REVIEW

published: 03 May 2019

doi: 10.3389/fphys.2019.00536

Eccentric Muscle Contractions:

Risks and Benefits
Stéphanie Hody 1* , Jean-Louis Croisier 1 , Thierry Bury 1 , Bernard Rogister 2,3,4 and
Pierre Leprince 2,4
1
Department of Motricity Sciences, University of Liège, Liege, Belgium, 2 GIGA-Neurosciences, University of Liège, Liege,
Belgium, 3 Department of Neurology, The University Hospital Center, University of Liège, Liege, Belgium, 4 GIGA – Laboratory
of Nervous System Disorders and Therapy, University of Liège, Liege, Belgium

Eccentric contractions, characterized by the lengthening of the muscle-tendon complex,

present several unique features compared with other types of contractions, which may
lead to unique adaptations. Due to its specific physiological and mechanical properties,
there is an increasing interest in employing eccentric muscle work for rehabilitation and
clinical purposes. However, unaccustomed eccentric exercise is known to cause muscle
damage and delayed pain, commonly defined as “Delayed-Onset Muscular Soreness”
(DOMS). To date, the most useful preventive strategy to avoid these adverse effects
consists of repeating sessions involving submaximal eccentric contractions whose
intensity is progressively increased over the training. Despite an increased number
Edited by: of investigations focusing on the eccentric contraction, a significant gap still remains
Dario Coletti,
Sapienza University of Rome, Italy in our understanding of the cellular and molecular mechanisms underlying the initial
Reviewed by: damage response and subsequent adaptations to eccentric exercise. Yet, unraveling
Damien Vitiello, the molecular basis of exercise-related muscle damage and soreness might help
Université Paris Descartes, France
uncover the mechanistic basis of pathological conditions as myalgia or neuromuscular
Nissrine Daou,
Pierre and Marie Curie University, diseases. In addition, a better insight into the mechanisms governing eccentric training
France adaptations should provide invaluable information for designing therapeutic interventions
*Correspondence: and identifying potential therapeutic targets.
Stéphanie Hody
[email protected] Keywords: skeletal muscle, eccentric contraction, exercise-induced muscle damage (EIMD), delayed-onset
muscle soreness (DOMS), eccentric muscle training
Specialty section:
This article was submitted to
Striated Muscle Physiology,
a section of the journal
INTRODUCTION
Frontiers in Physiology
An eccentric (lengthening) muscle contraction occurs when a force applied to the muscle exceeds
Received: 10 December 2018
the momentary force produced by the muscle itself, resulting in the forced lengthening of the
Accepted: 15 April 2019
muscle-tendon system while contracting (Lindstedt et al., 2001). During this process, the muscle
Published: 03 May 2019
absorbs energy developed by an external load, explaining why eccentric action is also called
Citation:
“negative work” as opposed to concentric (shortening) contraction or “positive work” (Abbott et al.,
Hody S, Croisier J-L, Bury T,
Rogister B and Leprince P (2019)
1952). Although not always obvious, eccentric muscle contractions are an integral part of most
Eccentric Muscle Contractions: Risks movements during daily or sport activities. Skeletal muscles contract eccentrically to support the
and Benefits. Front. Physiol. 10:536. weight of the body against gravity and to absorb shock or to store elastic recoil energy in preparation
doi: 10.3389/fphys.2019.00536 for concentric (or accelerating) contractions (LaStayo et al., 2003b). The slowing-down role of such

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Hody et al. Eccentric Exercise

contractions is classically illustrated by downhill running or eccentric tasks. Robust evidence support its wide prescription
walking down the stairs during which the eccentric work of the in the sport rehabilitation field, notably in the treatment
knee extensor muscles is accentuated (Gault and Willems, 2013). of tendinopathies (Croisier et al., 2007; Kaux et al., 2013).
Compared to concentric or isometric (constant length) In addition, implementing eccentric exercise in athletes showed
contractions, eccentric muscle actions possess several unique its effectiveness to prevent sport injuries such as hamstring strain
features that may be responsible for unique adaptations (Guilhem (Croisier et al., 2002). While research has mainly focused on
et al., 2010; Duchateau and Baudry, 2014). Greater forces the functional outcomes following eccentric resistance training
are generated during eccentric contraction compared to other using high-loads, the potential of low/moderate load regimes
contraction types for a given angular velocity (Hortobagyi and received much attention over the last decade (LaStayo et al.,
Katch, 1990). In addition, eccentric contractions require less 2014; Hoppeler, 2016). With the increasing consideration of
motor unit activation and consume less oxygen and energy the physical activity in numerous medical fields over the last
for a given muscle force than concentric contractions (Abbott decades, a novel training modality based on low to moderate load
et al., 1952). Indeed, the metabolic cost required for eccentric ECC exercise has emerged. This modality, referred as RENEW
exercise is approximately fourfold lower than for the same (Resistance Exercise via Eccentric Work) by LaStayo et al. (2014),
exercise performed concentrically. Reduced cardiorespiratory appears to result in similar gains in muscle strength and volume
and hemodynamic responses have been reported following as traditional strength training. Since eccentric modality provides
eccentric exercise when compared to concentric exercise at a strong mechanical stress at a lower metabolic cost (Lastayo et al.,
the same absolute workload (Overend et al., 2000; Meyer 1999), it appears particularly suitable for training individuals with
et al., 2003). While many questions remains unanswered, medical conditions associated to muscle wasting and reduction
it is well accepted that neural strategies controlling eccentric in muscle strength, mobility and aerobic capacity (Hoppeler,
contractions considerably differ from concentric or isometric 2016). Eccentric training is increasingly proposed to patients
contractions (Duchateau and Baudry, 2014). Differences are with cardiorespiratory problems, sarcopenia of old age, cachexia,
detected on the level of the contracting muscle as well as diabetes type 2, neurological and musculoskeletal diseases (Julian
on the cortical level. Most studies indicate a reduced central et al., 2018). Along with the positive effects on the muscle
activation (evidenced by a lower EMG amplitude) during function, aerobic eccentric exercise induces specific effects on
maximal eccentric contractions than maximal concentric or muscle energetic metabolism, insulin resistance and blood lipid
isometric contractions. This has implications on eccentric profile, reducing disease risks. It is thus recognized as a promising
coordination: fine motor control in eccentrically biased actions lifestyle factor to combat obesity and dyslipidemias (Paschalis
appears more difficult as fewer motor-units are required for the et al., 2010; Julian et al., 2018, 2019).
same work (Hoppeler, 2016). The twitch interpolation technique However, despite the above-mentioned advantages, the use
also revealed a greater voluntary deficit in eccentric compared of eccentric exercise in clinical conditions has been frequently
to concentric contractions, such that untrained individuals are the object of contrasting opinions, because of its potential
usually unable to fully activate their muscles during maximal undesirable associated effects. Indeed, eccentric exercise induces
eccentric muscle contractions. Further characteristics of eccentric greater muscle damage and negative functional consequences in
contraction are a greater cortical excitability but a lower motor an healthy naïve muscle than other types of exercise (Friden and
units discharge. Collectively, the mechanisms underpinning the Lieber, 1992). Indeed, the combination of high force and reduced
unique features of eccentric contraction are not well understood recruitment of fiber number during eccentric contractions
(Hoppeler and Herzog, 2014). causes a high mechanical stress on the involved structures that
Due to its specific physiological and mechanical properties, may lead to focal microlesions of the muscle fibers (Lieber
the eccentric contraction has gained a growing interest in several and Friden, 1999). Numerous histological studies described
fields. Besides its interest in sport training or in physical medicine widespread Z-line streaming with myofibrillar disruption and
and rehabilitation (Croisier et al., 2002; Kjaer and Heinemeier, necrosis following intense and/or unaccustomed eccentric
2014; Vogt and Hoppeler, 2014), evidence is accumulating exercise (Friden and Lieber, 1998; Crameri et al., 2007; Lauritzen
regarding the benefits of eccentric exercise in special populations et al., 2009). The sarcomeric disorganization has been associated
of aged individuals or patients with chronic health diseases with disruptions to the sarcolemma and the extracellular
such as neuromuscular pathologies (Roig et al., 2008; Gault and matrix, swelling of mitochondria, dilation of the transverse
Willems, 2013; Isner-Horobeti et al., 2013; Hyldahl and Hubal, tubule system and fragmentation of the sarcoplasmic reticulum
2014). Indeed, the two main defining properties of eccentric (Takekura et al., 2001; Crameri et al., 2004). Sarcolemmal
contraction “highest forces and lower energy requirement” makes disruption may be highlighted by the appearance of sarcoplasmic
this contraction regime a judicious alternative to conventional proteins into the blood (as creatine kinase, CK and myoglobin,
muscle training. To date, it is well accepted that the benefits Mb) or by the cytoplasmic accumulation of proteins that
of eccentric exercise transcend improved muscle function, are normally not present in muscle fibers (as albumin and
as this mode of training has been shown to induce a number immunoglobulins) (McNeil and Khakee, 1992; Clarkson and
of favorable repercussions on neural drive or health-related Hubal, 2002). Vital dye such as Evans blue is also used in
factors (Paschalis et al., 2010, 2013). For many years, eccentric rodents to demonstrate increased sarcolemmal permeability
regime has been largely used in sport training to improve (Hamer et al., 2002). Damage to extracellular matrix and
maximal muscular strength, power as well as coordination during connective tissue components also occur following a novel

