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Focus on Pain Management • Par t 1
Continuing Education
Focus on pain management: Physiology of pain
This first article in a three-part series provides an overview of the physiology of pain. Topics include pain perception;
Learning Objectives
various factors influencing pain; classifications of pain by source, duration and intensity; and pain assessment.
Michael Ashburn, MD, MPH, vice president for clinical and regulatory affairs, ZARS Inc., Salt Lake City, UT; and
Describe the physiology
behind pain perception.
Arthur G. Lipman, PharmD, professor of pharmacotherapy, College of Pharmacy, adjunct professor of anesthesiology,
School of Medicine, director of clinical pharmacology, pain Management Center, University of Utah Health Sciences
Identify different factors
that can influence pain.
Center, editor, Journal of Pain & Palliative Care Pharmacotherapy, Salt Lake City, UT, served as consultants for
this article for the Certified Medical Representatives Institute Inc.
Explain how pain is
classified by source.
Explain how pain is
classified by duration
and intensity.
Describe how pain is
assessed in different
situations.
etween a site of active tissue damage and
the perception of pain lies a complex
series of electrochemical events, collectively called nociception. A nociceptor
may be defined as a type of nerve ending
that generates an impulse in response to a noxious
or potentially noxious stimulus. This impulse initiates the process perceived as pain when it reaches
the brain.
The perception of and response to pain are
widely believed to be determined by four distinct
processes. All are required for nociceptive pain
to occur:
Transduction. The first of these processes is
transduction, which occurs when a noxious, painful
or tissue-damaging stimulus affects a peripheral sensory nerve ending, depolarizing it and generating
the initial electrical impulse.
Transmission. The next process is transmission,
which involves the subsequent neural events that
“carry” the impulse throughout the nervous system; the spinothalamic tract is the most important
pathway for transmission.
Perception. Perception occurs when the nociceptive impulse reaches the cerebral cortex.
B
Modulation. Modulation is the body’s physiologic response to the perception of pain, involving neural activity on both ascending and
descending neural pathways. It may increase or
decrease the intensity and duration of the pain
experience (for example, by triggering the release
of endorphins, which may lessen the experience
of pain).
The gate control theory is a widely accepted
theory on the mechanism of pain transmission.
According to this theory:
• Nerve impulses are modulated in the spinal
cord by a spinal gate mechanism.
• The spinal gate mechanism is influenced by
large and small fiber activity, as well as descending control modulation from the brain.
• A central control trigger system activates
cognitive processes.
Activation of peripheral receptors by mechanical or chemical stimuli excites discharges in two
distinct types of nerve fibers:
• Fast-acting A-delta fibers, responsible for transmitting acute, intense, short-lasting pain.
• Slower-acting C-fibers, involved in the transmission of burning, deep, long-lasting pain.
RECEIVE CREDIT AND RECOGNITION
Continuing Education in Pharmaceutical Representative aims to provide reps with information to help them meet
the needs of the people they serve and to contribute to reps’personal and professional development.Every third
issue includes a self-assessment quiz covering the previous three Continuing Education articles. The quiz for
this article will appear in the June issue. Reps who correctly complete the quiz and return it to the CMR Institute
with a nominal handling fee will receive a completion recognition form showing that they have successfully completed the three-part educational series and earned .25 CEU (2.5 contact hours). The CMR Institute also will
send a letter of recognition to reps’ managers upon completion of a quarterly series. A Certificate of Achievement will be awarded to any representative who successfully completes four quizzes or has obtained 1.0 CEU.
Note: The Continuing Education quizzes are not part of CMR Institute’s certification program and do not count as
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About the CMR Institute:
The Certified Medical Representatives Institute is an independent non-profit educational organization established in 1966 to provide a source of professional development and certification for pharmaceutical representatives. The institute provides an up-to-date, approved continuing education curriculum designed to
expand and enhance internal company training and development in a cost-effective manner. The curriculum concentrates on providing a general knowledge base and avoids such areas as selling skills and
specific product education.
© 2007 The Certified Medical Representatives Institute Inc., Roanoke, VA 24014. All rights reserved.
No part of this article may be reproduced by any method or in any form without written permission from the CMR
Institute. Reprints of this article are available from the CMR Institute. Request Continuing Education article FP-1.
Pharmaceutical Representative www.pharmrep.com | April 2007
These primary sensory fibers enter the dorsal root
of the spinal cord and are conducted into the dorsal horn — the so-called spinal gate. These various
influences, together, determine whether nociceptive
signals travel to the brain and to what degree pain is
experienced consciously. When the output of
nerve cells in the spinal cord exceeds certain limits,
an action system is activated, causing complex patterns of pain experience.
