Manegement of chronic neurogenic pain
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Manegement of chronic neurogenic pain

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  • 08/14/12 07:13 AM
  • 08/14/12 07:13 AM Numerous surveys from the United States and Europe during the last decade have shown that 30% to 50% of adult patients in active therapy for a solid tumor experienced chronic pain. With advanced disease, the prevalence of pain increased to 90%. A recent survey by the IASP concluded that the inferred mechanism of pain is neuropathic in 40% of cases. In a very large survey of institutionalized elderly patients with cancer, the prevalence of pain was 27.4%, and pain was associated independently with age, gender, race, marital status, functionality, and cognitive status. Cancer pain is often associated with psychological distress and functional impairment. Unrelieved pain may significantly impaired quality of life . In the AIDS population, the prevalence rates range from 25% to 80%. This broad range reflects differences in populations studied and pain assessment methodologies. Bernabei R, Gambassi G, Lapane K, et al: Management of pain in elderly patients with cancer. JAMA. 1998;279:1877-1882. Caraceni A, Portenoy RK, a working group of the IASP Task Force on Cancer Pain. An international survey of cancer pain characteristics and syndromes. Pain . 1999;82:263-274. Cleeland CS, Gonin R, Harfield AK, et al: Pain and its treatment in outpatients with metastatic cancer. N Engl J Med. 1994;330:592-596. Heim HM, Oei TP: Comparison of prostate cancer patients with and without pain. Pain. 1993; 53:159-162. Portenoy, RK: Cancer pain. Pathophysiology and syndromes. Lancet. 1992; 339:1026-1031. Portenoy RK, Kornblith AB, Wong G, et al: Pain in ovarian cancer. Prevalence, characteristics, and associated symptoms. Cancer . 1994;74:907-915. Serlin RC, Mendoza TR, Nakamura Y, et al: When is cancer pain mild, moderate or severe? Grading pain severity by its interference with function. Pain. 1995;61L277-284.
  • 08/14/12 07:13 AM Chronic pain may be seen as presenting a fundamental challenge to medicine. The experience of chronic pain is very common and chronic pain is part of the experience of many illnesses. However, the links between the experience of chronic pain and visible or detectable pathology or diagnosable illness are often non-existent or unclear. In philosophical terms, chronic pain challenges the distinction between mind and body which much medical knowledge assumes. It also challenges the notion of cure as a goal of medical practice. And we face such patients routinely in our practice. Infact 40% of our total patients constitute pain sufferers. And there is always an urge when talking of pain, to magnify its image, using eye-catching overstatements and graphology and create a larger than life impression. Health care professionals face pain so often; they develop some form of defense mechanism to deal with it. Some learn to ignore it, some play it down and some others dismiss it with a wry smile. But the age old adage remains and shall remain true till science evolves several steps and generations in progress; diagnose as many, treat some, cure a few, but empathize with all.
  • 08/14/12 07:13 AM Pain being such an important presenting complaint in practice, the US government declared the last decade as Decade of Pain Control and Research. This also helped in development of numerous programs to advance awareness and treatment of pain and funding for research.
  • 08/14/12 07:13 AM
  • 08/14/12 07:13 AM Neuropathic pain caused by damage to or a dysfunction of the nervous system e.g. post herpetic neuralgia, diabetic neuropathy, pain following trauma or compression is generally un-diagnosed and poorly managed Nociceptive pain is caused by noxious stimuli of pain receptors with info transferred centrally e.g inflammation or headache, it is managed by analgesics, NSAIDs or opioids
  • 08/14/12 07:13 AM Complicated by central processing that allows pain to be experienced as a cognitive function.. How we interpret pain is important and can affect patients life- as shown in next slide where the interplay of afferent and efferent fibres is demonstrated.
  • 08/14/12 07:13 AM The physiology of normal pain transmission involves some basic concepts that are necessary in order to understand the pathophysiology of abnormal or nonphysiologic pain. These include the concept of transduction of the first-order afferent neuron nociceptors. The nociceptor neurons have specific receptors that respond to specific stimuli if a specific degree of amplitude of the stimulus is applied to the receptor in the periphery. If sufficient stimulation of the receptor occurs, then there is a depolarization of the nociceptor neuron. The nociceptive axon carries this impulse from the periphery into the dorsal horn of the spinal cord to make connections directly, and indirectly, through spinal interneurons, with second-order afferent neurons in the spinal cord. The second-order neurons can transmit these impulses from the spinal cord to the brain. Second-order neurons ascend mostly via the spinothalamic tract up the spinal cord and terminate in higher neural structures, including the thalamus of the brain. Third-order neurons originate from the thalamus and transmit their signals to the cerebral cortex. Evidence exists that numerous supraspinal control areas—including the reticular formation, midbrain, thalamus, hypothalamus, the limbic system of the amygdala and the cingulate cortex, basal ganglia, and cerebral cortex—modulate pain. Neurons originating from these cerebral areas synapse with the neuronal cells of the descending spinal pathways, which terminate in the dorsal horn of the spinal cord. Brookoff D. Chronic Pain: A New Disease? Hosp Pract (Off Ed) 2000;35:45-52, 59.
