. Kerr et al.

(Continued)
Citation Study aims Setting Study Type Population (N ¼ ) Intervention Outcomes Key findings

Gitau et al. To determine the USA, Clinical Non-RCT Clinically stable 20 minute skin-to-skin Cortisol Control: No significant
(2002)93 effects of a 20 min- preterm babies no over 2 consecutive days. (salivary) change in cortisol over time
ute intervention of longer requiring The mother was seated Massage group: no significant
maternal skin-to- intensive care sup- on a standard rocking change overall Skin-to-skin
skin contact, mas- port and within 4 chair, tilted at an angle contact: there was a reduction
sage, or a control weeks of birth in of approximately 608. in saliva cortisol, and the
period, on stress (as a low dependency Provider: mother overall reduction for the
measured by sali- unit (40) Comparator(s) whole group was highly
vary cortisol) of (1) 20 minute massage significant.
pre-term babies consisted of gentle mas-
sage of the trunk and
limbs using rachis oil.
Massage was carried out
at a particular time of
day, independent of the
state of the baby. (2)
Control group
Gordon et al. To determine Israel, Home Correlational Cohabitating par- Families were visited at Triadic syn- Among mothers, OT was an
(2010)94 impact of oxytocin study ents and their home twice during the chrony: independent positive predictor
(OT) and salivary healthy firstborn evening hours (4–8 PM). Moments of and cortisol (CT) was an inde-
cortisol (CT) on tri- infant (37) Interactions were video- coordination pendent negative predictor of
adic synchrony. taped between each par- between physi- triadic synchrony. For fathers,
ent and the child. On cal proximity only OT independently pre-
the second home visit, and affectionate dicted triadic synchrony and
families were videotaped touch between no relations were found
in a free-play triadic the parents as between paternal CT and syn-
interaction. Parents were well as between chrony in the family triad,
instructed that the two parent and indicating that higher paternal
of them play together infant while OT predicted higher levels of
with the infant as they both parent triadic synchrony
normally do and no spe- and child are
cific position or toys synchronizing
were required. their social gaze
Grewen et al. To examine whether USA, Lab Pre-test post- Healthy couples Baseline: Partners were Oxytocin Cortisol levels were lower
(2005)111 the magnitude of test living with their seated in comfortable (plasma) Corti- after WC than before it in
plasma oxytocin current spouse or chairs in separate rooms. sol (plasma) both men and women. How-
(OT), norepineph- monogamous Warm contact: Couples Norepinephrine ever, there were no differences
rine (NE), cortisol, partner for at were seated on a love- (plasma) in cortisol between subjects
and blood pressure least 1 year (76) seat in a quiet room and reporting high versus low
(BP) responses instructed to sit close partner support.
before and after a together, holding hands Individuals reporting high
brief episode of if they felt comfortable versus low partner support
warm contact (WC) doing so. They were exhibited greater OT across
with a spouse/part- asked to talk about a the protocol (between sub-
ner may be related time they had spent jects). There were significantly
to the strength of together that made them greater mean OT levels in the
perceived partner feel closer as a couple (2 high versus low partner sup-
support. minutes). They then port groups at all measure-
watched a 5-minute seg- ment times. The link between
ment of a romantic greater partner support and
video they had previ- higher OT values was
ously seen. They then observed in men and women
were instructed to talk at baseline and was present
for 2 minutes about a after WC with partner in
time when they felt close women (postcontact rest alone
as a couple. At the end minute 4). When baseline OT
of this session, partners was examined by partner sup-
stood for a 20-second port quartiles, a consistent
hug. pattern of increasing OT with
Provider: partner Post- increasing partner support
contact: Subjects were was seen.
moved to separate cham- Although there were no links
bers to rest quietly alone between greater partner sup-
for 10 minutes. port and lower diastolic blood
pressure, heart rate, NE, or
cortisol, correlations of higher
OT with lower systolic blood
pressure, diastolic blood pres-
sure, and NE were obtained.
These associations were seen
in women but not men.

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(Continued)
Citation Study aims Setting Study Type Population (N ¼ ) Intervention Outcomes Key findings

