Introduction to Basic Pharmacology and

Other Common Therapies & Pain

Gould
Chapters 3 & 4

Week 3
Outline: Chapter 3
• Define common terms used in pharmacology.
• Differentiate the types of adverse reactions.
• Explain the factors that determine blood levels of a drug.
• Compare the methods of drug administration.
• Describe the difference between the terms dose and dosage.
• Describe the role of receptor sites in drug action.
• Differentiate a generic name from a trade name.
• Explain the basis for the various legal restrictions on the sale of drugs
listed in different schedules.
• Describe the roles of specified members of the health care team,
traditional and alternative.
• Describe the basic concepts of Asian medicine.

Images from Gould’s Pathophysiology for the Health Professions, 5th ed., © 2014, by VanMeter & Hubert,
denoted by “Go”.
Outline: Chapter 4
• State the causes of pain.
• Describe the pain pathway.
• Relate the methods of pain control to the gate-control
theory.
• Discuss the signs and symptoms of pain in adults and
young children.
• Compare referred and phantom pain.
• Explain the factors that may alter pain perception.
• Compare acute and chronic pain.
• Discuss the types of headache.
• Describe methods of pain management.

Images from Gould’s Pathophysiology for the Health Professions, 5th ed., © 2014, by VanMeter & Hubert,
denoted by “Go”.
Pharmacology
• Integrated medical science
involving chemistry,

http://www.crafthubs.com/poppy/7282
biochemistry, anatomy,
physiology, microbiology, &
others
• Study of drugs, their actions,
dosage, therapeutic uses or
indications, adverse
effects
• Drug therapy is directly linked to
the pathophysiology of a particular
disease

en.wikipedia.org
Drugs
• Substances that alter biologic activity of people – even
placebo
• Drugs may come from natural sources (plants,
animals, microorganisms, i.e. fungi) or can be
synthesized (may have originated from natural
substances)
• Administered to:
• Promote healing (e.g. anti-inflammatory)
• Cure disease (e.g. antibacterial)
• Control or slow progress of a disease (e.g. chemotherapy)
• Prevent disease (e.g. vaccines)
• Increase comfort levels (e.g. analgesic for pain)
• Decrease risk of complications (e.g. anticoagulants)
• Use as replacement therapy (e.g. insulin)
• Reduce excessive activity in the body (e.g. antianxiety/sedatives)
Pharmacology is organized into separate disciplines that deal
with actions of drugs:

• Pharmacodynamics: Drug-induced responses of physiologic

and biochemical systems
• Pharmacokinetics: Drug amounts at different sites after
administration
• Pharmacotherapeutics: Choice and drug application for
disease prevention, treatment, or diagnosis
• Toxicology: Study of the body’s response to drugs, harmful
effects, mechanisms of actions, symptoms, treatment, and
identification
• Pharmacy: Preparation, compounding, dispensing, and record
keeping of therapeutic drugs
Drug Effects
• Classification
• Grouped by their primary pharmacologic action & effect
• Indications of a drug
• Approved uses to treat conditions that the drug has been proved to
be effective
• Off-label uses: those for which the drug has shown some
effectiveness, but not the use for which the drug was approved by
regulatory bodies. Can anyone think of a medication that has been
in the news recently for being used for an off-label use?
• Contraindications
• When the drug should not be taken
• Side effects
• Mild, undesirable effects of a drug (even at recommended doses)
• Adverse or toxic effects
• Drug effects that are dangerous, cause significant tissue damage, or
are life threatening
Specific Adverse Drug Effects
• Hypersensitivity – allergic reaction
• Reactions may be mild or result in anaphylaxis
• Idiosyncratic (paradoxical)– unexpected or unusual
response to a drug – unique to the patient
• Iatrogenic – negative effect associated w/ administration of
drug (medication error, drug overdose, negative medication
interaction)
• Teratogenic – harmful effect on fetus è developmental
defects

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Adverse Drug Effects: Interactions
• Interactions – occur when drug effect modified by a
combination w/ another drug, food, herbal compound
• Synergism
• Effect of drug combination may be greater than the sum of the
effects of the individual drugs (highly increased effect), can be
life threatening, e.g. causing hemorrhage or coma or could be
beneficial, e.g. combining drugs to treat pain.