  • 08/14/12 07:13 AM Expand on neural plasticity here – changes in chronic pain vs acute pain is important
  • 08/14/12 07:13 AM Chronic pain is not just a prolonged version of acute pain. It often occurs in the absence of ongoing illness or after healing is completed, and often begins with an injury that causes inflammation and CNS changes. The injured area heals, scar tissue is formed, and the inflammation recedes. But for an unknown reason, the nervous system undergoes multiple changes that perpetuate the pain experience, continuing to send pain signals to somatic muscles. The nervous system reacts to the memory of the original injury and sends signals like those sent in response to that original injury. These signals become a recurring and disabling message that remind the patient of the original injury. As pain signals are repeatedly generated, neural pathways undergo physiochemical changes that make them hypersensitive to the pain signals and resistant to antinociceptive input. The pain signals can become embedded in the spinal cord, like a painful memory. This is why the c urrent perception of pain can be influenced by prior experience of chronic pain. Marcus D. Treatment of nonmalignant chronic pain. Am Fam Physician. 2000;61:1331-1338; 1345-1346.
  • 08/14/12 07:13 AM Pain signals in the form of electrical impulses are carried by peripheral nerves called nociceptors (C-fibers) that synapse with neurons in the dorsal horn of the spinal cord. The pain signal is then transmitted via the spinothalamic tract to the cerebral cortex, where it is perceived, localized, and interpreted. The body’s pain-relieving, or antinociceptive, system balances out the pain-sensing system. When pain signals transmitted by peripheral nerves, or nociceptors , arrive in the brain, they activate neurons in the periaqueductal gray matter of the brain and the nucleus raphe magnus of the brainstem, which release endorphins and enkephalins. In addition to pain signals, other stimuli can trigger activation of the anti-nociceptive system, such as exercise, meditation, and comforting or reassurance. This explains the utility of many of the behavioral components of pain management programs. Image adapted with permission: Brookoff D. Chronic Pain: A New Disease? Hosp Pract (Off Ed) 2000;35(7): 45-52, 59. ©The McGraw-Hill Companies, Inc. Illustration by Seward Hung. Besson, JM. The neurobiology of pain. Lancet. 1999;353:1610- 1615 .
  • 08/14/12 07:13 AM Effective management of pain relies on a comprehensive assessment that defines the characteristics, etiology, and the underlying pathophysiology of the pain. Etiology. Defining the underlying organic activity that may be contributing to the pain may clarify the nature of the disease, indicate a prognosis, or suggest the use of specific therapies. Pathophysiology. Animal and clinical research suggest that the clinical presentation and the response to therapy of a particular pain syndrome may be determined by factors linked to the underlying mechanism of the pain. Although the classification that can be derived from such observations may be oversimplistic, it has clinical utility and so has become widely accepted. Using this scheme, the predominating pathophysiology of pain can be broadly defined as nociceptive, neuropathic, and idiopathic. Characteristics. The patient should be asked to describe the characteristics of the pain in terms of temporal aspects, intensity, topography, and exacerbating/relieving factors. Portenoy RK, Kanner RM, eds. Pain Management: Theory and Practice. Philadelphia, PA: FA Davis Company; 1996:11.
  • 08/14/12 07:13 AM Nociceptive pain is presumably related to ongoing activation of primary afferent neurons responsive to noxious stimuli. The activation of the nociceptors is related to tissue damage, although the relationship between pain and tissue damage is neither uniform nor constant. Nociceptive pain includes somatic pain and visceral pain. Somatic pain refers to ongoing activation of somatic afferent neurons. Bone pain is a typical example of this type of pain. Visceral pain is related to the activation of the primary afferent neurons that innervate viscera. Liver capsular pain is an example of visceral pain. Loeser JDF, Butler SH, Chapman CR et al. Bonica’s Management of Pain. 3 rd ed. Baltimore: Lippincott Williams Wilkins; 2001:581. Portenoy RK, Kanner RM, eds. Pain Management: Theory and Practice. Philadelphia, PA: FA Davis Company; 1996:11. Loeser JDF, Butler, SH, Chapman CR et al. Bonica’s Management of Pain, 3 rd Ed., Baltimore, Lippincott Williams Wilkins , 2001. Portenoy RK, Kanner RM, eds. Pain Management: Theory and Practice. Philadelphia, PA: FA Davis Company; 1996:219-247.