Hernandez-Reif To examine massage USA, Clinical RCT Women with Received 15 massages Norepinephrine Cortisol stress hormone, nor-
et al. (2004)95 therapy for women Stage 1 or 2 during the study period (urinary) Epi- epinephrine, and epinephrine
with breast cancer breast cancer (three massages each nephrine (uri- levels did not decrease follow-
for i) improving diagnosis within week for 5 weeks). Each nary) Cortisol ing massage therapy. How-
mood and biological the past 3 years massage was 30 minutes (urinary) Dopa- ever, for the massage therapy
measures associated and at least 3 long and consisted of mine (urinary) group there was an increase in
with mood enhance- months post-sur- Swedish, trager, and acu- Urinary 5- (1) dopamine, and (2) seroto-
ment (serotonin, gery, chemother- pressure techniques. The Hydroxyindo- nin levels, from the first to the
dopamine), ii) apy, and/or massages were con- leacetic acid (a last day. The control group
reducing stress and radiation therapy ducted in a quiet and metabolite of showed a significant increase
stress hormone (34) private room on a mas- serotonin) in norepinephrine.
levels, and iii) sage table.
boosting immune Provider: trained mas-
measures seuse
Comparator(s)
Control group: standard
medical care alone.
Hietanen et al. We aimed to deter- Finland, Lab Non-RCT Adults with nor- Participants viewed a EEG activity Measurements of hemispheric
(2008)132 mine whether seeing mal or corrected- face/gaze stimulus and a (power in the asymmetry in the frontal EEG
another person’s to-normal vision control object (a radio) alpha band) activity indicated that another
direct vs. averted (20) in four different condi- Skin conduc- person’s direct gaze elicited a
gaze has an influ- tions factorially manipu- tance responses relative left-sided frontal EEG
ence on the obser- lating the gaze/object activation (indicative of a ten-
ver’s neural direction (direct and dency to approach), whereas
approach-avoidance averted) and the stimu- averted gaze activated right-
responses. We also lus–presentation mode sided asymmetry (indicative of
examined whether it (picture and live). The avoidance). Skin conductance
would make a dif- pictures were presented responses were larger to faces
ference if the parti- on a computer monitor, than to control objects and to
cipants were whereas the live stimuli direct relative to averted gaze.
looking at the face were presented through Gaze direction also influenced
of a real person or a a liquid crystal shutter. subjective ratings of emotional
picture. Provider: researchers arousal and valence. However,
Comparator(s) all these effects were observed
Two small, portable only when participants were
radios (presented in pic- facing a real person, not when
ture and live) looking at a picture of a face.
Holt-Lundstad, To investigate the USA, Lab RCT Healthy married Couples underwent one Oxytocin There was no main effect of
Birmingham & impact of warm couples (68) session of training in lis- (plasma and the intervention on salivary
Light (2008)112 touch enhancement tening-touch based on salivary) Corti- cortisol, or plasma OT, how-
on plasma oxytocin, the types of touch used sol (salivary) ever, there was a significant
24-hour ambulatory in Rosen Method Body- Alpha amylase effect of the intervention for
blood pressure, and work and one training salivary OT obtained at home
salivary cortisol and session in head, neck, during the month of treat-
alpha amylase and shoulder massage. ment/monitoring. Even as
The intervention couples early as intervention week 1,
then practiced these salivary OT levels were signif-
warm touch techniques icantly higher in the interven-
for 30 minutes 3 times tion group than the control
per week for 4 weeks. group. Both men and women
Provider: partners in the intervention condition
Comparator(s) continued to have higher OT
Behaviour monitoring levels than those in the moni-
control group: Subjects toring control condition dur-
were told not to change ing the final week. This effect
anything about their remained significant after
normal behaviour with adjusting for pre-treatment
their spouse and to sim- plasma OT and even after
ply keep a diary of their adjusting for their higher
physical affection and week 1 OT levels, indicating
mood. that further significant albeit
modest increases in OT activ-
ity occurred with greater
exposure to the warm touch
intervention. After controlling
for pre-treatment levels, post-
treatment alpha amylase was
significantly lower among hus-
bands and wives in the inter-
vention group than those in
the control group.

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SYSTEMATIC REVIEW F. Kerr et al.

(Continued)
Citation Study aims Setting Study Type Population (N ¼ ) Intervention Outcomes Key findings

Im & Kim To test the effect of South Korea, Non-RCT Pre-term infants Yakson: 15 minutes Cortisol (uri- Following the intervention
(2009)96 Yakson and Gentle Clinical with a gestational twice a day for 15 days. nary) Norepi- period, infants in the Yakson
Human Touch age of 26–34 Yakson consists of three nephrine (uri- and GHT groups had signifi-
(GHT) on preterm weeks at birth 5-minute phases: resting nary) cantly lower stress hormone
infants’ stress and (59) the hand on the infant, levels compared to the control
behaviours com- gentle caressing, and group infants. No significant
pared to usual nurs- resting the hand again. difference was found in stress
ing care Provider: massage hormone levels between Yak-
trained clinicians (nurse) son and GHT group infants.
Comparator(s)
(1) GHT: 15 minutes
twice a day for 15 days.
GHT consists of hand
resting for 15 minutes.
(2) Control group: usual
care.
Ironson et al. To examine the USA, Lab Mixed design HIVþ and HIV- 45 minute daily mas- Cortisol (uri- There was a significant
(1996)113 effects of daily mas- including pre- gay men with no sage. nary and sali- decrease in urinary cortisol,
sage for one month test post-test AIDS-defining Provider: trained mas- vary) Norepi- during the massage period and
on the immune and crossover symptoms. If on seuse nephrine (uri- a marginally significant
function of HIVþ for part of the Antiretroviral Comparator(s) nary) Epineph- increase during the control
and HIV- gay men sample therapy, had to Control (no massage) rine (urinary) period. For catecholamines
have been on during the massage period, the
them for at least change was not significant.
3 months. (29)
Jung et al. To evaluate differ- South Korea, RCT Men aged 20–35 Qi no touching (QTN): Cortisol No significant differences
(2006)122 ences in the effects Lab years (women The subjects received (plasma) between the effects of Qi ther-
of Qi therapy with- were not included QTN for 10 minutes apy with and without touch-
out touching or because of their according to the proce- ing. There were significant
with touching on hormonal varia- dures described in the effects on anxiety, alertness,
anxiety, mood, neu- tions) (24) standard sequence. The depression, fatigue, tension,
rohormones, and Qi master’s hand is cortisol levels, and NK cell
cellular immune moved about 3–10 cm cytotoxicity for both QTN
function from the body in a pat- and QTT, and on neutrophil
tern from the head to function for QTN only. These
the toes. When a subject findings suggest that there are
arrived for the experi- few differences between the
ment, he was taken to effects of QTN and QTT.
the experimental room
and seated on a bed.
After 5 minutes rest
(Pre), the subject
received Qi. Qi therapy
was followed by 10 min-
utes of rest (Post I).
Provider: trained mas-
seuse
Comparator(s)
Qi touching (QTT):
Administered by the
same Qi master, who
pressed several impor-
tant acupoints with
effort or intention to
insert Qi through them.
Kim et al. To examine the USA, Lab Pre-test post Non-clinical sam- The Modified Still Face Oxytocin The mother’s oxytocin
(2014)125 relationship between test ple of first-time Procedure (MSFP) is a (plasma) response was positively associ-
maternal oxytocin mothers (50) three-phase procedure, ated with the duration of time
response and during which the mother her gaze was directed toward
mother-to-infant interacts freely with the her infant, while negatively
gaze during periods infant in Phases 1 and 3, associated with the frequency
of infant non-dis- but is instructed to with which her gaze shifted
tress as well as dis- maintain a neutral ‘still away from her infant. Impor-
tress. Two patterns face’ during Phase 2, tantly, these associations were
of maternal gaze, suddenly depriving the more pronounced under con-
maternal gaze infant of maternal con- ditions of infant distress than
toward and gaze tingency and inducing non-distress. Mothers who
shifts away from the stress in the infant. The showed low/average oxytocin
infant, were micro- MSFP thereby offers an response demonstrated a sig-
coded while mothers opportunity to examine nificant decrease in their
interacted with their the mother’s behavior in infant gaze during periods of
7-month-old infants the absence and presence infant distress, while such
during a modified of signals of infant dis- change was not observed in
still-face procedure. tress. mothers with high oxytocin
response.