Gate control theory
Influences on pain
Many factors can influence one’s experience of pain;
several are described below.
Continuous noxious stimulation. The central
nervous system (CNS) may actually change its whole
cascade of responses in response to this type of
stimulus. In the case of a traumatic injury or serious
disease, where the body is unable to completely heal
itself, the nervous system may be unable to return
to a state of homeostasis. Thus, chronic pain is often
perpetuated by factors other than the original injury
or disease, which may have healed. In chronic pain
syndromes, the degree of pain is often not proportional to the original injury. This is frequently the case
with low back pain and the chronic pain of postherpetic neuralgia and fibromyalgia. The use of cognitive and behavioral therapies for chronic pain (such
as biofeedback and hypnosis) can frequently alter the
patient’s perception of his or her pain. While not
entirely understood, it is surmised that with this
type of training the brain is able to modify its pain
circuitry again – this time for the positive.
Gender. Even though all humans have the same
anatomical structures for the perception of pain —
nerve fibers, neurotransmitters and brain structure
— it has been found that men and women actually
process pain messages differently through their
respective circuitries. While female volunteers of pain
experiments report more severe and persistent pain
than males, women’s painkilling systems self-adjust
to greater efficiency during high-estrogen periods of
their monthly menstrual cycles. Women are also
more receptive to a class of painkillers called kappa
opioid agonists than men.
Genetics. Something so individual as having more
copies of a particular amino acid in one’s genes seems
to promote more effective painkilling mechanisms.
In scientific experiments with the gene called COMT
— which regulates the neurotransmitters dopamine
and noradrenaline — scientists found that people with
two copies of the amino acid valine on the gene were
able to endure jaw pain much better than people with
two copies of the amino acid methionine. Confirming brain scans also showed that their pain was more
efficiently modulated. With the knowledge of specific pain-related genes, it is likely that there will also
come a whole new technology of drug development
that targets only specific chemical processes in pain,
rather than a broad range of bodily processes.
Source
Pain may be classified by source as described below. Many patients with
pain will have more than one of these syndromes simultaneously, and
each syndrome responds differently to therapeutic modalities.
Nociceptive pain. Nociceptive pain can be classified in two ways:
• Somatic pain results from activation of pain receptors (nociceptors)
in the cutaneous tissue (skin), soft tissues, connective tissues, and
bone or deep tissues. This pain is typically dull or aching, but well
localized. Examples of somatic pain include metastatic bone pain,
postsurgical incisional pain and musculoskeletal pain.
• Visceral pain (deep pain) arises from noxious stimuli in the smooth
musculature or organ systems, most commonly the result of infiltration, compression, extension or stretching of these tissues. Examples
of visceral pain include that associated with myocardial infarction or
intraperitoneal metastases (cancer that has spread within the peritoneum). Visceral pain is often difficult to localize, since it is deep and
pressure-like and frequently refers to sites distant from its origin.
Neuropathic pain. This type of pain arises from injury to the peripheral or central nervous systems. It may be the result of tumor compression or infiltration of peripheral nerves of the spinal cord, or from
injury to the peripheral nerves or spinal cord as a result of trauma,
infection, surgery, radiation or chemotherapy. The most common cause
is direct nerve damage. Pain from nerve injury is often severe and is
described as burning and with a hypersensitive and/or viselike quality.
Psychogenic pain. This is an older term used to describe pain arising from a psychologic problem. Pain without organic cause is extremely
rare; it affects less than 2 percent of psychiatric patients who complain
of chronic pain and an even smaller portion of patients seen in pain clinics. Research has shown that there is a psychologic overlay to all pain
problems. Many patients with chronic pain are depressed or anxious,
and affective disorders (such as depression, anxiety and other psychiatric
April 2007 | www.pharmrep.com Pharmaceutical Representative
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Article Summary
• Between a site of active tissue damage and the perception of pain lies a complex
series of electrochemical events, collectively called nociception.
– The perception of and response to pain are widely believed to be determined by
four distinct processes: transduction, transmission, perception and modulation.
– The gate control theory is a widely accepted theory on the mechanism of pain
transmission.
• Many diverse factors influence one’s experience of pain, including continuing
noxious stimulation, gender and genetics.
• Pain classification by source includes nociceptive (somatic and visceral),
neuropathic and psychogenic pain.