  • 08/14/12 07:13 AM Neuropathic pain is believed to be sustained by aberrant somatosensory processing in the peripheral or central nervous system. It includes numerous clinical entities, which vary in their presentation pathophysiology and treatment. The classification is based on inferred location of the pain “generator” (peripheral or central) and types of mechanisms involved. Three major categories have been recognized: deafferentation pain, sympathetically-maintained pain and peripheral neuropathic pain. Deafferentation pains are presumably related to pathophysiologic processes in the CNS. Subtypes include pain caused by injury to the brain or spinal cord, phantom pain, postherpetic neuralgia and pain caused by root avulsion. Sympathetically-maintained pain is defined as a pain presumed to be sustained by efferent activity in the sympathetic nervous system. A sympathetic nerve block is needed to establish the diagnosis of sympathetically-maintained pain. This type of pain appears to occur most frequently in the setting of a complex regional pain syndrome. The term complex regional pain syndrome (CRPS), also known as reflex sympathetic dystrophy or causalgia , refers to a regional pain syndrome in which pain is associated with focal autonomic dysfunction (vasomotor instability, swelling, sweating) and/or trophic changes (thinning of the skin, changes in hair growth, bone and subcutaneous tissue losses). Peripheral neuropathic pain is usually caused by a focal peripheral nerve injury or by a diffuse injury (polyneuropathy). Portenoy RK, Kanner RM, eds. Pain Management: Theory and Practice. Philadelphia, PA: FA Davis Company; 1996:83, 87, 93.
  • 08/14/12 07:13 AM Idiopathic pain persists in the absence of an identifiable organic substrate and is believed to be excessive for the organic processes that exist. This type of pain is uncommon in mentally ill patients. A subgroup of patients with idiopathic pain presents positive evidence of a predominant psychologic contribution to the pain. These pains are described as psychogenic or are labeled with a specific psychiatric diagnosis. Loeser JDF, Butler SH, Chapman CR et al. Bonica’s Management of Pain. 3 rd ed. Baltimore: Lippincott Williams Wilkins; 2001:19-21. Merskey H, Bogduk N, eds. Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Chronic Pain Syndromes and Definitions of Pain Terms . 2nd ed. Seattle, WA: IASP Press; 1994. Portenoy RK, Kanner RM, eds. Pain Management: Theory and Practice. Philadelphia, PA: FA Davis Company; 1996:11.
  • 08/14/12 07:13 AM Since the early 1960’s, developments have taken place that can rectify some of the deficiencies in the understanding and treatment of pain that existed even in the early 20 th century. Research has given us a greater understanding of the pathophysiology underlying many chronic pain syndromes. This understanding has led to advances in drug therapies, the use of multimodal therapies, and the belief that in some cases the optimal treatment of chronic pain is best managed by a multidisciplinary team. A pioneer and giant in the field of pain therapy, J ohn Bonica, established the first multidisciplinary pain clinic, the Multidisciplinary Pain Center, at the University of Washington in 1960. Patient’s rights movements have been supported by documents such as the Joint Commission on Accreditation of Healthcare Association’s (JCAHO) Pain Standards for 2001 , which states that all patients have the right to the appropriate assessment and management of pain. Joint Commission on the Accreditation of Healthcare Organizations. Patient Rights and Organization Ethics. Referenced from the Comprehensive Accreditation Manual for Hospitals, Update 3, 1999. http://www.jcaho.org/standards_frm.html Loeser JDF, Butler SH, Chapman CR et al. Bonica’s Management of Pain. 3 rd ed. Baltimore: Lippincott Williams Wilkins; 2001:3-15.
  • 08/14/12 07:13 AM Numerous surveys from the United States and Europe during the last decade have shown that 30% to 50% of adult patients in active therapy for a solid tumor experienced chronic pain. With advanced disease, the prevalence of pain increased to 90%. A recent survey by the IASP concluded that the inferred mechanism of pain is neuropathic in 40% of cases. In a very large survey of institutionalized elderly patients with cancer, the prevalence of pain was 27.4%, and pain was associated independently with age, gender, race, marital status, functionality, and cognitive status. Cancer pain is often associated with psychological distress and functional impairment. Unrelieved pain may significantly impaired quality of life . In the AIDS population, the prevalence rates range from 25% to 80%. This broad range reflects differences in populations studied and pain assessment methodologies. Bernabei R, Gambassi G, Lapane K, et al: Management of pain in elderly patients with cancer. JAMA. 1998;279:1877-1882. Caraceni A, Portenoy RK, a working group of the IASP Task Force on Cancer Pain. An international survey of cancer pain characteristics and syndromes. Pain . 1999;82:263-274. Cleeland CS, Gonin R, Harfield AK, et al: Pain and its treatment in outpatients with metastatic cancer. N Engl J Med. 1994;330:592-596. Heim HM, Oei TP: Comparison of prostate cancer patients with and without pain. Pain. 1993; 53:159-162. Portenoy, RK: Cancer pain. Pathophysiology and syndromes. Lancet. 1992; 339:1026-1031. Portenoy RK, Kornblith AB, Wong G, et al: Pain in ovarian cancer. Prevalence, characteristics, and associated symptoms. Cancer . 1994;74:907-915. Serlin RC, Mendoza TR, Nakamura Y, et al: When is cancer pain mild, moderate or severe? Grading pain severity by its interference with function. Pain. 1995;61L277-284.