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(Continued)
Citation Study aims Setting Study Type Population (N ¼ ) Intervention Outcomes Key findings

Kim, Kim & A scalp massage South Korea, RCT Female office Scalp massage was per- Epinephrine In this study, 15-minute and
Ko (2016)123 was conducted on Lab workers, aged formed for 15 minutes/ (plasma) Nor- 25-minute scalp massages had
female office work- between 20–49 session for experimental epinephrine a significant effect on norepi-
ers divided into a years (34) group (I) (plasma) Corti- nephrine and cortisol while
15 minute group Provider: trained sol (plasma) the 25-minute scalp massage
and 25 minute masseuse had a significant effect on
group and its effect Comparator(s) epinephrine. This suggests that
on stress hormone, (1) 25 minutes/session a scalp massage decreases the
blood pressure and for experimental group activation of the sympathetic
heart rate was ana- (II), twice a week, for a nerve while increasing the
lyzed in order to total of 20 times over 10 activation of the parasympa-
provide a theoretical weeks in both groups. thetic nerve, resulting in a
rationale to apply (2) Control group: no decrease in the secretion of
scalp massage as massage norepinephrine and cortisol,
stress therapy or in other words, stabiliza-
tion of hormone levels.
Kramer et al. To ascertain USA, Clinical Non-RCT Premature infants Extra tactile stimulation: Cortisol Plasma cortisol levels revealed
(1975)97 whether touch, in with a gestational gentle, non-rhythmic (plasma) no significant difference
the form of extra age of 38 weeks stroking of the greatest between the two groups. An
tactile stimulation, or less (14) possible area of skin sur- inspection of the means and
would result in face of the infant’s body standard deviations, however,
more rapid physical by the nurse’s hand for a indicated that they were going
and social develop- total of 48 minutes a in the right direction (i.e., a
ment and a greater day and for a minimum decrease in cortisol in the
degree of social of two weeks while the extra tactile stimulation
development of the infant was confined to group).
premature infant an isolette (the 48 min-
utes was additional to
other tactile stimulation
provided in the usual
course of premature
infant care)
Provider: massage
trained clinician (nurse)
Comparator(s)
Control group: no extra
tactile stimulation
Kuhn et al. To investigate the USA, Clinical RCT Preterm infants Tactile-kinesthetic stimu- Dopamine (uri- Urine norepinephrine and epi-
(1991)98 neuroendocrine (mean gestational lation for three 15-min- nary) Norepi- nephrine values increased sig-
response in preterm age 30 weeks, ute periods at the start nephrine (uri- nificantly only in the
infants to a pattern mean birth weight of 3 consecutive hours nary) Epineph- stimulated babies. Urine dopa-
of tactile-kinesthetic 1176 gm) (40) each day for 10 days. rine (urinary) mine and cortisol values
stimulation that Stimulation was con- Cortisol (uri- increased in both groups, and
facilitates their ducted at the end of a nary and serum growth hormone
growth and develop- sleep cycle, when infants plasma) decreased in both groups.
ment were awake but in a
state of quiet rest. The
stimulation session com-
prised of three standard-
ized 5-minute phases.
The first and third
phases were tactile stim-
ulation; the second phase
was kinesthetic stimula-
tion. For tactile stimula-
tion, the infant was
placed in the prone posi-
tion. The infant was
stroked with the flats of
the fingers of both hands
for five 1-minute seg-
ments over each region
of the body. For kines-
thetic stimulation, the
infant was placed in a
supine position. Each
five 1-minute segment
consisted of six passive
flexion-extension
motions lasting approxi-
mately 10 seconds each.
Each 1-minute segment
involved a different body
part.
Provider: not stated
Comparator(s)
Normal nursery care

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(Continued)
Citation Study aims Setting Study Type Population (N ¼ ) Intervention Outcomes Key findings