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Hody et al. Eccentric Exercise

eccentric exercise (Brown et al., 1997; Crameri et al., 2007). Barnett, 2006; Bloomer, 2007; Howatson and van Someren,
Morphological abnormalities observed immediately after exercise 2008). Despite the large number of clinical trials, there are
gradually extent to a larger number of muscle fibers and appear very few evidence-based guidelines for the application of these
exacerbated 2–3 days post-exercise (Friden et al., 1983a). These interventions. The inconsistencies in the dose and frequency
observations have led authors to define primary and secondary of the investigated interventions may account for the lack
damage phases (Morgan and Allen, 1999). Both human and of consensus regarding their efficacy. Conversely, there is
animal studies supported that Type II (in particular IIb) muscle unequivocal evidence that a first bout of eccentric exercise confers
fibers are more damaged after eccentric exercise than Type I fibers protection against EIMD following a subsequent bout of the
(Friden et al., 1983b; Jones et al., 1986; Lieber and Friden, 1988). similar exercise. This muscle adaptation process, commonly
Several hypotheses could explain the higher susceptibility of Type called “the repeated-bout effect” (RBE), is characterized by
II fibers to exercise-induced muscle damage (EIMD). Among reduced increases in muscular proteins in the blood, attenuated
these are differences in their structural composition (Z-line, fiber DOMS, less muscle swelling, reduced abnormality in echo
type specific protein isoforms such as titin), a reduced oxidative intensity of B-mode ultrasound and/or magnetic resonance
capacity, a lower ability to regulate calcium homeostasis or a images and faster recovery of muscle strength and range of
selective recruitment of fast-twitch muscle fibers during eccentric motion following the repeated bout (McHugh, 2003; Nosaka
contraction (Lieber and Friden, 1999; McHugh et al., 1999a; and Aoki, 2011). Although a significant protective effect occurs
Byrne et al., 2004). after a single eccentric bout (Clarkson et al., 1992; Nosaka and
The EIMD manifests itself by a range of clinical symptoms Clarkson, 1995), the adaptive process appears more complete
including delayed-onset muscle soreness (DOMS), stiffness, after several sessions (Croisier et al., 1999; Hody et al., 2011).
swelling and various functional deficits such as a loss in The RBE seems to imply long-lasting adaptation since it
force generating capacity or decreased proprioceptive function persists for several weeks and even up to 6 months but
(Clarkson, 1992). To avoid the invasive nature of muscle the magnitude of the protection decreases over time (Nosaka
biopsies, these clinical manifestations as well as the plasma CK et al., 2001, 2005). It is interesting to note that the magnitude
activity are frequently used to indirectly assess the presence of the protective effect is not necessarily dependent on the
of muscle damage (Warren et al., 1999; Clarkson and Hubal, severity of the initial muscle damage. It has been demonstrated
2002). The magnitude of changes in EIMD indirect markers that repeating bouts of “non-damaging” eccentric exercise can
(in particular, the plasma CK activity) shows a marked inter- provide strong protective adaptations against subsequent bouts
individual variability even when subjects are submitted to of maximal eccentric exercise (Chen et al., 2013). Therefore, to
standardized eccentric protocols (Clarkson et al., 1992; Nosaka date, performing repeated sessions with submaximal eccentric
and Clarkson, 1996; Hody et al., 2013c). Multiple factors as contractions appears to be the most efficient strategy to induce
muscle architecture, muscle typology, individual fitness, age, sex, eccentric training-induced adaptations that would prevent
and genetic variability may contribute to the wide inter-subject further EIMD and DOMS. The demonstration that eccentric
variability in the response to eccentric exercise (Vincent and actions can be performed without damage and soreness allowed
Vincent, 1997; Clarkson and Hubal, 2002; Yamin et al., 2007; considering the potential of eccentric trainings in medical
Hody et al., 2009; Hyldahl and Hubal, 2014). Even if DOMS conditions. Studies conducted first with healthy subjects and
and associated clinical symptoms spontaneously disappear after then, with patient populations, have supported the application
few days, these negative consequences can delay or disturb of eccentric trainings as a safe, feasible and efficient strategy for
rehabilitation and/or training programs. Exercise is necessary to rehabilitation purposes (LaStayo et al., 2000; Hoppeler, 2016).
maintain a good health and to prevent physical inactivity-related Numerous studies have attempted to elucidate the mechanisms
diseases, but unpleasant sensations resulting from unaccustomed underlying the RBE, but this feature of the skeletal muscle is
exercise can discourage people to continue physical activity. not fully understood (McHugh et al., 1999a; McHugh, 2003;
Moreover, due to the mechanical fragility, the risk of further Nosaka and Aoki, 2011).
injuries (e.g., muscle tears or ligament rupture) increases if Despite considerable amount of available data at the clinical
intense physical activities are performed during a DOMS episode and histological levels, a significant gap still remains in the
or the following days (Nicol et al., 2006). It is worth noting that understanding of the mechanisms that mediate morphological,
muscle soreness disappears before the full recovery of muscle cellular, and molecular responses to muscle damaging eccentric
function, further elevating the injury incidence (Strojnik et al., exercise (Hoppeler and Herzog, 2014). In addition, the
2001). Although exceptional, extreme CK and Mb elevations molecular events underlying the specific eccentric training
associated with EIMD could be severe enough to provoke a muscle adaptations are not fully understood (McHugh, 2003;
kidney tubulopathy (Sayers et al., 1999). Nosaka and Aoki, 2011). This review begins by describing the
Given the risks and drawbacks related to the occurrence potential mechanisms leading to muscle damage and soreness
of EIMD described above, the development of strategies to following unaccustomed eccentric exercise. Then, are discussed
prevent or reduce the intensity of its clinical manifestations the current knowledge of the eccentric training-induced
has become a primary goal of many studies. The most adaptations including the main hypotheses of the protective effect
commonly used approaches include stretching, cryotherapy, against EIMD. Finally, the multiple applications of eccentric
electric or manual therapies, whole-body vibration or nutritional training, justifying the need of an improved understanding of its
and pharmacological interventions (Cheung et al., 2003; underlying molecular and cellular mechanisms, are exposed.

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Hody et al. Eccentric Exercise

UNACCUSTOMED ECCENTRIC which in turn, will increase calcium entry. Elevated calcium
EXERCISE concentrations in skeletal muscle mitochondria, which can
alter mitochondrial respiratory function, also occur following
unaccustomed eccentric exercise (Rattray et al., 2011, 2013).
Mechanisms of Exercise-Induced
This calcium overload may be associated with the opening
Muscle Damage of the mitochondrial permeability transition pore (mPTP)
It is generally accepted that the damage process is initiated leading to the activation of cell death signaling or with the
due to a lack of homogeneity in sarcomeres stretching increased calpain proteolytic activity which is capable of targeting
(asymmetric lengthening). This theory initially proposed by proteins resulting in mitochondrial dysfunction. Furthermore,
Morgan (1990) suggests that during eccentric contractions, the the increased calpains activity can promote neutrophils and
weakest sarcomeres or even half-sarcomeres will absorb most macrophages activation, leading to ROS production (Powers and
of the length change (Morgan, 1990). These may be stretched Jackson, 2008). Besides the clinical symptoms associated with
beyond the point of myofilament overlap resulting in disrupted EIMD (such as DOMS and decline in muscle strength), EIMD
or “popped” sarcomeres. In line with this proposal, several have been reported to induce metabolic consequences at the acute
studies have clearly shown that the length of the muscle during phase: decreased glucose uptake and insulin sensitivity, impaired
eccentric contraction is a critical factor in determining the extent glycogen synthesis, elevated metabolic rate and a shift toward
of damage (Talbot and Morgan, 1998). Eccentric contractions non-oxidative metabolism (Tee et al., 2007).
performed at longer muscle length results in greater symptoms
of damage than similar contractions at shorter muscle length
(Lieber and Friden, 1993). Inflammatory and Immune Responses
The initial mechanical damage would trigger a cascade of to Eccentric Exercise
events leading to more severe secondary damage (Figure 1). While the development of an inflammatory reaction after
Loss of calcium homeostasis, possible inflammatory reaction eccentric exercise has been debated (Yu et al., 2002; Malm and Yu,
and reactive oxygen species (ROS) production are thought to 2012), many studies have now provided clear evidence of systemic
contribute to the secondary damage phase. The disturbances in and local inflammatory responses in both rodents and humans
Ca2+ homeostasis observed following unaccustomed eccentric following various types of eccentric exercise (Peake J. et al., 2005;
exercise may be the consequence of membrane damage Paulsen et al., 2012). However, in contrast to extensive works
(Friden and Lieber, 2001) or opening of stretch-activated describing the histological and clinical signs associated to EIMD,
channels (Overgaard et al., 2002). Abnormal increase in the mechanisms underlying the inflammation-immune responses
calcium concentration inside muscle cells is responsible for and the subsequent regenerative events are less well understood
the activation of muscle proteases, named calpains. Since these (Peake J. et al., 2005; Paulsen et al., 2012). The inflammation
proteases cleave important structural proteins in charge of processes following damaging exercise was initially considered as
myofibril integrity (as desmin and alpha-actinin), they have been a detrimental event due to its association with muscle damage,
suggested to contribute to EIMD. The degradation of proteins soreness and delayed recovery but it is now well accepted that
released from myofibrillar structures by the calpains could the inflammatory stages are crucial for functional recovery of the
be enhanced by other proteolytic pathways as the ubiquitin– muscle to EIMD. The inflammation would ensure the removal of
proteasome system (Raastad et al., 2010). Activation of calpains tissue debris from the injured area and promote muscle repair
may also result in the destruction of membrane constituents, by activating muscle cells. Over the last decade, more studies