  • 08/14/12 07:13 AM The goal of pain assessment is the development of a pain-oriented problem list, which, in addition to characterizing pain, prioritizes other physical and psychosocial problems that may influence therapy or be amenable to primary treatment. Portenoy RK, Payne R: Acute and chronic pain. In: Lowinson JH, Ruiz P, Millman RB, eds. Comprehensive Textbook of Substance Abuse. 3rd ed. Baltimore, MD: Williams & Wilkins; 1997:563-589.
  • 08/14/12 07:13 AM In order to make a comprehensive evaluation, the physician must take a detailed history from the patient. Temporal Features. Temporal features include onset, duration, frequency and constancy of the pain. Pain can be acute or chronic. Chronic pain may be punctuated by breakthrough pains (transitory acute pain). Intensity. Pain intensity should be measured validly and repeatedly using a simple scale. (See next slide) Topography. Pain can be described as focal, multifocal, generalized, referred. Focal pain s are usually well circumscribed, at the site of the lesion. Referred pains are experienced at a site remote from the presumed lesion. Pains can be referred from an injury in any deep tissues, including viscera, muscle, bone and peripheral or central nervous system. Quality. Descriptors of pain quality can be clues to underlying mechanisms. Somatic pains are often described as aching, throbbing or sometimes stabbing. The quality of visceral pains will vary according to the organ. In injury to hollow viscus, the pain is often described as cramping or gnawing. Neuropathic pains are usually described as dysesthesic (lancinating, burning, electric-shock-like, tingling). Exacerbating/Relieving Factors. Factors that aggravate or relieve pain may be useful for diagnostic purposes and treatment: they can be categorized as volitional or spontaneous. Pain induced by light touch on normal skin (allodynia) suggests a neuropathic component. Portenoy RK, Payne R: Acute and chronic pain. In: Lowinson JH, Ruiz P, Millman RB, eds. Comprehensive Textbook of Substance Abuse, 3rd ed. Baltimore, MD: Williams & Wilkins; 1997:566-567.
  • 08/14/12 07:13 AM A “faces” scale may be useful for patients who are unable to use NRS or VAS scales, such as children, the elderly, or patients with dementia. The Brief Pain Inventory is a straightforward and easily administered tool that provides the practitioner with information about pain history, intensity, location, quality, and interference. It includes a number of questions, each of which is answered by the patient on a scale of 1 to 10. Included are questions about pain characteristics as well as functionality. It also includes the simple body outlines above, on which the patient is asked to mark the areas of greatest pain. Cleeland, CS. Pain Research Group University of Texas M.D.Anderson Cancer Center. BPI Copyright 1991. Wong DL, Hockenberry-Eaton M, Wilson D, Winkelstein ML, Schwartz P. Wong’s Essentials of Pediatric Nursing. 6 th ed. St Louis, Missouri: Mosby, Inc.; 2001:1301. Reprinted by permission .
  • 08/14/12 07:13 AM
  • 08/14/12 07:13 AM Opioid Analgesics . Opioids are the mainstay drugs for moderate-to-severe pain associated with medical illness. Opioid analgesics can be classified as pure mu-agonists or agonist-antagonists based on their receptor interactions. The agonist-antagonist class can be subdivided into a mixed agonist-antagonist subclass and a partial agonist subclass. Because of their ceiling effect for analgesia and potential for reversing analgesia from pure agonists in physically-dependent patients, the agonist-antagonist drugs are not preferred for treating chronic pain. Nonopioid Analgesics. N onopioid analgesics include acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDS). They are usually used for mild-to-moderate pain. They have an additive effect when combined with opioids. There is substantial variability in the response of individual patients to different drugs. The selective COX-2 inhibitors (celecoxib, rofecoxib, valdecoxib, oncloxicam) have a more favorable GI safety profile than the nonselective COX-1 and COX-2 inhibitors. The nonselective drugs vary in toxicity. Drug selection should be influenced by drug-selective toxicities, prior experience, cost, and convenience. Adjuvant Analgesics. Adjuvant analgesics are drugs that have other primary indications but may be analgesic in specific circumstances. In the medically ill, adjuvant analgesics are more commonly used in the treatment of neuropathic pain. Drug selection should be guided by the risks associated with the therapy and the possibility of secondary benefits for symptoms other than pain. Sequential trials and dose titration are usually necessary. The appropriate use of adjuvant analgesics requires the clinician to know the approved indications, side effects, time-action relationship, pharmacokinetics, and specific guidelines for use in pain treatment. Cashman JN. The mechanisms of action of NSAIDS in analgesia. Drugs. 1996;52(suppl 5):S13-S23 . Galer BS. Painful poplyneuropathy. Neurologic Clinics. 1998;16(4):791-811. Hanks GW, Portenoy RK, MacDonald N, et al. Difficult pain problems. In: Doyle D, Hanks GW, MacDonald N, eds. Oxford Textbook of Palliative Medicine . Oxford: Oxford University Press; 1998:454. Langman MJ, Jensen DM, Watson DJ, et al. Adverse upper gastrointestinal effects of rofecoxib compared with NSAIDs. JAMA. 1999;282:1929-1933. Simon LS, Weaver AL, Graham DY, et al. Anti-inflammatory and upper gastrointestinal effects of celocoxib in rheumatoid arthritis: a randomized controlled trial. JAMA. 1999;282:1921-1928.   Stein C. The control of pain in peripheral tissues by opioids. N Engl J Med. 1995;332:1685-1690.