Light, Grewen To examine the USA, Lab Pre-test post- Premenopausal Baseline: Women were Oxytocin Participants were grouped into
& Amico relationships test women aged 20– seated alone in a room (plasma) Blood 3 categories: those with low,
(2005)114 between self- 49-years old (59) separated from their pressure (BP) medium and high baseline
reported frequency partners. Heart rate OT. The low OT group had
of partner hugs, Warm contact: Couples (HR) Mean significantly higher SBP, DBP
plasma OT and BP were seated on a love- arterial pressure and MAP at baseline than the
levels in premeno- seat in a quiet room and (MAP) Fre- high OT group. The low OT
pausal women instructed to sit close quency of phys- group had significantly higher
before and after together, holding hands ical affection baseline SBP than the moder-
warm contact with if they felt comfortable (Physical Affec- ate OT group. During the
their husbands/part- doing so. They were tion Scale, PAS) stressor periods (speech prepa-
ners ending with asked to talk about a Partner Support ration, active speech and post-
hugs. Tested time they had spent (Social Rela- speech recovery), the OT
whether OT activity together that made them tionships Index, groups no longer differed sig-
may be a partial feel closer as a couple (2 SRI) nificantly in BP or HR
mediator of the minutes). Next they although there was a tendency
expected relation- watched a 5-minute seg- for the High OT group to
ships between ment of a romantic maintain the lowest mean BP
greater Partner video they had previ- levels across events. OT group
Hugs and lower car- ously seen. They then differences in baseline HR
diovascular were instructed to talk were also seen. The low OT
responses. again for 2 minutes group had significantly higher
about a time during baseline HR than the high OT
which they felt especially or the moderate OT groups.
close as a couple. Cou- Greater frequency of Partner
ples were left alone, Hugs and Partner Massages
unmonitored and unob- were associated with higher
served except when the baseline OT level; other PAS
experimenter entered the items (kissing, hand-holding,
room to give instruc- sitting/lying close) were not
tions. At the end of this reliably correlated with any
session partners stood OT measure. Higher SRI score
for a 20 second hug. was not significantly associ-
Provider: partner Post- ated with higher baseline OT.
contact stressor: Women Partner Hugs was consistently
were immediately sepa- unrelated to OT levels
rated from their part- obtained during speech prepa-
ners. The stressor ration, active speech or recov-
involved 2 minutes of ery. Thus, only baseline OT
task instructions, fol- was a potential candidate as a
lowed by 3 components: mediator of the Partner Hugs
(1) silent speech prepara- link to lower BP. Baseline OT
tion (2 minutes), (2) giv- served as a significant partial
ing a tape-recorded mediator of the effect of Part-
speech about a recent ner Hugs on baseline SBP and
interpersonal event (one MAP, and a marginally signif-
not involving their part- icant mediator of the effect of
ners) that made the Partner Hugs on baseline DBP
woman feel angry or and speech preparation DBP.
stressed (3 minutes), and
(3) post-speech recovery
while listening to a
replay of their own tape
recorded speech (3 min-
utes).
Lindgren et al. To report and eval- Sweden, Clin- RCT Patients scheduled After baseline measure- Cortisol No significant differences in
(2013)99 uate a complex ical for elective aortic ments, all subjects were (plasma) concentration of serum corti-
touch massage inter- surgery (20) exposed to an experi- sol between groups
vention according to mental stressful situation
the British Medical (Trier Social Stress
Research Council Test,). Intervention
framework. This group received one
study aimed to eval- Touch Massage interven-
uate the effects of tion performed on the
touch massage on hands, arms, feet and
levels of anxiety and legs
physiological stress 3 randomised groups,
in patients sched- received a single massage
uled for elective aor- intervention of about 60
tic surgery. minutes including a 20-
minute rest period:
Provider: massage
trained clinicians (nurse)
Group 1: rhythmical
massage Group 2: RM
with aroma oil Group 3:
RM with a neutral oil
Plus a control group

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SYSTEMATIC REVIEW F. Kerr et al.

(Continued)
Citation Study aims Setting Study Type Population (N ¼ ) Intervention Outcomes Key findings

