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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 credits toward the CMR® designation. 44 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 45 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 46 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.