• Antagonism
• Combination greatly decreases the effect of one or both drugs.
Is beneficial when an antidote is required for an accidental
poisoning or overdose
• Potentiation
• One drug enhances the effect of a second drug
• Epinephrine & local anesthetic prolongs effects of latter
Administration & Distribution of Drugs
• Dose
• The amount of drug required to produce the desired effect at
a single time, expressed by a weight or measure (e.g. 200 mg
ibuprofen)
• Dosage refers to the total amount of the drug given over a
period of time, expressed by time factor (e.g. 1-2 tablets every 4
hours)

• Child’s dose – calculated by child’s weight, not age

• Loading dose – larger dose administered initially to raise
blood levels to an effective level quickly
• Often w/ antimicrobial drugs
Administration & Distribution of Drugs
• Frequency of dosing
• Important to maintain effective blood levels of the drug
w/out reaching toxic levels
• Optimum dosing schedule
• Established for each drug based on
• Absorption, transport in the blood, half-life of the drug,
and biotransformation (chemical alteration by various
bodily systems to create compounds that are more easily
excreted from the body, occur primarily in the liver)
• Want regular intervals over 24hr day
• Timing – directions regarding
• Timing related to meals (e.g. insulin)
• Daily events
• Sleep (e.g. melatonin)
• Intentional
Factors Affecting Blood Levels of Drugs
• Dependent on:
• Time it takes for drug to be absorbed by body
• When drug was administered
• Drug dosage
• Amount of drug excreted

Go3.1
Factors Affecting Blood Levels of Drugs
• Regular intake, normal distribution &
excretion, e.g. Tylenol 200 mg q6hours

Go3.1
Factors Affecting Blood Levels of Drugs
• Taking drug at irregular intervals, missing doses
Factors Affecting Blood Levels of Drugs
• Taking double dose or too frequently
Factors Influencing Blood Levels of a Drug
• Circulation & cardiac function

• Age
• Gender
• Body weight & proportion of fatty tissue

• Activity level/exercise

• Ability to absorb, metabolize & excrete drugs (liver & kidney

function)
• Food & fluid intake
• Genetic factors
• Health status/presence of disease – chronic or acute
Drug Administration
Drugs can be administered for local or systemic action:

• Local administration includes topical application to the skin,

application to the mucous membranes, oral administration,
inhalation for selected respiratory conditions, etc.

• Systemic administration routes include transdermal, oral,

sublingual, transdermal, rectal (suppository), inhalation,
subcutaneous or intramuscular injection, intravenous injection,
and intrathecal injection (injection through the sheath
meninges around the spinal cord into the subarachnoid space).
Routes of Drug Administration
A. Oral – tablet, capsule, liquid (slowest route) (PO)

B. Sublingual – under tongue (SL)

C. Parenteral (injection)
• Subcutaneous (SC/SubQ) – below dermal skin layer (insulin)
• Intramuscular (IM) – gluteus or deltoid (immunizations)
• Intravenous (IV) (quickest route) – vein (analgesia)
• Intradermal (ID) – dermal skin layer (allergy, TB skin test)
• Intrathecal (IT) – below meninges (chemo for leukemia)
Routes of Drug Administration
D. Inhalation – respiratory tract (asthma)

E. Topical (gel, cream, spray, liquid) – skin or mucous

membrane (antiseptics)
• Transdermal (TD) – applied on skin but drug
administers continuously through skin to blood
(nicotine patch), Fentanyl

F. Suppository – vaginal or rectal (laxative)

G. Otic – ear (anti-infective ear drops)

H. Ophthalmic – eye (eye drops)

Routes of Drug Administration

Subcutaneous
Intramuscular

Epidermis
Dermis
Intradermal
Subcutaneous
tissue
Muscle

diabetesindogs.wikia.com
Routes of Drug Administration
• Some drugs can only be taken via one route and
others can be taken in various routes

Tylenol can be taken IR or PO. Why would we give

Tylenol rectally?

We can give antihistamines like Benadryl PO or IV. Why

would we choose to give it IV?

Considerations to improve ‘compliance’:

• time-release or long-acting forms
• Enteric-coated
• What else could impact ‘compliance’?