Lindgren et al. To evaluate the Sweden, Clin- RCT crossover Healthy volun- Intervention Group Cortisol Saliva cortisol (hypothalamic–
(2010)100 short-term effects of ical design teers (22) received TM performed (salivary) pituitary–adrenal axis
tactile massage for 80 minutes in the activity) decreased signifi-
(TM) on stress following order: 20 min- cantly after intervention
response, as mea- utes each on the left
sured by heart rate hand, the right hand, the
(HR), heart rate right foot, and the left
variability (HRV), foot. A combination of
saliva cortisol levels, jojoba, sheabutter, sun-
and glucose metabo- flower, and vitamin E oil
lism in healthy was used in the massage.
volunteers, in order Participants in both
to test the hypothe- groups were shown to a
sis that TM reduces dark room with candles
stress response by and calm music and
increasing parasym- placed in the supine
pathetic nervous position. After the inter-
activity. vention in intervention
group or rest in control
group the participants
rested for additional 20
minutes.
Provider: massage
trained clinicians (nurse)
Comparator(s)
Control group (CG):
Participants rested in the
same setting but did not
receive TM.
Listing et al. To investigate the Germany, RCT 34 women diag- For a period of 5 weeks, Cortisol Cortisol serum levels
(2010)101 efficacy of classical Clinical nosed with pri- the intervention group (plasma) Sero- (p ¼ 0.03) were significantly
massage on stress mary breast (n ¼ 17) received tonin (plasma) reduced after massage therapy
perception and cancer (34) biweekly 30-minute clas- (T2) compared with baseline
mood disturbances, sical Swedish massages. in the intervention group.
as well as on seroto- Provider: trained mas- Serum cortisol level decreased
nin and cortisol seuse significantly from baseline to
serum levels. Comparator(s) the end of the intervention
For the same period, the period in the massage group
control group (n ¼ 17) (p ¼ 0.03) but increased again
received no additional at follow-up. There were no
treatment to their rou- significant changes in seroto-
tine health care nin in the massage or the
control group, nor between
the two groups, at the end of
the intervention and at follow
up.
Lovas et al. To identify and Australia, Single case 2 females in their Received a relaxing mas- Cortisol No significant difference in
(2002)131 assess the influence Lab ABAB time-lag 20s, biological sis- sage during the experi- (plasma) cortisol
of human touch, control ters, controlled mental phases (B) and
through massage for socioeconomic no massage during base-
therapy, on the difference (2) line phases (A). One
immune response of hour Swedish massage
healthy subjects with same masseuse in
uninterrupted, quiet
atmosphere.
Provider: trained mas-
seuse
Matthiesen To explore hand Sweden, Clin- Correlational Ten mothers who Infants whose mothers Oxytocin Periods of increased massage-
et al. (2001)102 movements and ical study had uncompli- had not been exposed to (plasma) like hand movements or suck-
sucking behavior in cated term preg- maternal analgesia were ing of the mother’s breast
healthy term new- nancies, and their video-recorded from were followed by an increase
borns who were infants (10) birth until the first in maternal oxytocin. When
placed skin-to-skin breastfeeding. Video pro- these movements decreased
on their mothers’ tocols were developed the oxytocin level usually
chests, and to study based on observations of went done except when the
maternal oxytocin the videotapes. Each infants started to suck. The
release in relation to infant’s hand, finger, change in the intensity of the
these behaviors mouth, and tongue infant’s stimulation of the
movements, positions of mother’s breast by ‘‘massage’’
the hand and body, and or sucking was significantly
sucking behavior were related to the change in
assessed every 30 sec- maternal oxytocin release.
onds.
Provider: newborn

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(Continued)
Citation Study aims Setting Study Type Population (N ¼ ) Intervention Outcomes Key findings

Mooncey et al. To assess the effect UK, Clinical Non-RCT Clinically stable, Skin-to-skin contact: On b-endorphin Both cortisol and b-endorphin
(1997)103 of mother-infant pre-term infants the first study day the (plasma) Corti- concentrations fell signifi-
skin-to-skin contact who were breath- infant lay prone in his or sol (plasma) cantly after the skin-to-skin
on plasma b-endor- ing spontaneously her cot or incubator, session. There was also a sig-
phin and cortisol (15) tilted at an angle of 30– nificant fall in cortisol levels
concentrations in 40 degrees, with no han- during the control session, in
stable, preterm dling for an initial 40 contrast to b-endorphin levels,
infants on a new- minute period. They in which there was no signifi-
born intensive care were undressed by their cant change. Analysis of vari-
unit mother and held nude ance showed that the fall in
for a 20-minute period b-endorphin, but not the fall
of maternal skin-to-skin in cortisol, during the skin-to-
contact between the skin session was significant
mother’s bare breasts, when compared with the con-
covered by the mother’s trol session. There was a wide
blouse and a light blan- variation in basal cortisol and
ket. The mother was b-endorphin levels on both
seated on a standard days.
rocking chair tilted at an
angle of approximately
608.
Provider: mother
Comparator(s) Infants
acted as their own con-
trols: On the second
study day, which served
as a control, the infant
was left unhandled
throughout the entire
study period of 60 min.
The infant remained
fully clothed in a crib or
incubator, lying prone at
an angle of 30–408.
Morhenn, Bea- To examine the USA, Lab RCT People from the Participants received 15 Oxytocin (OT) Massage was associated with
vin & Zak effect of massage on University of Cali- minutes of moderate (plasma) Adre- an increase in OT and reduc-
(2012)115 oxytocin and other fornia, Los pressure Swedish mas- nocorticotropin tions in ACTH, NO, and BE.
physiologic factors, Angeles (UCLA) sage on their upper hormone Comparing the effects of mas-
including adrenocor- (95) backs while lying prone (ACTH) sage for the massage group
ticotropin hormone on a massage table with (plasma) Beta- with those for the rest group,
(ACTH), nitric their clothes on and endorphin (BE) there were no significant dif-
oxide (NO), and shirts lifted to their (plasma) ferences between groups for
beta-endorphin (BE) shoulders. Massage took changes in OT, ACTH, NO,
place in a semiprivate and BE. Individuals receiving
room. massages showed a significant
Provider: trained mas- increase in OT between base-
seuse line and the second blood
Comparator(s) draw. A similar comparison in
Control: The team asked the control group showed a
participants to rest by decrease in OT that trended
sitting in chairs for 15 toward significance. OLS
minutes in the same regressions showed that mas-
rooms where partici- sage was associated with
pants in the massage higher OT compared to rest
group had received mas- and that massage accounted
sages. for 2.8% of the variation in
OT levels. A t-test demon-
strated that massage also
accounted for the significant
difference in the change in OT
between the two groups.
Women who received massage
did not release significantly
more OT than men; however,
women who rested did show a
change marginally higher in
magnitude than men. Massage
alone predicted25% of the
variation in OT change, and
massage and gender explained
30% of the variation in the
change.