FIGURE 1 | Summary of the main specific features of eccentric contraction, its multi-target beneficial effects and potential risks associated with unaccustomed
and/or maximal eccentric exercise.

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Hody et al. Eccentric Exercise

have focused on the implication of multiple immune cell types (Paulsen et al., 2012). The latter can also promote general protein
interacting with the muscle and emphasized the undeniable role synthesis within muscle fibers. The replacement of macrophages
of satellite cells for muscle regeneration following one bout of M1 to anti-inflammatory M2 macrophages is a key stage for
eccentric exercise (Crameri et al., 2004; Paulsen et al., 2012). the transition from proinflammatory to anti-inflammatory
Early accumulation of leukocytes, primarily neutrophils, has stages. This process is regulated by different signals including
been observed in micro-blood vessels of the damaged muscle, the phagocytosis of cell debris, IL10 and AMP-activated protein
as well as in the perimysium, immediately after exercise. kinase (Chazaud, 2016). While a large body of research has
In case of moderate to severe EIMD, histological studies primarily focused on neutrophils and macrophages, other
have consistently shown that neutrophils infiltrate into the cell types interact with the muscle and are important in the
muscle and accumulate in the damaged area from 1 and inflammation and muscle regeneration processes. These include
24 h after eccentric exercise (Paulsen et al., 2010). It is notably mast cells, T lymphocytes, eosinophils, fibro-adipogenic
likely that secretion and/or passive release of chemoattractant progenitors, and pericytes (Paulsen et al., 2012).
proteins due to modifications to membrane permeability are The inflammation and immune responses are mediated by
involved in the recruitment of circulating inflammatory cells. various growth factors and the actions of exercise-responsive
They initiate the pro-inflammatory stage through phagocytosis cytokines (i.e., IL-6, CCL2, and interferon-γ), pro-inflammatory
and by releasing proteolytic enzymes (such as elastase or cytokines (TNF-α and IL-1β) and the anti-inflammatory cytokine
myeloperoxidase) and reactive species. At later time points, IL-10. Collectively, all these cytokines appear to activate myoblast
when neutrophils are cleared from muscle, pro-inflammatory proliferation and some of them are involved in myoblast
macrophages start to accumulate. This type of macrophages, differentiation (Peake J. et al., 2005). Interestingly, the satellite
referred as M1, contribute to the phagocytosis of the damaged cells activity is differentially affected by the contraction mode
tissue by secreting pro-inflammatory cytokines (e.g., TNF-α, in human muscle following exercise of the same work load.
IL-6, and IL-1β) and secretory leukocyte protease inhibitor. Resistance eccentric, but not concentric, exercise has been
Tissue-resident monocytes may also become activated after shown to elicit the proliferation of satellite cells immediately
exercise, in addition to the leukocytes originating from the after exercise, suggesting that EIMD is the main stimulus for
blood circulation. Neutrophils and M1 macrophages interact activating the satellite cells pool (Hyldahl and Hubal, 2014;
with each other to regulate the proinflammatory response Hyldahl et al., 2014).
of muscle damage. Their influx inside injured myofibers The precise source of production for cytokines found in the
appears to be dependent on the magnitude of EIMD and circulation during and after exercise is not well established.
may lead to an exacerbation of the initial cellular alterations. Indeed, the cytokines can be produced not only by leucocytes, but
Conversely, M2 macrophages that appear later generally produce also by myofibers and peri-tendinous tissue (Paulsen et al., 2010).
anti-inflammatory cytokines and signaling molecules involved The term “myokines” has been introduced to refer to muscle
in the muscle recovery and regeneration. Large variations derived-cytokines and chemokines. Myokines are secreted by
across healthy individuals are observed, some presenting the skeletal muscle in order to communicate with non-muscle
substantial leukocyte accumulation whereas others displayed tissues and act as auto-, para- and endocrine mediators. These
very little leukocytes invasion. Furthermore, the magnitude of might be molecular mediators which link muscle exercise and
the inflammation response appears to be dependent on the the whole body physiology (Schnyder and Handschin, 2015).
initial perturbations induced by the exercise. It is assumed While research to date has focused primarily on the biological
that minor perturbations result in a cell-signaling-mediated functions of the myokines in regulating metabolism, much less
adaptive response, whereas intense eccentric actions seem to attention has been made regarding their role in inflammatory
generate a more severe response leading to secondary damage and adaptation to EIMD (Paulsen et al., 2010). Nevertheless,
to myofibers and increased risk of necrosis. While significant studies investigating the cytokine responses to eccentric exercise
necrosis is observed after electrically stimulated contractions, demonstrated increased activity of some cytokines such as MCP-1
segmental myofiber necrosis may occur without affecting the and IL-10 after eccentric but not concentric exercise (Hyldahl and
whole myofiber, even in severe cases of EIMD. Interestingly, Hubal, 2014). The anti-inflammatory cytokine IL-10 may attract
the degree of leucocyte accumulation seems to be related to the T lymphocytes, which activate muscle cell proliferation and
changes in force-generating capacity of the muscle (Paulsen et al., muscle regeneration. Systemic increase of IL-8 and upregulation
2010). Therefore, measuring the decline of muscular strength in intramuscular IL-8 mRNA expression and plasma levels after
following exercise, which is recognized as the best indirect marker downhill running and eccentric actions of the quadriceps has also
of EIMD, may inform on the status of the muscle. In contrast, been reported (Hubal et al., 2008; Buford et al., 2009). IL-8 plasma
the level of leukocyte invasion into injured myofibers is not levels are also increased after eccentric muscle contractions,
necessarily related to DOMS. but unchanged following concentric exercise. IL-8 is known to
The muscle inflammatory response appears to intimately attract primary neutrophils but this chemokine may also promote
coregulate with muscle regeneration. Indeed, additionally to their neovascularization of muscle tissue through its association with
immune functions, macrophages also participate to myogenesis CXCR2 (Schnyder and Handschin, 2015). Some studies also
and contribute to the extracellular matrix remodeling. showed an increase in plasma concentration of IL-1ra and
M1 macrophages stimulate satellite cells proliferation whereas G-CSF (granulocyte-colony stimulating factor) in the hours after
M2 macrophages interact with differentiating satellite cells eccentric exercise (Peake J. et al., 2005; Peake J.M. et al., 2005).