Go3.2
Drug Absorption, Distribution & Excretion
• Absorption – movement of drug from administration site to one
or more body membranes
• Usually takes place in mucosa of stomach, mouth, small intestine or
rectum
• Also blood vessels, muscles, subcutaneous tissues, skin

• Conditions that may alter process

• Size of drug particles

• Physical state of drug particles

• Drug properties

• Presence/absence of food in digestive tract

• Membrane thickness, surface area, how cellular membranes
connected

• Bloodstream – binding to plasma proteins

• Body temperature
Drug Absorption, Distribution & Excretion
• Distribution – how drugs are transported throughout the
body
• Circulatory system, through capillaries & across cell
membrane
• May be adversely affected by poor circulation which may
prevent drug from reaching site (e.g. shock)
• Physiological barriers may hinder distribution (BBB, placenta)

mastermindegg.xyz
Drug Absorption, Distribution & Excretion
• Metabolism – where drugs are made more or less active
• Primary site – liver, but can occur in almost every cell
• Different conditions can impede metabolism (age, disease,
genetic effects)

• Excretion – how drugs are removed from body

• Occurs in kidneys, sweat glands, lungs, breast milk, feces or
bile
Drugs & Receptors
• Drugs may stimulate
receptors directly
• Drugs may block
receptor site for normal
chemicals of body
• Specificity of drug is
dependent on mode of
action
• Drugs that interact w/
several metabolic
pathways or common
functions are likely to
have greater side
effects

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Drug Response
Once a drug is administered to the human body, it will
produce a series of responses, which can be divided into
four categories:

1. Dose effects: goal to produce the desired positive effects and

minimize the potential toxic effects, will vary by patient
2. Time effects: will affect the magnitude of the response to the
dose given. The time response itself measures time of
administration, onset of response, peak effect, toxicity, etc.
3. Variability: variables that influence the biotransformation and
eventual elimination of the drug, i.e. chemical properties, toxic
effects, liver & kidney disease, etc.
4. Toxicity: an effect that is harmful to a biologic system; n includes
the following characteristics: physiochemical properties, routes
and rates of administration, etc.
Prescriptions
• Prescribed by doctors, nurse practitioners (some),
dentists, veterinarians, etc.
• Is a signed legal document that must include
1. Patient name, address, age
2. Prescriber’s name, address, & identification number
3. Date
4. Name & amount of drug
5. Dosage
6. Route & directions for using the drug (e.g. po tid = orally 3
times/day)
7. Permission for additional quantities
• Sometimes information is abbreviated – familiarize yourself
with common abbreviations (found at the end of textbook)
• Over the counter medications (OTC) don’t need physician
order
• Usually not harmful at the dosages that are available w/out
prescription
Drug Nomenclature
• Each drug has:
1. Chemical name is the chemical component of drug –
acetylsalicylic acid (2-(acetyloxy)benzoic acid)
2. Generic name is unique, official, simple name for a specific
drug – ASA
• Similarities indicate a family of drugs w/ similar actions (e.g.
benzodiazepines – antianxiety agents) – classification
3. Trade/Product name is proprietary, or brand name – Bayer
Aspirin
Drug Regulation
• Food & Drug Act & its regulations are Canada’s federal
legislation
• Ensures quality & drug safety
• Indicates who has access to controlled or restricted drugs,
how drugs are stored, accounting of drug administration,
labeling (restricted/controlled drug)
• Full Regulations: https://laws-lois.justice.gc.ca/eng/acts/f-
27/
• Each drug is assigned one or more schedule (category)
according to the Food & Drug Regulations, & the
Controlled Drugs & Substances Act (https://laws-
lois.justice.gc.ca/eng/acts/c-38.8/)
• Refer to “Drug Schedule Definitions”
• Specific schedule dependent on drug effect & potential effect
Drug Regulation
• Drugs listed in Food & Drug Act
• Prescription (prescription drugs included in the Prescription
Drug List)
• Schedule/Part G – controlled
• Amphetamines, pentobarbital, barbiturates (CNS depressants),
anabolic steroids

• Schedule/Part J – restricted
• Thienyl cyclohexyl piperidine (TCP), mescaline (hallucinogen),
lysergic acid diethylamide (LSD)

• For existing & developing drugs

Traditional Forms of Therapy
• May be involved either directly or indirectly in the
team approach to care of a patient who may be a
hospital inpatient, an outpatient, or someone in the
community.