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SYSTEMATIC REVIEW F. Kerr et al.

(Continued)
Citation Study aims Setting Study Type Population (N ¼ ) Intervention Outcomes Key findings

Mormann et al. To directly address Germany, Non-RCT People with epi- Live encounter with the Amygdala No significant differences in
(2015)129 the amygdala’s role Lab lepsy (14) researcher randomly activity response to gaze direction for
in processing eye changing gaze from the live encounter. Further,
gaze direct gaze to averted activity was less for the live
gaze to closed eyes over encounter than with the photo
a period of two minutes. images.
Provider: researcher
Comparator(s)
Images of faces with dif-
ferent gaze
Neu, Lauden- To examine coregu- USA, Clinical Correlational Mothers and their Mothers held their Cortisol (sali- Salivary cortisol levels of
slager & Robin- lation between studies preterm infants infants for 60 minutes in vary) mothers and infants were sig-
104
son (2009) mothers and pre- postconceptional the method that was nificantly closer at the end of
term infants in age of 33 to 36 usual. 11 used the Skin- a 60-minute holding session
hypothalamic-pitui- weeks. (20 dyads) to-skin method (Kanga- than they were before holding
tary-adrenocortical roo) and 9 used tradi- began, indicating coregulation
(HPA) system activ- tional horizontal in cortisol levels. The kanga-
ity, as indicated by holding. Cortisol levels roo method was not associ-
salivary cortisol were taken at the com- ated with greater maternal
levels, while mencement of holding infant cortisol coregulation.
mothers held their and at 60 minutes.
infants. Provider: mother
Noto, Kudo & To determine Japan, Lab Pre-test Post- Healthy female Standardized massage of Cortisol (sali- a-Amylase, cortisol, and chro-
Hirota whether salivary test nursing students the back for 10 minutes vary) a-Amylase mogranin A did not decrease
(2010)121 biomarkers are use- (25) with non-aromatic oil activity (sali-
ful objective indices Provider: not stated vary) Chrom-
for assessing the granin A
effects of back mas- (salivary)
sage on mental sta-
tus
Pinar & Afsar The objective of this Turkey, Clin- RCT Family caregivers Massage for 15 minutes State anxiety Anxiety scores decreased sig-
(2015)105 study was to evalu- ical of cancer patients per day for a week. Each (STIA) Cortisol nificantly in the massage
ate the effect of (44) massage session, consist- (serum) BP HR group. Plasma cortisol levels
back massage on ing of a combination of in the intervention group were
the anxiety state, effleurage (rhythmic, significantly decreased after
cortisol level, sys- gliding strokes), petris- massage. Both BP and HR,
tolic/diastolic blood sage (gentle kneading), which are a physiological indi-
pressure, pulse rate, friction (rhythmic press- cators, significantly decreased
and sleep quality in ing), and tapotement by massage in the intervention
family caregivers of (quick, striking move- group.
patients with cancer ments or beating),
started on the dorsal-
lumbar region, followed
by the back, scapulas,
shoulders, neck, and
scalp (from frontal area
to occipital area). Before
the massage, the care-
givers in the intervention
group rested in a chair
for 10 minutes in a
silence room.
Provider: massage
trained clinician Com-
parator(s)
The control group rested
quietly in a different
silence room
Pönkänen et al. To investigate Finland, Lab Non RCT University under- Static faces of an adult Event Related As hypothesized, the N170
(2011)133 whether a model’s graduates with female displaying a neu- Potential (ERP), and EPN were greater for
direct gaze enhances normal or cor- tral emotion and gazing N170 direct vs averted gaze and
ERP responses to rected-to-normal either straight forward closed eyes in the live condi-
faces and whether vision (20) (direct), gazing to the tion only.
this enhancement left or to the right
depends on the (averted), or having the
mode of stimulus eyes closed (closed).
presentation (live or Mode of delivery was a
picture). picture.
Provider: model
Comparator(s)
Mode of delivery was
live.

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(Continued)
Citation Study aims Setting Study Type Population (N ¼ ) Intervention Outcomes Key findings