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Hody et al. Eccentric Exercise

A large body of science has focused on IL-6. This myokine, as important players in the development of DOMS following
considered as one “exercise factor,” is regulated by exercise and eccentric contractions (Figure 1). Using a rodent model, they
acts both locally within the muscle and on distal organs in an demonstrated that a bradykinin-like substance released from
endocrine-like fashion (Catoire and Kersten, 2015). IL-6 has the muscle during eccentric exercise triggers the process of
initially been characterized as a prototypical pro-inflammatory muscular mechanical hyperalgesia by upregulating NGF through
cytokine by contributing to neutrophil mobilization and B2 receptors in exercised muscle of rats. In humans, NGF has
activation and promoting impaired peripheral insulin resistance. been shown to be involved in the generation and potentiation
In contrast, anti-inflammatory properties of IL-6 have been of pain following eccentric exercise (Nie et al., 2009). Another
proposed later. Indeed, its exercise-induced systemic increase pathway proposed to be involved in the development of
generates the elevation of plasma level of several anti- DOMS is the activation of the COX-2-glial cell line-derived
inflammatory cytokines (IL-1ra and IL-10) and inhibits the neurotrophic factor (GDNF) (Murase et al., 2013; Mizumura
production of the pro-inflammatory cytokine TNF-α (Pedersen and Taguchi, 2016). Similarly to NGF pathway, this agent likely
and Febbraio, 2008; Pedersen, 2012). Various cell types secrete generates muscle mechanical hyperalgesia directly by stimulating
IL-6, including the skeletal muscle fibers during and after muscle nociceptors, or by binding to extracellular receptors.
exercise. Alongside the systemic increase, IL-6 mRNA levels are While myofibers micro-damage were believed to be necessary
augmented in contracting muscle fibers. IL-6 is considered as an to initiate inflammation and DOMS, some studies reported
energy sensor of the muscle (Pedersen, 2012) since its secretion mechanical hyperalgesia after eccentric exercises without any
from the exercising muscles increases glucose uptake and fatty signs of muscle damage. This supports the crucial roles of
acid oxidation locally and improves insulin secretion, which NGF and GDNF in DOMS and suggests that the mechanical
further increases glucose uptake into muscle fibers. Hepatic hyperalgesia development may be associated with inflammation
glucose delivery and fatty acid release from adipose tissue are also in the extracellular matrix (Peake J. M. et al., 2017). NGF
stimulated supporting the maintenance of metabolic homeostasis and GDNF are also known to play a role in pathological pain
during exercise (Febbraio and Pedersen, 2002). Muscle derived conditions and are increasingly recognized as active players in the
IL-6 was first thought to be related to injury but “non-damaging whole pain process and upregulated in ischemic skeletal muscle
exercise” has been shown to lead to substantial IL-6 increase (Turrini et al., 2002). NGF is increasingly regarded as an active
(Croisier et al., 1999). Nevertheless, IL-6 contributes with TNF-α player in the whole pain process (McKelvey et al., 2013). Thus,
and MCP-1 to muscle regeneration after EIMD by stimulating advances in the understanding of the mechanisms and cellular
the proliferation and differentiation of myoblasts (Schnyder and origins of muscle soreness could lead to development of effective
Handschin, 2015). Moreover, the transforming growth factor- interventions for not only exercise-related muscle soreness, but
beta is another cytokine involved in muscle recovery and also common myalgia.
repair after muscle damage that regulates extracellular matrix
remodeling and promotes fibrosis (Kim and Lee, 2017).
ECCENTRIC TRAINING-INDUCED
Delayed-Onset Muscle Soreness ADAPTATIONS
Delayed-onset muscle soreness (DOMS) refers to unpleasant,
dull, aching pain, usually felt during palpation, contraction Molecular Aspects
or stretching of the affected muscle. Such muscle soreness The distinct features of the eccentric contraction compared
typically appears 12–24 h after unaccustomed eccentric exercise, to other contraction modes are the source of specific training
peaks at between 24 and 72 h before progressively subsiding adaptations. A significant body of evidence suggests that
and disappearing within 5–7 days post-exercise. Interestingly, compared to concentric contractions, chronically performed
DOMS intensity is poorly correlated with other EIMD indirect eccentric contractions promote greater gains in strength, muscle
markers and seems thus not to reflect the magnitude of muscle mass and neural adaptations (Reeves et al., 2009; Roig et al.,
damage (Nosaka et al., 2002). Although DOMS is an extremely 2009). The mechanisms responsible for these adaptations are
common symptom, why DOMS occurs with a delay, and why underlined by modifications in gene expression. Indeed the
eccentric contraction but not shortening contraction induces process of exercise-induced adaptations in skeletal muscle
DOMS is not clearly understood. Several hypotheses have been involves multiple signaling mechanisms initiating transcription
put forward to explain the mechanism of DOMS. These include of specific genes that enable subsequent translation into a series
lactic acid release, spasm, connective tissue damage, muscle of new proteins (Coffey and Hawley, 2007). Several studies have
damage, inflammation and oxidative stress (Hyldahl and Hubal, reported that eccentric and concentric actions activate distinct
2014). For many years, the most widely supported hypothesis was muscular molecular pathways in humans (Kostek et al., 2007)
that the biochemical, thermal and mechanical changes associated and in rats (Chen et al., 2002). It has been shown that eccentric
with the inflammatory response sensitize small diameter muscles exercise triggers a progressive activation of genes responsible
afferents (types III and IV) that may then be at the origin for cellular growth and development, involved in muscular cell
of the sensation of muscle soreness (Friden and Lieber, 1992). hypertrophy processes. The expression levels of these genes
It was only in 2010 that Murase and coworkers provided new are more stimulated by eccentric actions than by isometric
insights into the molecular mechanisms of DOMS generation. or concentric actions (Chen et al., 2002; Barash et al., 2004;
They highlighted bradykinin and nerve growth factor (NGF) Kostek et al., 2007), presumably due to the unique mechanical

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Hody et al. Eccentric Exercise

FIGURE 2 | Schematic representation of the potential mechanisms associated with eccentric exercise-induced muscle damage and involved in the development of
DOMS. BD, bradykinin; CK, creatine kinase; DOMS, delayed-onset muscle soreness; E–C, excitation–contraction; GDNF, glial cell line-derived neurotrophic factor;
IL, interleukin; NGF, nerve growth factor; ROS/RNS, reactive oxygen and nitrogen species; TNF, tumor necrosis factor.

stress placed on the eccentrically contracted muscles. For produced and energy cost, it could provide different stimuli
example, in skeletal muscle, the effect of eccentric training was leading to distinct muscular and functional adaptations
greater than concentric training for liver-type insulin-like growth (Figure 2) (Franchi et al., 2017a). A significant body of evidence
factor I and mechano-growth factor (positive regulators of have suggested the superiority of eccentric resistance training in
muscle growth) (Barash et al., 2004). Such modifications in gene terms of muscular hypertrophy over concentric or conventional
expression profiles are thought to be regulated by mechanical strength trainings (Julian et al., 2018). Some studies also reported
signaling pathways involving proteins that are sensitive to the earlier increments in muscle mass with eccentric-based resistance
mechanical status of muscle cell (i.e., Microtubules-Associated training when compared with concentric training. However, the
Proteins or MAP proteins) (Hentzen et al., 2006). Transcriptome findings appear extremely variable to clearly confirm greater
analyses in eccentric-exercised muscles also revealed substantial gains in muscle mass following eccentric modalities (Julian
transcriptional activity related to the presence of leukocytes, et al., 2018). Indeed, in their review, Franchi et al. (2014) draw
immune-related signaling and adaptive remodeling of the the conclusion that the changes in muscle size are similar
intramuscular extracellular matrix until 96 h after exercise between eccentric and concentric training when matched for
(Neubauer et al., 2014). In comparison to concentric or isometric load or work. A systematic review and meta-analysis about the
contractions, eccentric contractions appear to upregulate muscle contribution of the different muscle actions to muscle growth
cell activity and anabolic signaling pathway to a greater extent showed a greater muscle mass gain with eccentric contractions
(Douglas et al., 2017). but the results did not reach significance (Schoenfeld et al., 2017).
Nevertheless, taking into account the energy demand to produce
Specific Muscle Adaptations to similar force or work, eccentric exercise may be considered as
Chronic Eccentric Exercise more efficient (Julian et al., 2018). Interestingly, contraction type
Because the eccentric contraction differs from other contraction tends to induce a region-specific hypertrophy. Greater increase
types notably in terms of force generation, maximum force in distal muscle size has been observed following eccentric