• Therapies must address the pathophysiologic changes

if a return to health is to result or function is to
improve with minimal complications.
Traditional Forms of Therapy
Physiotherapists (PTs): assess physical function, work to restore any deficit
and prevent further physical dysfunction.

• individualized treatment and rehabilitation, as well as approaches to reduce pain

resulting from disease, surgery, or injury.
• may include appropriate exercises ultrasound, transcutaneous electrical nerve
stimulation, or other methods to alleviate pain and increase joint flexibility and
mobility.
• work with patients with acute neurologic, musculoskeletal, and cardiopulmonary
disorders. i.e. Infants with congenital defects or children with injuries affecting
mobility
• major areas for physiotherapy are rehabilitation and long-term care, in which the
focus is on maximizing mobility and functional independence.
• Chest therapy to mobilize excess secretions and aid lung function for
postoperative patients, those with COPD, bronchiectasis, or cystic fibrosis.
• Educating patients and families to assist with and maintain their individual
programs
• Physiotherapy aides or assistants may take on some responsibilities under the
supervision of a registered physiotherapist.
Traditional Forms of Therapy
Occupational therapists (OTs):
• provide a functional assessment of patient capabilities related to normal
activities of daily living (ADLs), includes an evaluation of motor, cognitive,
and visual-spatial ability.
• has expertise in teaching the client to use adaptations in meeting his or
her needs. This includes assessment of technologies available in the
marketplace, their effective use, and appropriateness for the particular
client.
• work directly with technicians in the production of aids such as
wheelchairs or walkers, as well as adaptive devices for food preparation,
feeding, and personal hygiene.
• In the workplace setting, work along with occupational health personnel
to assess the workplace and essential tasks, identify appropriate
accommodation, and instruct clients in the effective and safe use of
supportive technologies.
Traditional Forms of Therapy
• Speech/Language Therapist: specialist in the assessment and treatment
of those with communication or swallowing problems, i.e. an infant with
swallowing and feeding problems, a child with a hearing deficit who is
mute, an adult with aphasia after a stroke, or someone requiring a
hearing assessment.

• Nutrition/Dietician: As an expert in foods and the nutritional needs of the

body in health and illness, offers advice to individuals or groups on the
nutritional demands and food management best suited to a specific
diagnosis (e.g., diabetes); supervise food services in hospitals, other
health care institutions; may be consulted regarding the dangers of
extreme diets or eating disorders such as anorexia nervosa.

• Registered massage therapists: use a variety of techniques to increase

circulation, reduce pain, and increase flexibility for clients experiencing
join pain or problems with body alignment; may also use soothing
aromatics, acupuncture, or other modalities during therapy.
Traditional Forms of Therapy
• Osteopaths: medical doctors who use all the traditional
treatment methods such as surgery and drugs, but in
addition they promote the body’s natural healing processes
by incorporating manipulations of the musculoskeletal
system in both diagnosis and treatment.