  • 08/14/12 07:13 AM His first task as Head at the Institute was to develop new antihistamines, which would complement promethazine and diphenhydramine developed by Rhone-Poulenc in France and Parke-Davis in the United States, respectively. Let me remind you that this was the Czechoslovakia of a communistic regime and hence the value to the contribution is a bit toned down in literature. However the discovery was significant.
  • 08/14/12 07:13 AM
  • 08/14/12 07:13 AM The physiology of normal pain transmission involves some basic concepts that are necessary in order to understand the pathophysiology of abnormal or nonphysiologic pain. These include the concept of transduction of the first-order afferent neuron nociceptors. The nociceptor neurons have specific receptors that respond to specific stimuli if a specific degree of amplitude of the stimulus is applied to the receptor in the periphery. If sufficient stimulation of the receptor occurs, then there is a depolarization of the nociceptor neuron. The nociceptive axon carries this impulse from the periphery into the dorsal horn of the spinal cord to make connections directly, and indirectly, through spinal interneurons, with second-order afferent neurons in the spinal cord. The second-order neurons can transmit these impulses from the spinal cord to the brain. Second-order neurons ascend mostly via the spinothalamic tract up the spinal cord and terminate in higher neural structures, including the thalamus of the brain. Third-order neurons originate from the thalamus and transmit their signals to the cerebral cortex. Evidence exists that numerous supraspinal control areas—including the reticular formation, midbrain, thalamus, hypothalamus, the limbic system of the amygdala and the cingulate cortex, basal ganglia, and cerebral cortex—modulate pain. Neurons originating from these cerebral areas synapse with the neuronal cells of the descending spinal pathways, which terminate in the dorsal horn of the spinal cord. Brookoff D. Chronic Pain: A New Disease? Hosp Pract (Off Ed) 2000;35:45-52, 59.
  • 08/14/12 07:13 AM

Manegement of chronic neurogenic pain Manegement of chronic neurogenic pain Presentation Transcript

  • MANEGEMENT OF CHRONIC(NEUROGENIC) PAIN Dr. A.V. Srinivasan MD.,DM.,Ph.D ., D.Sc (HON).F.I.A.N.,F.A.AN. Emeritus professor of Tamilnadu Dr. M.G.R Medical University. Adjunct Professor –IIT, Chennai Former Head, Institute of Neurology- Madras medical college. South Africa -26-07-2011
  • Chronic Pain Understanding, Impact and AwarenessProthiaden in Chronic Pain Company Confidential © 2010 Abbott
  • “Pain May be Inevitable, but Misery is Optional” Dee Malchow Pain constitutes nearly 40% of the total of patient visits to doctors.1 1 Mäntyselkä et al. Pain as a reason to visit the doctor: a study in Finnish primary health care. Pain. 2001 Jan;89(2-3):175-80.Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Pain is undertreated • In 2001, Barry Furrow wrote “Pain is undertreated” in the American health- care system at all levels.2 • The term "opiophobia" has been coined to describe this remarkable clinical aversion to the proper use of opioids to control pain. • The possible reasons for health-care providers failures to properly manage pain are many; – Occasional lack of knowledge about appropriate treatment choices for pain management – A reflection of a Culture hostile to drug use – Threats of legal action. – Worry about tolerance and addiction and other adverse drug effects – Something as trivial as the lack of insurance cover, can lead to patients suffering unnecessary pain as a result. 2. R.M. Marks and E.J. Sachar, "Undertreatment of Medical Inpatients with Narcotic Analgesics,"Annals of Internal Medicine, 78 (1973): 173.Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Indian Scenario • Despite an essentially stoic and less demanding Indian patient; the obligation to manage pain comes to the fore not only to complete the perfection of a clinicians management. • But also, it is an independent entity with physical and psychological components that in adherence to best practices can neither be ignored nor treated such that adverse effects eclipse the malady. • This importance of pain management is further increased when benefits for the patient are realized, – Early mobilization which tends to prevent the more dangerous complication of a deep vein thrombosis; – Shortening hospital stay – Reducing costsProthiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Decade of Pain Control and Research • In late 2000, US Congress passed into law a provision, which the president signed , that declared the 10 year period beginning Jan 1st 2001, as the Decade of Pain Control and Research. • The American Pain Society has actively supported the Decade of Pain Control Research, and it has been a focal point for the development of numerous programs to advance awareness and treatment of pain and funding for research.Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • What is Pain? • Pain is always a subjective experience • Everyone learns the meaning of “pain” through experiences usually related to injuries in early life • As an unpleasant sensation it becomes an emotional experience • Pain is a significant stress physically, emotionally The International Association for the Safety of Pain (IASP) defines pain an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage, or both. (American Society of Anesthesiologists, 2002; Loeser et al, 2001; Merskey H et al, 1994; Portenoy et al, 1996)Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Qualities of Pain • Organic vs. psychogenic • Acute vs. chronic • Malignant or benign • Continuous or episodic Perceiving Pain • Algogenic substances – chemicals released at the site of the injury • Nociceptors – afferent neurons that carry pain messages • Referred pain – pain that is perceived as if it were coming from somewhere else in the bodyProthiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Acute vs. Chronic Pain ACUTE CHRONIC Function To warn None (destructive) Etiology Usually Clear Complex/obscure Pt. Mood Anxiety/fear Depression/anger MD impact Comforting Frustrating/draining Role of Rx Control/cure Improve function/QOLProthiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Categorization of Chronic pain Types of Pain Types of Pain (Psychogenic) (Psychogenic) Pain arising from Pain arising from Pain arising from Pain arising from pain receptors pain receptors Pain with NO apparent cause Pain with NO apparent cause Nervous system Nervous system [Nociceptive Pain] [Nociceptive Pain] (e.g. Low back pain or some (e.g. Low back pain or some [Neuropathic Pain] [Neuropathic Pain] pelvic pain in women) pelvic pain in women) Peripheral Peripheral Central CentralSuperficical / /SomaticSuperficical Somatic Deep / /Visceral Deep Visceral (Brain and Spinal cord) (Peripheral nervous (Peripheral nervous (Brain and Spinal cord) system) system)Keay, KA; Clement, CI; Bandler, R (2000). "The neuroanatomy of cardiac nociceptive pathways". in Horst, GJT. The nervous system and the heart.Totowa, New Jersey: Humana Press. p. 304Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Different types of pain Nociceptive descriptors Neuropathic descriptors Cramping, tender Shooting Gnawing, heavy Hot-burning Aching Sharp Splitting StabbingProthiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Current Understanding of Pain • Chronic pain is NOT a normal part of aging. • Emotions play a key role in painful experience • Pain sounds a warning, signaling damage to tissues, and has survival value so pain receptors do not adapt to prolonged stimulation and pain sensation may intensify as pain thresholds are lowered by continued stimulation. • The 19th Century viewed pain as a solely physiological entity with two theories dominating – the “specificity” & the “summation” theories. 8 • Paradigm Shift: – Pain perception impulses are modified by ascending and by descending pain-suppressing systems activated by various environmental and psychological factors. – 1965 Melzack & Wall: Gate Theory of Pain marked a turning point in understanding transmission and modulation of nociceptive signals, and recognition of pain as a psychophysiological phenomenon. • The concept of Neuroplasticity was recognized and accepted adding dynamism to neuronal & brain structure with neuroimaging of the central nervous system in three domains; anatomical, functional, and chemical imaging helping measure changes in chronic pain. • Taken together these three domains have changed our thinking on pain; now considered an altered brain state in which there may be altered functional connections or systems and components of degenerative aspects of the CNS. 98) 11. J.A. Paice, C. Toy, and S. Short, "Barriers to Cancer Pain Relief: Fear of Tolerance and Addiction," Journal of Pain and Symptom Management, 16 July 1998): 1-9.9) Quick Reference Guide for Clinicians No. 1a. AHCPR Publication No. 92-0019: February 1993Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Understanding Pain PathophysiologyProthiaden in Chronic Pain Company Confidential © 2010 Abbott
  • What causes pain? • Trauma/ injury initiates immediate nerve impulses to brain • Injury to cells result in chemical release • H+ • K+ • Substance P • Bradykinin • 5HT • Phospholipids ⇒Prostaglandins • Blood vessels leak resulting in inflammation • Stimulate C-fibres (slow response)Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Peripheral and Central Pathways for Pain Ascending Tracts Descending Tracts Cortex Thalamus Midbrain Pons Medulla(Brookoff, 2000) Spinal Cord Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Pain PathwayProthiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Pathophysiology of Chronic Pain • In chronic pain, the nervous system remodels continuously in response to repeated pain signals – nerves become hypersensitive to pain – nerves become resistant to anti-nociceptive system • If untreated, pain signals will continue even after injury resolves • Chronic pain signals become embedded in the central nervous system (Marcus, 2000)Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Pain-Sensing System in the Malfunction in Chronic Pain Acute pain: Pain Pain-sensing signals are initiated in response to a Sensing stimulus • They elicit a pain-In chronic pain, relieving responsepain signals aregeneratedwithout Chronic pain:physiologicsignificance Pain signals are generated for no reason and may be intensified • Pain-relieving mechanisms may be defective or deactivated (Illustration: Seward Hung, 2000)Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Pathophysiology of Pain • Inferred from characteristics, etiology or pathophysiology • Types – Nociceptive – Neuropathic – Idiopathic • Therapeutic implicationsProthiaden in Chronic Pain et (Portenoy al, 1996) Company Confidential © 2010 Abbott