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Hody et al. Eccentric Exercise

training, while concentric training favors median-muscle mainly by recruiting a greater number of slow-twitch fibers
hypertrophy (Franchi et al., 2014). In addition, the hypertrophic (Warren et al., 2000; Chen, 2003; Starbuck and Eston, 2012). Such
responses to eccentric versus concentric contractions might be mechanisms would allow a better distribution of the workload
obtained by different structural adaptations mediated by distinct over a greater number of active muscle fibers in repeated bouts
myogenic and molecular responses. While both training regimes (Nosaka and Clarkson, 1995). The fast-setting adaptations but
appeared to increase muscle fascicle length and pennation also the existence of contralateral protective effect (Howatson
angle (Blazevich et al., 2007), conventional strength training and van Someren, 2007; Starbuck and Eston, 2012; Hody et al.,
would increase pennation angle more than eccentric training. 2013b) support the contribution of neurophysiologic processes
In contrast, eccentric-only resistance training seems to favor in the RBE. Indeed, some studies have reported that an initial
fascicle length increase (Reeves et al., 2009), with the implication bout of eccentric exercise in one limb provides protection from
that eccentric training is able to shift the optimum of the the symptoms of EIMD during a second eccentric bout in the
length-tension relationship to longer muscle length (Hoppeler, contralateral limb. Nevertheless, the magnitude of protection
2016). This muscle architectural change appears thus particularly in the contralateral limb is lower than that observed in the
interesting for injury prevention and athletic performance ipsilateral limb, indicating that neural adaptations cannot entirely
(Brughelli and Cronin, 2007). Regarding muscle thickness, explain the RBE (Howatson and van Someren, 2007). Moreover,
similar increases have been observed with both training modes. the demonstration of RBE with electrically stimulated eccentric
There are evidence that eccentric training promotes significantly contractions (Black and McCully, 2008) suggests that the RBE
greater increase in muscle strength, whereas the differences can occur independently of neural adaptations and involves thus
in isometric and concentric measures seems less significant a peripheral and/or muscular adaptation.
(Roig et al., 2009). Findings also showed that the increase in The mechanical origin of initial muscle damage has led
eccentric strength after eccentric training is greater than the authors to suggest that changes in mechanical properties of the
gain in concentric strength after concentric training (Vikne musculoskeletal system could render the muscle more resilient
et al., 2006). The systematic review of Douglas et al. (2017) to EIMD. With respect to this hypothesis, both the passive
also reported mode-specific strength increase and revealed that and dynamic stiffness of the muscle-tendon complex has been
greater overall strength increases can be achieved after eccentric shown to increase after eccentric training (Howell et al., 1993;
training than concentric or traditional training. Furthermore, Reich et al., 2000). These modifications have been, respectively,
in comparison with concentric exercise, eccentric actions have attributed to an increase in intramuscular connective tissue
been reported to induce a greater cross-education effect. Only improving the ability to withstand myofibrillar stress and to
few studies examined changes in muscle power. Performance in a reinforcement of intermediate filament system, in charge of
actions involving muscle power or stretch-shortening cycle (such maintaining the alignment and structure of the sarcomeres
as vertical jump) appeared to be improved to a greater extent (i.e., titin, desmin) (McHugh, 2003). In agreement with the
with eccentric training compared with concentric or traditional reorganization of cytoskeletal proteins, the level of certain
resistance training (Liu et al., 2013; Douglas et al., 2017). structural proteins, such as desmin, was found to increase in
the days following eccentric exercise (Feasson et al., 2002; Lehti
The Repeated-Bout Effect (RBE) et al., 2007). This suggests that muscle-specific cytoskeletal
Skeletal muscle exhibits an intriguing plasticity to repeated remodeling could play a role to protect from future sarcomere
bouts of eccentric exercises. Among the adaptations specifically disruption. Desmin, the major protein of the muscle intermediate
triggered by the eccentric contraction, some contribute to the filament, would act as mechanical integrator for the repair of
RBE, aiming thus to protect muscle against EIMD. A large the filaments (Yu et al., 2002). Its reinforcement secondary to
number of theories have been proposed to explain the RBE, transcriptional upregulation may provide mechanical protection
suggesting a multifactorial origin of this adaptive process. from future sarcomere disruption (Peters et al., 2003). However,
Potential adaptations have been categorized as (Lindstedt et al., some studies showing that stiffer muscles are more prone to
2001) neural, (Abbott et al., 1952) mechanical and (LaStayo et al., damage questioned the mechanical theory (McHugh et al.,
2003b) cellular theories (McHugh et al., 1999a; McHugh, 2003). 1999b). Moreover, desmin knockout (KO) mice have been
However, although many studies have attempted to elucidate the found to exhibit less exercise-induced than wild-type mice (Sam
mechanisms behind the RBE, a unified theory is not yet available. et al., 2000). This finding was, however, imputed to more
According to the neural theory, the EIMD results from compliant muscles of KO mice. Recent works have suggested
the high mechanical stress imposed on a small number of that in addition to their function of structural support to
active muscle fibers during intense eccentric contractions. the cell, the intermediate filaments may play an active role
Although not commonly accepted, this theory also supports in biological processes such as signaling, mechanotransduction
a preferential recruitment of fast-twitch motor units during and gene regulation. The mechanisms behind these processes
eccentric contractions to explain the higher susceptibility to are not well understood. Desmin, which is responsible for
disruption of the fast muscle fibers. Therefore, it has been transmission of stress among myofibrils appears to be required
postulated that changes in neural activation may contribute for the maintenance of myofiber alignment, nuclear deformation,
to reduce subsequent myofibrillar damage (McHugh, 2003). stress production and JNK-mediated stress sensing (Palmisano
Suggested neural adaptations involve improved motor units et al., 2015). Growing evidence supports the role of the
(MUs) synchronization and activation of a large pool of MUs, skeletal muscle intermediate filaments as a stress-transmitting

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Hody et al. Eccentric Exercise

and stress-signaling network. Notably, cytoskeletal proteins help the RBE. A strengthening of the extracellular matrix such as
mitochondria not only in their movement and proper cellular an improved integrin support may help to recover faster after
positioning, but also to maintain their biogenesis, morphology, eccentric contractions (Hyldahl et al., 2015).
function, and regulation of energy fluxes. The functionality of Other potential cellular adaptations include increased protein
these cytoskeletal proteins may thus influence the mitochondria synthesis, adaptation in the excitation-contraction coupling and
functions, including the regulation of Ca2+ signals and apoptosis increased stress proteins (i.e., heat shock proteins) (McHugh,
(Mado et al., 2019). Remodeling of the intermediate filaments 2003). In particular, the role of heat shock proteins (HSPs) in
network may also impact cell migratory behaviors important to protection against muscle damage constitutes an exciting new
development (Sanghvi-Shah and Weber, 2017). area of research. The small HSPs (sHSPs) named HSPB1 (Hsp27)
Another group of theories explaining the RBE relies on and alphaB-crystallin, seem to play important roles in cellular
cellular adaptation. Given the focal feature of muscle damage, adaptation as they have been implicated in the chaperoning of
speculation has been made that the muscle becomes more unfolded proteins, the stabilization of the cytoskeleton as well
resistant to EIMD thanks to the removal of stress-susceptible as in the regulation of the cellular redox state and inhibition
fibers or sarcomeres resulting from the initial eccentric bout of apoptosis (Orejuela et al., 2007). Following one bout of
(Armstrong, 1984; Newham et al., 1987). However, this is eccentric exercise, the sHSPs translocate from the cytosol to the
inconsistent with the fact that the initial bout does not have to cytoskeletal/myofibrillar compartment, presumably to stabilize
cause appreciable damage to confer a protective effect. Several and protect the myofibrillar filament organization (Paulsen et al.,
works provided evidence that eccentric exercise promotes an 2007, 2009; Frankenberg et al., 2014). Such an observation was
increase in series sarcomeres (Lynn and Morgan, 1994; Yu et al., not found after concentric exercise (Frankenberg et al., 2014).
2004). Such longitudinal addition of sarcomeres is thought to AlphaB-crystallin interacts with desmin intermediate filaments
contribute to the protective effect as it would avoid the sarcomere and, Hsp27, together with alphaB-crystallin, has been suggested
stretching beyond their overlap and thus, their disruption. The to interact with various microfilaments (Orejuela et al., 2007).
sarcolemma and sarcoplasmic reticulum would also become These data strongly support the idea that alphaB-crystallin and
stronger following the initial bout of eccentric exercise (McHugh, Hsp27 are crucial for the maintenance and the remodeling of
2003). This may limit perturbations of calcium homeostasis and myofibrillar structures. Therefore, in line with the reinforcement
thus, may prevent the calpain activation and the degradation of the cytoskeletal/myofibrillar structures, appropriate adaptation
of cytoskeletal proteins. The reduced calpain activity could in the protection systems of HSPs might be important as
then explain the attenuation of mitochondrial dysfunction well (Paulsen et al., 2007). Moreover, because the HSPs are
following chronic exposure of eccentric exercise. Other potential involved in the development of stress tolerance against several
adaptations such a decreased susceptibility to calcium-induced stressful insults, it is likely that the HSPs response elicited
mPTP (mitochondrial permeability transition pore) opening or by an initial damaging bout bestows resistance to a second
upregulation of heat shock proteins, in particular Hsp70, may also potentially damaging exercise. Only few studies investigated the
be contribute to protect mitochondrial function (Rattray et al., HSPs response to repeated bouts of eccentric exercise. Paulsen
2013). In addition, changes in the inflammatory response, such as et al. (2009) revealed that two bouts of maximal eccentric exercise
a reduced activation of the monocytes and neutrophils, have been separated by 3 weeks resulted in comparable increased levels of
described after repeated eccentric bouts and may also be related HSPs in the cytoskeletal fraction, despite less damage inflicted
to the RBE (Pizza et al., 1996). Nevertheless, whether adaptation during the second bout. The large amount of Hsp27, alphaB-
in the inflammatory process is the cause or a consequence crystallin, and Hsp70 in the cytoskeletal compartment after the
of reduced muscle damage is not elucidated. Adaptation repeated bout suggests that a more efficient translocation of
may also rely on the monocyte chemoattractant protein 1 these HSPs is plausibly a mechanism behind the RBE. Similarly,
(MCP-1), a chemokine involved in activation and attraction of Thompson et al. (2002) reported a similar relative increase of
inflammatory cells. Indeed, MCP-1 is dramatically overexpressed Hsp27 and Hsp70 2 days after the first and second eccentric bouts,
at the transcript level after a single bout of eccentric exercise and but, intriguingly, the basal levels of these HSPs appeared to be
it appeared even more upregulated after a second bout (Hubal lower before the second bout. This finding casts doubt on the
et al., 2008). Authors have thus suggested that MCP-1 enhances HSPs as important players in the RBE. Contrary to these findings,
muscle recovery after a repeated bout of eccentric exercise via results from a study by Vissing et al. (2009) did not point out a
improved signaling between macrophages and satellite cells. role for the HSPs in reducing EIMD, as they observed a blunted
Other chemokines may contribute to the protective adaptation translocation of HSPs after the second bout. In this latter study,
to exercise-induced muscle damage. Upregulation of CCL2 and the low degree of muscle damage inflicted during the exercise
a decreased of NF-kB DNA-binding activity occur following and/or the long duration between bouts (8 weeks) could explain
repeated bouts of eccentric exercise. These observations supports the lack of HSPs movement following the second bout. Future
the hypothesis that the immune response becomes more efficient studies appear thus to be necessary to delineate the HSPs response
to promote the regeneration of muscle tissue after an initial after repeated eccentric bouts.
bout of eccentric exercises, notably through enhancement in Finally, using a proteomic approach, a short isokinetic
inflammatory cell infiltration into the muscle and myoblast eccentric training in human quadriceps was found to induce
proliferation (Peake J. et al., 2005). Furthermore, a remodeling proteome modifications that suggest an isoform shift in fiber
of the surrounding extracellular matrix might also occur during type components (Hody et al., 2011). Indeed, a decreased