Post-White To determine USA, Clinical RCT Children with Massage therapy (MT): Cortisol (sali- Changes in salivary cortisol
et al. (2009)106 whether 4 weekly cancer, 1 to 18 4 weekly sessions. Mas- vary) were not significantly different
sessions of massage, years of age, and sage included the back, between the MT and QT con-
compared with 4 1 parent or legs, arms, stomach/ ditions.
quiet-time control guardian. (25) chest, and face. After 4
conditions, would sessions participants
reduce anxiety, cor- were crossed over to
tisol, fatigue, nau- receive the alternative
sea, and pain in condition.
children with cancer Provider: trained mas-
undergoing chemo- seuse
therapy and would Comparator(s)
reduce anxiety, Quiet time (QT): chil-
fatigue, and mood dren and parents read,
disturbance in a rested, talked quietly, or
parent. watched a video.
Rapaport, To determine effects USA, Lab RCT Subjects were 45 minutes of Swedish Cortisol (sali- Swedish Massage Therapy
Schettler & Bre- of a single session medically healthy massage by a trained vary and caused a relatively large
see (2010)42 of Swedish massage and free of any therapist. Techniques plasma) Oxyto- decrease in AVP (as measured
on neuroendocrine current or past included effleurage, pet- cin (plasma) by effect size) and relatively
and immune func- Axis I psychopa- rissage, kneading, tapo- Arginine vaso- small, but consistent decreases
tion. It was hypoth- thology (53) tement, and thumb pressin (AVP) in salivary and serum cortisol
esized that Swedish friction. (plasma) Adre- levels. Massage Therapy did
Massage Therapy An identical protocol, nal corticotro- not increase OT nor decrease
would increase oxy- except that the therapist pin hormone ACTH, compared to the light
tocin (OT) levels, used only a light touch (ACTH) touch control condition.
which would lead to with the back of the (plasma)
a decrease in hypo- hand Provider: trained
thalamic-pituitary- masseuse
adrenal (HPA) activ-
ity and enhanced
immune function
Rapaport, To investigate the USA, Lab RCT Subjects were 45 minutes of Swedish Cortisol (sali- Twice-weekly massage
Schettler & Bre- effects of Swedish medically healthy massage by a trained vary and potentiates neuroendocrine
see (2012)116 massage versus a and free of any therapist. Techniques plasma) Oxyto- changes so that massage ther-
light touch interven- current or past included effleurage, pet- cin (plasma) apy might be mediated
tion on neuroendo- Axis I psychopa- rissage, kneading, tapo- Arginine vaso- through OT and AVP. The
crine and immune thology (45) tement, and thumb pressin (plasma) twice-a-week massage group
parameters. friction. Provider: Adrenal corti- demonstrated greater changes
trained masseuse Group cotropin hor- in OT, AVP, ACTH, and cor-
1 had the therapy 1X mone (plasma) tisol than the twice-a week
per week for 5 weeks. touch group, changes that
Group 2 had therapy 2X were sustained over a 3–4-day
per week for 5 weeks. period between treatments.
Comparator(s)
light touch with the back
of the hand. Group 3
had the therapy 1X per
week for 5 weeks.
Group 4 had therapy 2X
per week for 5 weeks.
Stringer, Swin- Massage both with UK, Clinical RCT Isolated haemato- Single session (20 min- Cortisol Reduction in stress hormone
dell & Dennis and without essen- logical oncology utes) of Aroma therapy (plasma) levels following single sessions
(2008)107 tial oils can be given patients (39) massage of light effleu- of massage in isolated patients
to isolated haema- rage on body part cho- undergoing high-dose chemo-
tology patients sen by patient. therapy.
safely; and the phys- Provider: massage
iological and psy- trained clinician
chological benefit Comparator(s)
demonstrated fol- (1) Single session (20
lowing massage in minutes) of Base oil mas-
ambulatory cancer sage of light effleurage
care is evident. on body part chosen by
patient (2) Rest for 20
minutes

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SYSTEMATIC REVIEW F. Kerr et al.

(Continued)
Citation Study aims Setting Study Type Population (N ¼ ) Intervention Outcomes Key findings

Taylor et al. To examine the USA, Clinical RCT Women who Usual Care (UC) plus Cortisol (uri- After adjusting for the
(2003)108 effects of adjunctive underwent an massage therapy: stan- nary) patients’ characteristics, no
postoperative mas- abdominal lapa- dardized 45-minute ses- significant differences were
sage and vibration rotomy for sions of gentle Swedish found between the three treat-
therapy on short- removal of sus- massage on the 3 conse- ment groups with regard to
term postsurgical pected cancerous cutive evenings after sur- 24-hour urine free cortisol
pain, negative affect, lesions (150) gery.
and physiologic Provider: trained mas-
stress reactivity seuse Comparator(s)
(1) UC plus vibration
therapy: 20-minute ses-
sions of inaudible vibra-
tion therapy
(physiotones) on the 3
consecutive evenings
after surgery, as well as
additional sessions as
desired. (2) Usual post-
operative care
Tsuji et al. The objective was Japan, Home Pre-test post- Children with 20 minutes prior to bed- Oxytocin (sali- The results indicated that ASD
(2015)109 to measure the test autism spectrum time, every day for 3 vary) children and their mothers
impact on Oxytocin disorder (ASD) months. Participants’ exhibited higher salivary con-
levels in autistic aged 8–12 years mothers were trained in centrations of OT during the
children when (7) massage by a massage repeated massage period for 3
mothers provided therapist.This involved months, compared to those
gentle touch mas- gentle and warm mas- during the non-massage (rest)
sage sage with weak pressure period for 4months.
for the child’s body.
Provider: mother
Comparator(s)
4 month period of non-
massage following cessa-
tion of intervention.
Ulmer-Yaniv The current study Israel, Lab Non-RCT Healthy young Parents were instructed Oxytocin (OT) OT significantly increased
et al. (2016)134 focused on human adults, with at to play with the infant (plasma) Beta during periods of parental and
adults during peri- least. 35 singles for approximately 10 endorphin (b- romantic bonding and was
ods of parental and who were not minutes ‘‘the way they End) (plasma) highest in new lovers. In con-
pair bond forma- involved in a play at home’’. Lovers Interlukin-6 trast, IL-6 and b-End were
tion. Plasma OT, b- romantic relation- were videotaped in a (IL-6) (plasma) highest in new parents and
End, and IL-6 were ship during the positive interaction for lowest in singles. Biomarkers
measured in new past six months approximately 10 min- became more tightly coupled
parents, new lovers, (17 men and 18 utes; they were asked to during periods of bond forma-
and singles and women), 50 indi- plan ‘‘the best day ever’’ tion and inter-correlation
behavioral syn- viduals (25 cou- to spend together. Inter- among hormones was highest
chrony during social ples) who began a actions were videotaped during romantic bonding.
interactions micro- romantic relation- and coded for time for Structural equation modeling
coded to understand ship within the gaze, affective facial indicated that the effects of
how functioning of past four months, expression, vocalization IL-6 and b-End on behavioral
these systems sup- and 115 new and touch. It is not clear synchrony were mediated by
port the expression mothers and what occurred with the their impact on OT, highlight-
of synchrony, a fathers (71 ’singles’ group. ing the integrative role of the
social experience mothers and 44 oxytocinergic system in sup-
critical for the fathers, not cou- porting human social affilia-
establishment of ples) of 4–6 tion. Findings suggest that
new bonds. month-old first- periods of bond formation are
born infants. accompanied by increased
(200) activity, as well as tighter
cross-talk among systems
underpinning affiliation,
reward, and stress manage-
ment.
Wandell et al. To study the effect Sweden, Clin- Quasi-RCT Patients with type 10 weeks of TM once/ Cortisol (uri- No significant difference in
(2010)110 of tactile massage ical 2 diabetes aged week (n ¼ 26) and follow nary) cortisol levels at follow-up for
(TM) or relaxation 35–75 years of up 3 months later. either group
exercises on meta- age, with metfor- Provider: trained mas-
bolic control min treatment. seuse
(HbA1c) in patients (53) Comparator(s)
with type 2 diabe- 10 weeks of relaxation
tes. The secondary using a compact disc
aim was to study once/week (n ¼ 27) and
stress parameters follow up 3 months
(cortisol and cate- later.
cholamines).