• Chiropractic medicine: based on the concept that one’s

health status is dependent on the state of the nervous
system, which regulates all body functions to maintain
homeostasis. Practice frequently involves manipulation of
the vertebral column. Although no drugs or surgery are
included in chiropractic therapy, acupuncture may be used.
 Complementary or Alternative Therapies
• Therapeutic practices considered to be outside the range of
traditional Western medicine that also focus on alleviating disease
and suffering, have gained some general acceptance and are
termed complementary, used in conjunction with Western medical
therapy
• Naturopathy: promoting natural foods, massage, exercise, and fresh air as a
way of life, thus enhancing health and preventing disease.
• Homeopathy: goal of stimulating the immune system
and natural healing power in the body through the use of plant, animal, and
mineral products.
• Herbal Medicine: use herbs and plants for medicinal purposes, i.e. echinacea
as a cold remedy
• Aromatherapy: use of essential oils that have therapeutic effects when
rubbed on the skin or inhaled are extracted from plants.
Herbal Medicine
Complementary or Alternative Therapies
Asian Concepts of Disease and Healing
• based on the balance or imbalance of life energy called qi in Chinese
medicine (also called ch’i or chi, pronounced chee) or ki in Japanese
medicine.
• Acupuncture: a Chinese therapeutic discipline that is over 3000 years
old and involves inserting very fine needles into the various meridian
acupoints to balance the body energy.
• Shiatsu (Japanese: finger pressure): the Japanese-refined version of
Chinese anma massage, or acupuncture without needles.
• Yoga: an ancient Indian discipline of various forms that combines
physical activity in the form of body stretching postures (asanas)
with meditation.
• Herbal Medicine
Pain
Chapter 4
Pain
• an unpleasant sensation, a feeling of discomfort resulting
from stimulation of pain receptors in the body when tissue
damage occurs or is about to occur.
• a body’s defense mechanism and is a warning of a problem,
particularly when it is acute.
• difficult to define because it can have many variable
characteristics, and it is a subjective feeling, impossible to
accurately measure.
• In cases of trauma, the danger may be obvious, but in other
situations the cause may be hidden deep inside the body.
• involves complex mechanisms, many of which scientists and
health care workers do not totally understand.
Etiology and sources of pain
• May occur for many reasons: infection, ischemia and tissue necrosis,
stretching of tissue, chemicals, or burns. In skeletal muscle, pain may
result from ischemia or hemorrhage.
• Many organs such as the liver, kidney, or brain are characterized by
pain receptors in the covering capsule, and pain is felt when the capsule
is stretched by inflammation.
• Stretching of tendons, ligaments, and joint capsules; may occur
secondary to inflammation or muscle spasm to guard a joint or painful
body part.
• In the stomach and intestines, may result from inflammation of the
mucosa, ischemia, distention, or muscle spasm.
• Somatic pain may arise from the skin (cutaneous) or from deeper
structures such as bone or muscle, conducted by sensory nerves.
• Visceral pain originates in the organs and travels by sympathetic fibers.
• Depending on the cause, pain may be sudden and short-term, marked
primarily by a reflex withdrawal.
Pain
• Pain threshold –level of stimulation required to activate the
nerve ending sufficiently for the individual to perceive pain.
The associated nerve fibers then transmit the pain signal to
the spinal cord and brain.

• Pain tolerance – ability to withstand pain or the perception of

its intensity is referred to as pain tolerance; can vary with past
pain experience and overall state of health.
Pain Pathways
• Nociceptors = pain receptors, are free sensory nerve endings that are
present in most tissues of the body. May be stimulated by several means:
• Thermal (extreme temperatures)
• Chemical (acids or compounds produced in the body, such as
bradykinin, histamine, or prostaglandin);
• Mechanical/physical, i.e. pressure

Pain transmitted via 2 afferent fiber types:

A. Myelinated A delta fibers
• Transmit impulses very rapidly
• Acute pain
• Sudden, sharp, localized
B. Unmyelinated C fibers
• Transmit impulses slowly
• Chronic pain
• Diffuse, dull, burning, or aching sensation
 Physiology of Pain and Pain Control
• Gate-control theory
• “Gates” built into normal pain
pathway è help modify pain
stimuli conduction/ transmission
in spinal cord & brain
• Gates “open” = pain travels
through
• Gates “closed” = pain
blocked/reduced
 Characteristics of Pain
Possible details that may be helpful in diagnosing the severity
and cause of pain include the following (can use OLD CARTS):

• The location of the pain

• Descriptive terms: aching, burning, sharp, throbbing, widespread,
cramping, constant, periodic, unbearable, or moderate
• Timing of the pain or its association with an activity such as food intake
or movement, or with pressure applied at the site
• Physical evidence of pain, demonstrate a stress response with physical
signs such as sweating, high blood pressure, or tachycardia (rapid heart
rate)
• Nausea and vomiting or fainting (vasovagal response) and dizziness
• Anxiety and fear, which are frequently evident in people with chest pain
but may be present in other situations as well
• Clenched fists or rigid faces; restless or constant motion, or lack of
movement; often protecting, or “guarding,” the affected area
Referred Pain
• Source may be difficult
to determine
• Pain may be perceived
at site distant from
source
• Common w/ visceral
damage in the
abdominal organs
• Heart attack or
ischemia in the heart