• Pain may also be classified by duration (acute, chronic malignant, chronic
nonmalignant) and intensity (mild, moderate, severe, intolerable, excruciating).
• Pain assessment techniques must be tailored to the needs, abilities and
developmental level of each patient.
disorders) can exaggerate pain or cause the perception of pain when
physical damage is minimal. Thus, a distinction between physical and
psychogenic pain is somewhat artificial. Both physical and psychologic
aspects of the pain experience must be recognized and addressed.
Duration and intensity
Pain may also be classified according to the pattern of onset and duration
of the pain experience. There are three classifications:
Acute pain. Acute pain has a sudden onset, is usually self-limiting,
and generally responds to treatment with analgesic drug therapy and
to treatment of its underlying cause. Acute pain is typically associated
with hyperactivity of the autonomic nervous system (ANS) and with
three major etiologies (surgery, trauma and medical procedures).
Acute pain could last seconds, minutes, hours, days, weeks or even
months if the underlying cause is very slow to resolve. It rarely has a
strong psychogenic component.
Chronic malignant pain. Chronic malignant pain may be defined as
pain from an ongoing pathologic process or pain that continues after the
process has resolved without listing a specific time limitation. Chronic
malignant pain is associated with life-threatening diseases such as cancer, AIDS, end-stage organ disease or amyotrophic lateral sclerosis (ALS;
Lou Gehrig’s disease). Patients with chronic malignant pain may have
pain from more than one cause. For neurological reasons, a patient with
multiple sources of pain can sense only one pain at a time; if one pain
is alleviated, others may become apparent.
Chronic nonmalignant pain. Chronic nonmalignant pain is associated
with chronic diseases that are not life-threatening, such as osteoarthritis,
headaches, myofascial pain disorders and pain with no definable cause.
Aspects of the chronic pain experience often include anxiety, depression
and sleep disorder. Compared to acute pain, it often has a less sudden and
well-defined onset, and is usually accompanied by adaptation, rather than
hyperactivity, of the ANS.
Another type of pain classification considers intensity of pain, or
how strong it feels. Intensity, a subjective perception, is based on individual pain thresholds, which in turn may be subject to such factors as
physical comfort, mood, medications, psychological state and social
environment. Pain intensity is commonly characterized by words
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Pharmaceutical Representative www.pharmrep.com | April 2007
such as mild, moderate, severe, intolerable and
excruciating. With regard to pain therapy — particularly drug therapy — a distinction is commonly
made between mild to moderate pain and moderate to severe pain.
Pain assessment
Failure to properly assess pain is a critical factor
leading to its undertreatment. Pain assessment techniques must be tailored to the needs, abilities and
developmental level of each patient. Some examples
are discussed below.
Patients with cancer often have several types of
pain. It can be transient, long-term, disease-related,
treatment-related or any combination of such pains.
Because of the multiple causes of pain in these
patients, regular pain assessment should be a part of
every clinical evaluation and should occur:
• At regular intervals after initiation of treatment
or change in treatment.
• At each new report of pain.
• At suitable intervals after pharmacologic or nonpharmacologic intervention.
Initial assessment should serve to characterize
the pain by location, intensity and etiology. Essential elements of the initial assessment are a detailed
patient history, a physical examination with emphasis on the neurologic evaluation, a psychosocial
assessment, and (as needed) a diagnostic evaluation to determine the cause of new or increasing pain.
In pediatric patients, assessment strategies must
be tailored to the child’s developmental level and
personality style. Self-report tools are appropriate for
children four years and older and yield the most
accurate information. A number of self-report tools
have been developed for assessment of pain in
children. Many scales for school age children use
drawings of faces, with a smiling or neutral face representing no pain and a grimacing face representing
the worst possible pain. For preverbal/nonverbal
children, and as an adjunct to self-report with older
children, behavioral observation, physiologic measures and the parent’s report of pain should be used.
As with adult patients, pain in pediatric patients
should be assessed at regular intervals and unexpected
intense pain immediately evaluated.
For patients with osteoarthritis and rheumatoid
arthritis, pain assessment questionnaires focus
primarily on the degree to which pain restricts
normal function and activity. For example, patients
may be asked to rate severity of pain in particular
body areas at specific times of day (for example,
at night, in the morning) and pain associated with
specific activities — such as walking, dressing or
climbing stairs. Questions about “tenderness” are
widely used in assessment of rheumatoid arthritis
but are less useful in osteoarthritis.
The next article in the series will discuss pain management options.