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WOLTERS KLUWER HEALTH, INC. ON BEHALF OF THE JOANNA BRIGGS INSTITUTE.
SYSTEMATIC REVIEW F. Kerr et al.

(Continued)
Citation Study aims Setting Study Type Population (N ¼ ) Intervention Outcomes Key findings

Wardell & To test a framework USA, Lab Pre-test post- Healthy adults Reiki touch (3 repeats). Cortisol (sali- There was no significant
Engebretson of relaxation or test (23) Treatments were given vary) change in cortisol levels before
(2001)117 stress reduction as a in the afternoon and and after treatment (15
mechanism of touch early evening to avoid dropped, 7 rose).
therapy through normal circadian rhythm
examination of changes in cortisol,
select physiological which are most dramatic
and biochemical before noon.
effects and the expe- Provider: trained mas-
rience of 30 minutes seuse
of Reiki (a form of
touch therapy).
Wikström, Gun- To investigate the Sweden, Lab Pre-test post- Volunteer sub- Swedish classic massage Oxytocin No overall difference in oxy-
narsson & Nor- effects of tactile sti- test jects; staff and was performed at 9am (plasma) Neu- tocin concentrations before
din (2003)118 muli (massage) on students of Lin- for 30 minutes (þ/–2), ropeptide Y and after massage was found
plasma oxytocin köping University using unscented vegeta- (NPY) either for men or for women.
and neuropeptide Y and their family ble oil. Massage was Focusing on the difference (II-
(NPY) members (21) administered to the I) between concentrations
back, including the pos- immediately before and after
terior neck and the massage session, a sex
shoulders, with the sub- difference was found for oxy-
ject in the prone posi- tocin as well as NPY.
tion. No verbal
communication occurred
during the massage.
Provider: trained mas-
seuse
Wu et al. The effects of aro- South Korea, RCT Females whose Aromatherapy massage EEG activity Significant enhancement of
(2014)124 matherapy massage Lab children were for 40 minutes twice per Plasma brain- alpha and reduction of delta
on multiple neurobi- diagnosed with week for 4 weeks (eight derived neuro- after a 15-minute aromather-
ological indices such attention deficit times in total). Included trophic factor apy massage. No significant
as quantitative psy- hyperactivity dis- bath, then 20 ml of (BDNF) Corti- differences in basal EEG pat-
chological assess- order (25) Jojoba oil containing sol (salivary terns. Salivary cortisol levels
ments, electroen- mixed essential oils (lav- and plasma) were significantly decreased
cephalogram (EEG) ender, geranium) with when they were measured at
power spectrum pat- effleurage, friction, pet- approximately 15 minutes
tern, salivary corti- rissage and vibration after the one-time aromather-
sol and plasma treatment. apy massage treatment, com-
brain-derived neuro- Provider: trained mas- pared to the time point just
trophic factor seuse before treatment. Basal corti-
(BDNF) levels Comparator(s) sol levels in plasma were not
Control group: no treat- substantially changed after the
ment 4-week program in both the
control and therapy groups.
There were no significant dif-
ferences in basal cortisol after
4 weeks.

BP, blood pressure; CCU, coronary care unit; CT, cortisol; GA, gestational age; GHT, gentle human touch; KC, kangaroo care; MSFP, Modified Still Face Procedure; NE,
norepinephrine; NK cells, natural killer cells; OT, oxytocin; PIPP, Premature Infant Pain Profile; QTN, Qi no touching; QTT, Qi touching; RCT, Randomized controlled trial;
SSC, skin-to-skin contact; TM, tactile massage; TTM, traditional Thai massage; WC, warm contact.

JBI Database of Systematic Reviews and Implementation Reports COPYRIGHT ß 2018 THE AUTHORS. PUBLISHED BY 247
WOLTERS KLUWER HEALTH, INC. ON BEHALF OF THE JOANNA BRIGGS INSTITUTE.