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Hody et al. Eccentric Exercise

expression of several glycolytic enzymes coupled with a lower specific experience and may represent financial constraints. These
expression of the fast isoforms of some contractile and structural reasons may contribute to the few number of studies comparing
proteins was observed after five sessions of submaximal eccentric eccentric training with other modalities and the difficulty to draw
contractions. Adaptation in the muscle fiber typology following definitive conclusions (Julian et al., 2018).
eccentric training was further supported by a study in mice.
This highlighted significant changes in the size and number Competitive Sports
of muscle fiber types following eccentrically biased trained in While few studies have been devoted to the effects of eccentric
comparison with untrained or concentrically biased trained training in elite athletes compared to untrained subjects, the
mice: the eccentric training specifically resulted in an increased systematic inclusion of eccentric-based protocols into training
proportion of slow and fast oxidative muscle fibers (Hody et al., programs is recommended for most competitive sports for
2013a). Nevertheless, whether a shift to a more oxidative muscle performance enhancement or injury prevention purposes (Isner-
phenotype is really involved in protection against EIMD is still a Horobeti et al., 2013; Vogt and Hoppeler, 2014). Indeed, because
question to resolve. of its distinct characteristics, eccentric training modalities can
further enhance maximal muscular strength and optimize
improvements to power, optimal muscle length for strength
MULTIPLE APPLICATIONS OF development, as well as coordination during eccentric tasks
ECCENTRIC TRAINING (LaStayo et al., 2003a). Eccentric training may also be especially
efficient in enhancing speed performance or in rebound activities
Eccentric training has sparked a growing interest over the such as jump (Franchi et al., 2017b; Chaabene et al., 2018).
last decade, particularly in light of the emerging health- This has notably been demonstrated in basketball players. Those
related benefits of improved muscle mass. Moreover, because subjected to eccentric training for 6 weeks exhibited a significant
a greater volume of exercise can be done at less metabolic improvement in jumping height of 8% while the performance
and cardiorespiratory cost, eccentric muscle work constitutes of the players that performed traditional weight-lifting was
a promising training strategy, not only to improve athletes’ unchanged (Lindstedt et al., 2002). A change in titin protein
performances, but also to help maintain or restore the exercise isoform has been proposed to explain the increased stiffness of
capacity and quality of life in individuals with reduced tolerance the muscle-tendon unit and enhanced recovery of elastic strain
for physical activity (i.e., the elderly or patients with chronic energy (Hoppeler, 2016). These functional adaptations in skeletal
disabilities) (Gault and Willems, 2013; Hyldahl and Hubal, 2014; muscles are based on increases in muscle mass, fascicle length,
LaStayo et al., 2014). The lower perceived exertion to perform number of sarcomeres, and cross-sectional area of type II fibers.
eccentric exercises helps to increase the adherence of patients to In terms of injury prevention, the isokinetic assessment of muscle
exercise programs. As eccentric contractions have traditionally function, in particular through the eccentric mode, appears to
been associated with muscle damage, the prescription of eccentric be of great importance for detecting athletes at high risk of
training programs in clinical practice has been discouraged injuries before the start of the season (Croisier et al., 2002;
for a long time. Nowadays, it is well accepted that when Forthomme et al., 2013). Moreover, preventive interventions
the duration, frequency and intensity of the eccentric training with controlled eccentric exercises have been shown to decrease
sessions are progressively increased, symptoms of damage can the risk of hamstring injury in professional soccer players
be minimized and even avoided (Croisier et al., 1999; Chen (Croisier et al., 2008) or of shoulder pain in volleyball players
et al., 2013). Additionally, it is now accepted that neither muscle (Forthomme et al., 2013).
damage nor inflammation are prerequisites for stimulating
positive muscle adaptations as protection against EIMD or Rehabilitation
increased muscle mass (LaStayo et al., 2007). Eccentric training Over the last 20 years, eccentric muscle actions have been
interventions are thus considered as a safe and suitable alternative frequently integrated in the treatment of several pathologies of
to traditional resistance exercise. Before discussing the numerous the locomotor system (Croisier et al., 2009). In particular, chronic
applications of eccentric training, it should be mentioned that eccentric exercise has become a mainstay in the treatment
the identification of its specific effects in comparison to the of tendinopathies mainly of the Achilles, patellar and lateral
other training modalities remain difficult due to methodological epicondylar tendonitis (Croisier et al., 2007; Hoppeler and
reasons. First, the training programs used in several studies Herzog, 2014; Kjaer and Heinemeier, 2014). To justify the
involved usual daily movements that do not isolate eccentric relevance of eccentric exercise for strengthening tendon tissues,
and concentric contractions. Secondly, a limited number of a stimulating impact of such exercise on collagen synthesis and
studies employed an appropriate calibration of the eccentric an increase in blood flow around tendon cells after eccentric
and concentric exercises, making conclusive comparison between actions have been proposed (Guilhem et al., 2010). Eccentric
the contraction modes impossible. Since they imply different intervention has also been shown to be safe and effective after
metabolic cost for the same mechanical work, eccentric and anterior cruciate ligament reconstruction (ACLR). The studies of
concentric exercises must be matched for similar mechanical Gerber et al. (2007, 2009) reported superior short and long-term
output, metabolic rate or oxygen consumption level, or similar results in strength, performance and activity level after surgery
total training load. Additionally, the techniques and equipment when eccentric exercise is part of the rehabilitation after ACL-R
to perform eccentric exercises is often sophisticated, require in comparison to standard rehabilitation programs. Otherwise,