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Phantom Pain

• Pain or another sensation such as itching or tingling

occurs in some individuals, usually adults, after an
amputation.
• Perceived by the person as occurring in the lost
limb and typically does not respond to usual pain
therapies.
• Pain may resolve within weeks to months. Although
the phenomenon is not fully understood, it appears
that the brain “understands” the limb to still be
present when processing incoming stimuli.
Pain Perception and Response
• Subjective and depend on the individual.
• Factors such as age, culture, family traditions, and
prior experience with pain shape one’s perception
and response to pain.
• Individual’s temperament, personality can
influence the response to pain, and the
circumstances existing at the time of the incident
may affect perception of it.
• Anxiety, fear, and stress can increase the severity
of pain (CNS is at a higher level of awareness).
• Fatigue, hunger, and the presence of other
pathologies or problems may magnify a person’s
response.
Headache
• Common type of pain. There are many categories of headache associated
with different causes, and some have specific locations and
characteristics.
• Can be due because of congested sinuses, nasal congestion, and
•
eyestrain are located in eye and forehead areas.
Sinus headaches can be severe. These headaches are usually steady and are relieved when the cause is removed.

• Tension headaches associated with muscle spasm result from

emotional stress and cause the neck muscles to contract to a
greater degree, pulling on the scalp.
• Headache in the temporal area is often associated with
temporomandibular joint syndrome, in which the underlying
cause is a malocclusion involving the jaw or inflammation of the
joint caused by arthritis or poor body alignment, which causes
muscle tension in the neck that is transferred to the jaw.
Headache
• Migraine headaches are related to abnormal changes in blood
flow and metabolism in the brain, but the exact mechanism is not
yet fully understood, usually throbbing and severe and is often
incapacitating. Characteristically, migraine headaches begin
unilaterally in the temple area, but often spread to involve the
entire head; pain is often accompanied or preceded by visual
disturbances and dizziness, nausea and abdominal discomfort,
and fatigue.
• Intracranial headaches result from increased pressure inside the
skull, any space-occupying mass stretches the cerebral vascular
walls or the meninges covering the brain. Causes include pressure
include trauma with edema or hemorrhage, tumors, infections
such as meningitis, or inflammation resulting from toxins such as
alcohol.
Basic Classifications of Pain
Central Pain:
• caused by dysfunction or damage to the brain or spinal cord.
• a lesion such as abscess, infarction, hemorrhage, tumor, or damage
resulting from direct injury
• can be localized or can involve a large area of the body.
• persistent, irritating, can cause considerable suffering over an extended
period of time.

Neuropathic Pain:
• caused by trauma or disease involving the peripheral nerves.
• can vary from a tingling to a burning or severe shooting pain.
• Exacerbated by Movement, injured nerves that can become
hyperexcitable, and some neurons with low thresholds for thermal,
mechanical/physical, or chemical stimuli may spontaneously fire. i.e.
neuralgias are examples of extremely painful conditions that are a result
of damage to peripheral nerves caused by infection or disease.
Basic Classifications of Pain
Ischemic pain:
• Results from a profound, sudden loss of blood flow to an
organ or tissues in a specific area of the body; decreased
blood supply results in hypoxia, leads to tissue damage and
the release of inflammatory and pain-producing substances.
• description may vary from aching, burning, or prickling to a
strong shooting pain (particularly in an extremity).
• symptoms depend on the location of the hypoxic tissue, can
be characterized as either acute or chronic pain. i.e
atherosclerotic disorders that cause blocking of arterial flow
can cause ischemic pain, particularly in the lower extremities.
Basic Classifications of Pain
Cancer-Related Pain
• Often associated with pain, usually chronic pain; broken down into
several categories:
• Pain caused by the advance of the disease and resultant
damage to the body (most common). As the tumors grow, they
can cause infections and inflammation, which in turn cause
increased pressure on nerve endings, stretching of tissues, or
obstruction of vessels, ducts, or the intestines. This type of pain
may be characterized as acute with sudden onset, intermittent,
or chronic, persisting over a long period of time.
• Pain associated with the treatment of the disease
• Pain that is the result of a coexisting disease unrelated to the
cancer
Methods of Managing Pain
• Remove source of pain ASAP

• Use of analgesic medications

• Use adjunct therapies including sedatives and anti-

anxiety drugs
Intractable pain

• Pain that cannot be controlled with medications, surgical

intervention is a choice.
• Procedures such as rhizotomy or cordotomy to sever the
sensory nerve pathway in the spinal nerve or cord may be
done. Injections can be given with similar effects, carry risk
of interference with other nerve fibers and functions,
particularly when the spinal cord is involved.
Anesthesia