  • Nociceptive Pain Presumably results from ongoing activation of primary afferent neurons responding to noxious stimuli • Pain consistent with degree of tissue injury • Described as aching, squeezing, stabbing, throbbing • Subtypes: – Somatic: related to activation of somatic afferent neurons – Visceral: related to activation of visceral afferent neurons (Loeser et al, 2001; Portenoy et al, 1996)Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Neuropathic Pain• Initiated by a primary lesion in the nervous system; believed to be sustained by aberrant somatosensory processing in the peripheral or central nervous system• Independent of obvious ongoing nociceptive activation• Burning, shooting, electrical quality; may be aching, throbbing, sharp• Subtypes: – Presumed “central generator”  deafferentation pain (central pain, phantom pain)  Sympathetically-maintained pain – Presumed “peripheral generator”  Polyneuropathies and mononeuropathies (Portenoy et al, 1996)Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Idiopathic and Psychogenic Pain Idiopathic Pain • Usually exists in the absence of an identifiable physical or psychologic pathology that could account for pain • Uncommon in patients with progressive illness Psychogenic Pain • Presents positive evidence of a predominant psychologic contribution and may be labeled with a specific psychiatric diagnosis (Loeser et al, 2001; Merskey et al, 1994; Portenoy et al, 1996)Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Recent Developments In Pain Management • Greater understanding of the pathophysiology underlying chronic pain syndromes • Scientific breakthroughs in molecular biology; insight into pain at the molecular level • Advances in drug therapy (drug delivery technologies) • Multimodal therapy • Multidisciplinary teams, shared decision-making that includes patients • Patients’ rights movement (JCAHO, 1999; Loeser et al, 2001)Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Progress in Chronic Pain Management: Therapeutic Modalities for Chronic Pain Management AssessmentProthiaden in Chronic Pain Company Confidential © 2010 Abbott
  • “Describing pain only in terms of its intensity is like describing music only in terms of its loudness” von Baeyer CL; Pain Research and Management 11(3) 2006; p.157-162Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Pain Assessment • Characterize the pain • Characterize the disease, relationship between pain and disease and potentially treatable etiologies • Clarify syndromes and infer pathophysiology • Determine need for urgent therapy • Identify other needs • Develop a therapeutic strategy (Portenoy et al, 1997)Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Pain Assessment Components • History: temporal features, intensity, topography, quality, exacerbating/alleviating factors • Physical Exam: determine existence of underlying pathology • Lab and Radiographic Tests: appropriate to pain syndrome Assessment Tools • Pain Intensity Scales: VAS, NAS, “faces” scale • Multidimensional Pain Measures: Brief Pain Inventory, McGill Pain Questionnaire (Portenoy et al, 1997)Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Pain Intensity Rating Scales • Visual Analogue Scale (VAS) No pain ----------------------------------- Worst pain • Numerical Rating Scale 0 ------------------------------------- 10 Worst pain No pain imaginable • Categorical Scale None (0) Mild (1 – 4) Moderate (5 – 6) Severe (7 – 10) • Pain Faces Scale 0 2 4 6 8 10 No Hurts just a Hurts a little Hurts even Hurts a whole Hurts as much hurt little bit bit more more lot as you can imagine • Brief Pain Inventory Shade areas of worst pain. Put an X on area that hurts most (Cleeland, 1991; Jacox et al, 1994)Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Progress in Chronic Pain Management Therapeutic Modalities for Chronic Pain Management: TreatmentProthiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Therapeutic Options for Chronic Pain Management • Pharmacotherapy (Analgesics) – Non-opioids – Adjuvant Analgesics • Antidepressants • Anticonvulsants – Opioids • Rehabilitative Approaches • Psychologic Interventions • Anesthesiological Approaches • Neurostimulatory Techniques • Surgery • Complementary/Alternative Approaches • Lifestyle Changes (Cashman, 1996; Portenoy et al, 1997; Hanks et al, 1998; Galer, 1998; Stein, 1995)Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Status of antidepressants in chronic pain management • Best evidence: TCAs – Inhibit both NA and 5-HT reuptake • TCAs are superior to SSRIs in pain management • TCAs are superior to the anticonvulsant • There is no consensus regarding which of the many TCA derivatives is most effective. • The choice of TCA is therefore dictated largely by adverse effects Neurologic Complications of Cancer Therapy Current Treatment Options in Neurology 1999, 1.428-437 Litsedge, A Double-Blind Comparison of Dothiepin and Amitriptyline for the Treatment of Depression with Anxiety, Psychopharmacologia (Berl.) 19, 153--162 (1971)Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Which TCA? • TCAs differ little in terms of their analgesic efficacy (Dworkin et. al 2007). • Amitriptyline is the most widely studied TCA and is commonly used in neuropathic pain. • Prothiaden being similar to amitriptyline