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Hody et al. Eccentric Exercise

ipsilateral eccentric training has been demonstrated to increase elderly subjects submitted to traditional resistance exercises.
muscles’ strength in the contralateral homologous muscle group, Additionally, the subjects of the eccentric group reported the
and this in a greater extent than concentric training (Higbie et al., training to be relatively effortless. Besides resistance training,
1996; Hortobagyi et al., 1997). Thus, implementing unilateral eccentric endurance exercise involving large muscle groups (ECC
eccentric contractions in rehabilitation programs could improve cycling, downhill treadmill walking, and stepping) seems to
the muscle function of the opposite injured limb without it be particularly convenient for the elderly (in particular for
being solicited. frail elderly). This training modality minimizes the substantial
mechanical stress on single joints occurring during resistance
Sarcopenia training and provides benefits for strength, muscle mass and
Given the ever-increasing aging population, the development potentially aerobic adaptations (Gault and Willems, 2013;
of strategies to improve the quality of life of the elderly has LaStayo et al., 2014). The study of Mueller et al. (2009) compared
become a major concern. One of the most evident and disabling the effects of a moderate load eccentric exercise on an eccentric
consequences of aging is sarcopenia, a process characterized ergometer to a conventional resistance exercise training. Both
by a progressive and steady loss of lean skeletal muscle mass. trainings were carried out for 12 weeks with 2 sessions per
Muscle loss is also associated with an increase in intramuscular week. A significant increase in maximal isometric strength (8.4%)
fat and connective tissue, a reduction in muscle strength, in was observed only for the eccentric group (Mueller et al.,
addition to cardiovascular dysfunction reducing aerobic capacity 2009). Improvements in body composition characterized by a
(Gault and Willems, 2013). Such changes contribute to a decrease in intramyocellular lipid content concomitantly with
decline in functional independence and severely compromise total body fat have also been observed in the elderly after
the function, quality of life, and life expectancy in older 12 weeks of eccentric ergometer training (Mueller et al., 2011).
individuals. Multiple lines of evidence suggest that exercise In contrast, tight lean mass increased similarly after both training
training can prevent or reverse muscle aging. Indeed, studies modalities. Interestingly, the gain in muscle mass in the elderly
comparing muscle characteristics of highly trained young and following eccentric training was not paralleled by an increase in
senior athletes demonstrated that trained subjects can maintain muscle fiber cross-sectional area (hypertrophy) as observed with
and improve muscle function regardless of their age (Roig et al., traditional exercise training (Mueller et al., 2011). Muscle growth
2008; Dickinson et al., 2013). However, the implementation of after eccentric training thus seem to occur by the addition of
conventional resistance training programs in the elderly may be sarcomeres in series or by hyperplasia. While available evidence
hampered by the difficulty of such programs as reduced initial suggest that eccentric training protocols are well tolerated in
levels of force and cardiovascular dysfunction are frequent in elderly individuals, it should kept in mind that old adults show
old adults. Conversely, eccentric training programs can massively an increased vulnerability to exercise-related muscle damage.
overload the muscular system with a low cardiopulmonary Indeed, biopsies from the human m. vastus lateralis immediately
stress. Interestingly, numerous studies reported that older after a bout of eccentric cycling showed disorganization of
individuals exhibit a relatively preserved capacity of producing sarcomeres, with a higher percentage of disorganization in
eccentric strength. Indeed, when compared to concentric or older (59–63-years) compared to younger adults (20–30-years)
isometric strength, the magnitude of the age-related decline in (Manfredi et al., 1991). Therefore, careful and safe progression of
eccentric strength is less pronounced. This provides an additional the intensity of eccentric training is thus strongly advised when
advantage for eccentric exercises to initiate resistance training initiating eccentric programs in the elderly.
and rehabilitation programs (LaStayo et al., 2003b; Roig et al.,
2010). In addition to the suitability of eccentric training in old Chronic Diseases
individuals, it is important to emphasize that resistance training Musculoskeletal dysfunction is relatively common in patients
with eccentric contractions induces greater beneficial effects than with chronic conditions such as chronic obstructive pulmonary
concentric training to improve mobility and independence of disease, chronic heart failure or stroke (Hyldahl and Hubal,
the elderly. As in young individuals, high-intensity eccentric 2014). Although the exact etiology of the muscle function
resistance training has been shown to be more effective than decline in these patients is not yet clear, it is believed that
concentric training in increasing muscle strength and mass in the lack of physical activity contributes at least to some
older adults (LaStayo et al., 2003a; Reeves et al., 2009). Other of the deleterious changes in muscle function (Roig et al.,
appreciable benefits resulting from eccentric training in old 2008). Moreover, the ability of exercise to maintain mobility
individuals are the improved ability to complete functional tasks and minimize muscle wasting in most people with chronic
and the decreased risk of fall (Gault and Willems, 2013). LaStayo conditions is commonly accepted. Until now, only few studies
et al. (2003a) demonstrated that using eccentric modality in explored the use of eccentric-biased programs in persons with
very frail elderly (mean age, 80 years) was more efficient to chronic health conditions. Nevertheless, current evidence exists
reverse sarcopenia and its related functional limitations than regarding the effectiveness and safety of eccentric exercise in
traditional weight training. Indeed, the elderly who performed restoring musculoskeletal function in patients with different
10–20 min of eccentric resistance exercise 3 times per week chronic conditions. For instance, compared to conventional
over 11 weeks showed significant improvements in strength training programs, judicious eccentric-based protocols result in
(60%), balance (7%), stair descent (21%) abilities and a reduced greater strength gains and enhancement of functional capacity
risk of fall. These positive outcomes were not found in the in cancer survivors, Parkinson disease patients or total knee

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Hody et al. Eccentric Exercise

replacement patients (Hyldahl and Hubal, 2014). However, dystrophic muscle can partially be accounted for by exhaustive
such favorable effects were not observed in individuals with regenerative cycles (Hyldahl and Hubal, 2014). Nevertheless,
multiple sclerosis (Hayes et al., 2011). Studies exploring the some recent animal studies indicate a favorable adaptation to
use of resistance training in individuals recovering from a moderate exercise in dystrophic animals (Lovering and Brooks,
stroke revealed that eccentric contractions were more effective 2014). In fact, despite the increased vulnerability of dystrophic
for improving neuromuscular activation, strength, and walking (mdx) muscles to eccentric contractions, young mdx mice were
speed than concentric contractions (Engardt et al., 1995; Clark found to recover from and adapt more quickly to EIMD than
and Patten, 2013). Since eccentric training seems to provide wild-type mice (Ridgley et al., 2009; Call et al., 2011). However,
greater central neural adaptation than concentric modes of such increased regenerative capacity was lost in older animals
exercise, the use of eccentric exercise may be particularly (Carter et al., 2002) and it is still unclear whether an eccentric-
effective for patients with central nervous system diseases. The based training program would be helpful or detrimental to the
physiologic characteristics of eccentric contraction (attenuated long-term health of the muscle.
cardiopulmonary stress, low metabolic cost) seem to be well Notwithstanding recent evidence demonstrate the benefits of
suited for their incorporation into the revalidation of patients eccentric training interventions in several fields, there is a real
intolerant to intense cardiac and respiratory efforts (i.e., patients need to further study the physiology of eccentric contraction.
with heart disorders or lung pathologies) (Meyer et al., 2003; Roig Indeed, it is still unclear whether this high specificity of
et al., 2008). Eccentric training has been suggested to attenuate eccentric training adaptations compromises the transferability
reductions in arterial compliance, thus potentially limiting the of strength gains to more functional movements (Roig et al.,
risks commonly associated with resistance training in patients 2010). Moreover, long-term implications of eccentric training
with coronary disease (Okamoto et al., 2006). Steiner et al. (2004) in old individuals or in patients with chronic diseases should
compared concentric and eccentric training at similar heart be explored in more details. Likewise, further investigations
rate (85% of HR) in patients suffering from cardiac problems. are required to optimize parameters as intensity, duration, and
Training was carried out 3 times per week during 8 weeks, modes of eccentric training leading to the favorable effects on
with a progressive increase of the exercise intensity the first muscle performance, health and quality of life.
5 weeks. The authors showed a significant gain in muscle torque
following the eccentric training. Both training modalities induce
a small 3% increase in leg muscle mass but leg and whole PRACTICAL CONSIDERATIONS
body fat mass appeared to decrease only in patients trained
eccentrically. Interestingly, despite working at fourfold higher Eccentric actions can be integrated in different types of
mechanical loads, the eccentric group did not show different muscle training. Plyometric exercises, such as drop jump, is
changes in cardiovascular variables (such as heart rate, mean frequently used to improve speed and jumping ability in athletes.
arterial pressure, or vascular resistance) than the concentrically The literature recommends specific habituation training and
trained subjects (Meyer et al., 2003). Collectively, all studies knowledgeable supervision due to the inherent risk of injuries
reported eccentric exercise to be a safe training modality for in such exercises (Hoppeler, 2016). Eccentric based resistance
patients with various cardiac conditions. training, characterized by high muscle loads at low metabolic
Eccentric exercise may also be useful in the prevention or cost, has been increasingly prescribed for individuals with
treatment of metabolic diseases given its rapid and favorable a centrally limited exercise tolerance (LaStayo et al., 2014).
effects on health related parameters (Roig et al., 2008; However, in most patient populations, the use of high mechanical
Paschalis et al., 2010; Isner-Horobeti et al., 2013). For instance, loads may constrain their adherence to resistance muscle
eccentric training is more effective to improve glucose tolerance training. Therefore, the new modality “moderate load eccentric
than concentric training. Additionally, Paschalis et al. (2010) exercise” represents an attractive choice in various medical
demonstrated that a weekly bout of intense eccentric exercise – conditions (Hoppeler, 2016). Over the last decades, various
and not concentric exercise – is sufficient to improve health risk motorized ergometers or similar devices allowing safe and
factors. They found that only 30 min of eccentric exercise per controlled application of eccentric loads, have been developed for
week for 8 weeks markedly increased resting energy expenditure rehabilitation and performance purposes.
and lipid oxidation as well as decreased insulin resistance The prescription of eccentric muscle training require specific
and blood lipid profile. The study of Marcus et al. (2008) experience. Practitioners must respect fundamental precepts
compared the effects of a 16-week aerobic exercise training and consider important safety considerations concerning the
alone to aerobic exercise combined with moderate load eccentric applications of eccentric muscle training, especially during
exercise in diabetes type 2 patients. While glycemic control and the initial implementation phase. Exercise professionals should
physical performance were similarly improved in all patients, the be aware of the potential detrimental effects of eccentric
improvements in tight lean mass and body mass index were larger contractions as well as the ways to prevent their occurrence.
when eccentric exercise was performed. Nowadays, it is well accepted that repeated exposure to eccentric
In regard with muscular dystrophy pathology, no human exercises confers protective adaptations against potential further
study investigated the potential effects of eccentric training in damage (McHugh, 2003; Nosaka and Aoki, 2011). Even if
this disease. It is likely that eccentric contractions may accelerate the magnitude of this “repeated-bout effect” appeared larger
the degenerative process given that the degenerative nature of if the initial eccentric bout involved high workloads, this

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Hody et al. Eccentric Exercise

strategy could be problematic, especially for those undergoing avoid their onset even in healthy athletes. If EIMD have not
rehabilitation or elite athletes. Indeed, DOMS and the functional been avoided, it is recommended not to perform high intensity
consequences associated with EIMD may frequently disturb the exercises, particularly explosive efforts. Indeed, the risk of
progress of rehabilitation and/or training programs. Moreover, injuries such as muscle tears or ligament rupture has been
the uncomfortable sensations may discourage people to continue shown to increase due to the disturbed muscle function and
exercise training. Therefore, an initial phase consisting of mechanical fragility. Accordingly, it should be kept in mind
submaximal eccentric muscle actions with incremental loading that even when muscle hyperalgesia is resolved, a decrease in
over multiple sessions should be used to introduce individuals muscle function may persist. Care must thus be exerted in
to eccentric muscle training (LaStayo et al., 2003b). Flann et al. the days following an episode of DOMS (Damas et al., 2016).
(2011) demonstrated that a 3-week gradual “ramp up” eccentric When experiencing EIMD, stretching should also be avoided
protocol was effective at promoting muscle hypertrophy in since it could interfere with recovery. Since EIMD triggers
the absence of demonstrable markers of muscle damage. In inflammation response, some practitioners have used non-steroid
clinical interventions, the progressive ramping eccentric protocol anti-inflammatory drugs (NSAIDs) in an attempt to attenuate
typically starts with load of 50–75 W to reach the target the clinical symptoms (Paulsen et al., 2012). Nevertheless, studies
training load of 400–500 W. Higher loads, over 1,200 W, can demonstrated that reducing or blocking potential inflammation
be achieved in competitive athletes (Hoppeler, 2016). A period response may negatively perturb the muscle cell activity and
of 2–4 days between the exposure stimulus and progressively hinder the hypertrophy and regenerative processes (Mackey
higher levels of loading has been suggested as optimal (Hoppeler, et al., 2007). Therefore, NSAIDs should be avoided in healthy
2016). Guidelines to design ramping protocols in rehabilitation subjects (Paulsen et al., 2012). Contrary to this, evidence suggests
conditions are described in more details by LaStayo et al. (2014). that NSAIDs may be beneficial for subjects characterized by
The exercise duration generally increases from 5–10 min to a low-grade systemic inflammation contributing to sarcopenia
20–30 min over the sessions. When using higher load trainings, (Bautmans et al., 2005; Rieu et al., 2009). In the elderly or in
four bouts of 5 min seems to be equally effective and less tiring individuals with chronic disease, the use of NSAIDs may help to
for subjects (Steiner et al., 2004; Vogt and Hoppeler, 2014). maintain muscle mass (Rieu et al., 2009).
A training frequency of two sessions per week seems to be the
lower limit to induce measurable gains (Mueller et al., 2009).
When conceiving eccentric interventions, practitioners should CONCLUSION
also take into account the parameters affecting the extent and
duration of EIMD and/or slower recovery. Exercises performed at The study of eccentric contraction is no longer confined to
high vs. low eccentric torque, at long vs. short muscle length and muscle physiology and sport sciences but is becoming central
increasing numbers of eccentric contractions appear to result in in clinical medicine and is likely to expand in the near future.
more severe EIMD (Nosaka and Newton, 2002). Skeletal muscles Indeed, due to its unique neural, mechanical and metabolic
do not display the same vulnerability to EIMD. The upper limb properties, the eccentric mode has gained a growing interest in
muscles appear mostly more affected than lower limb muscles several fields. In addition to its efficiency in sports performance
and the knee flexors more than the knee extensors (Chen et al., and rehabilitation, the eccentric training interventions constitute
2011). The untrained status, genetic variations, aging and chronic an attractive strategy to prevent muscle wasting in sarcopenia
diseases are other factors increasing the severity of potential or in many chronic diseases. Increasing evidence also support
EIMD (Tidball, 2011; Gault and Willems, 2013; Baumert et al., the beneficial effects of eccentric exercises on body composition
2016). Special attention should thus be given to these populations and other health-related parameters, making this contraction
when establishing the initial eccentric exercise prescription in mode a promising tool for various patient populations. However,
rehabilitation settings. unaccustomed eccentric exercise is well known to induce muscle
Even if trained athletes are generally less affected by EIMD damage that manifests by a range of clinical symptoms including
than untrained people when submitting to the same eccentric DOMS and decreased muscle function. Up to now, there is no
protocol, they might not escape to the detrimental effects of equivocal therapeutic approach allowing a significant attenuation
eccentric contractions in some circumstances. They might be in the symptoms of damage. Conversely, it has been clearly
particularly vulnerable to EIMD at the start of the season, demonstrated that repeated exposures to eccentric actions with
or when they return to competition after injury or following progressively increasing loads can prevent the occurrence of
an unaccustomed eccentric session (Cheung et al., 2003). The muscle damage or DOMS.
occurrence of EIMD associated with unaccustomed eccentric
exercise could be problematic in athletes because of the
associated negative consequences on locomotor biomechanics FUTURE PERSPECTIVES
and sport performance within the short term (Cheung et al.,
2003; Assumpcao Cde et al., 2013). Moreover, when athletes Although the eccentric contraction has received more attention
suffered from DOMS, they are frequently unable to train at over the last decade, many questions remain unanswered with
their maximal intensity which can compromise the quality regard to both the initial damaging response to unaccustomed
of the training programs. Even if the negative functional eccentric contraction and the subsequent adaptations. Further-
consequences of EIMD are transitory, it seems important to more, the mechanisms behind the protective effect conferred

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Hody et al. Eccentric Exercise

by a repeated eccentric bout are still in great part speculative. draw guidelines for eccentric activity prescriptions. In particular,
Yet, the numerous practical applications of eccentric exercise more efforts should be devoted to develop intensity, duration and
in sports, rehabilitation and pathological conditions justify the modes of eccentric training optimizing efficiency of this method.
need to elucidate the mechanisms underlying the acute and
chronic effect of eccentric exercise on the skeletal muscle.
In addition, a better knowledge of the transient eccentric induced AUTHOR CONTRIBUTIONS
damage and subsequent adaptations on a mechanistic level
may help to further understand the degeneration/regeneration SH wrote the manuscript. J-LC, TB, BR, and PL revised the
cycles in healthy skeletal muscle and to identify abnormalities in manuscript according to their respective field of expertise.
these processes in pathological conditions as in neuromuscular
diseases. Given some similarities in the histopathological
alterations that follow unaccustomed eccentric actions with FUNDING
those observed in muscular dystrophy pathology, further
investigations on the eccentric exercise may unravel crucial issues This work was supported by “Fonds de la Recherche
in molecular mechanisms frequently involved in neuromuscular Scientifique Médicale” grant (FRSM 3.4559.11) from the Belgian
diseases. Investigations employing rigorous standardization of “Fonds de la Recherche Scientifique-Fonds National de la
the experimental conditions in the eccentric and other training Recherche Scientifique” (F.R.S.-FNRS). PL is a Senior Research
groups are necessary to determine the specific multi-target and to Associate of F.R.S.-FNRS.

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Eccentric exercise-induced morphological changes in the membrane systems Copyright © 2019 Hody, Croisier, Bury, Rogister and Leprince. This is an open-access
involved in excitation-contraction coupling in rat skeletal muscle. J. Physiol. article distributed under the terms of the Creative Commons Attribution License
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eccentric exercise-induced damage to toad skeletal muscle. J. Muscle Res. Cell publication in this journal is cited, in accordance with accepted academic practice. No
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