is a good choice for the management of pain especially as it enjoys a relatively safer adverse event profile. Prothiaden is a derivative of amitriptyline namely its thio-analogue. Amitriptyline ProthaidenProthiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Prothiaden: Pharmacokinetics – Rapidly absorbed from GIT on oral administration – Tmax: 3 - 4 hours – Metabolized in liver to active metabolites - northiaden, northiaden S-oxide and dothiepin S-oxide – Excreted mainly in urine and also in faeces – A half-life of about 50 hours has been reported for dosulepin and its metabolitesProthiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Safety Adverse events: – Atropine-like side effects including dry mouth, disturbance of accommodation, tachycardia, constipation and hesitancy of micturition, are common early in treatment, but usually lessen as treatment continues – Initially, dosulepin may impair alertness; patients likely to drive vehicles or operate machinery should be warned of this possibility. Contra-indications : Recent MI, heart block, arrhythmias, mania, liver disease & during breast feeding Dose: Adults: 50 mg to 150 mg daily. Children: Not studied Pregnancy and lactation: Not adequately studiedProthiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Tolerability • Extensive clinical studies as well as over two decades of clinical experience indicate that it is a well tolerated drug. • The nature of side-effects reported are typical of a tricyclic antidepressant, it is better tolerated than other tricyclic antidepressants. • “The general trend appeared to show better patient tolerance of Dothiepin than to any other active controls”. • Goldstein and Claghorn (1980) Dothiepin is better tolerated in relation to its side effects than amitriptyline. Litsedge, A Double-Blind Comparison of Dothiepin and Amitriptyline for the Treatment of Depression with Anxiety, Psychopharmacologia (Berl.) 19, 153--162 (1971)Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Mode of action: Dosulepin in chronic pain Dosulepin potentiate serotonin and norepinephrine in descending pain-suppression pathways in the spinal cord. Descending fibers that pass down from brainstem to spinal cord, inhibiting incoming sensations (ascending pathways) of pain. A lot of these descending fibers originate in the locus ceruleus, others in the raphe nuclei. Jann et. al. Antidepressant Agents for the Treatment of Chronic Pain and Depression. Pharmacotherapy 2007;27(11):1571–1587 Daniel a. Monti M.D. et. al. Management of chronic pain in elderly patients. Practical geriatrics; December 1996 Vol 49, No. 12 Brookoff, 2000Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Mode of action Ascending Tracts Descending Tracts TCAs potentiate serotonin and norepinephrine in descending pain- suppression pathways in the spinal cord. Descending fibres that pass down from brainstem to spinal cord, inhibiting incoming sensations (ascending pathways) of pain. A lot of these descending fibres originate in the locus coeruleus, others in the raphe nuclei. Prothiaden in Chronic Pain Company Confidential © 2010 Abbott(Brookoff, 2000)
  • Dothiepin in management of chronic pain • Dothiepin was used in a titrating dose in patients of atypical facial pain (Starting dose 12.5 mg, dose range 25-137.5 mglday) for 9weeks – 34/48 dothiepin were pain free (score 0/1 mild, occasional) at week 9. vs 21/45 placebo – Reduction in analgesic use; 83% dothiepin, 42% placebo (Feinmannet al.,1984)Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Proven efficacy in managing chronic pain – In Prothiaden group pain score measured on VAS reduced from 56.7 to 42.2 – In placebo group, pain score increased from 59.7 to 64.1 – Dothiepin is effective in relieving pain, disability and reducing the duration of early morning stiffness in out- patients with RA – The analgesic effect of dosulepin is INDEPENDENT of its antidepressant effect G. Ash et. al. The effect of dothiepin on subjects with rheumatoid arthritis and depression. Rheumatology 1999; 38: 959-967Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Recommendations of Treatment GuidelinesProthiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Practice Guidelines for Chronic Pain Management • Developed by American Society of Anesthesiologists Task Force on Chronic Pain Management and the American Society of Regional Anesthesia and Pain Medicine • Meta-analyses of randomized controlled trials indicate that tricyclic antidepressants provide effective pain relief for a variety of chronic pain etiologies for assessment periods ranging from 2 to 8 weeks, with dry mouth and somnolence or sedation as reported side effects (Category A1 evidence). • Strongly agree to use of TCAs in chronic pain management. Anesthesiology 2010; 112:810 –33Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Prothiaden in Chronic Pain Company Confidential © 2010 Abbott
  • Take Homes ! Pain needs to be treated TCAs are the aggressively to recommended first-line prevent sensitization therapy in chronic pain Dothiepin is better Chronic pain even more tolerated in relation so as to combat to its side effects Neuroplasticity than amitriptylineProthiaden in Chronic Pain Company Confidential © 2010 Abbott
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  • READ NOT TO CONTRADICT OR CONFUTE NOR TO BELIEVE AND TAKE FOR GRANTED BUT TO WEIGH AND CONSIDER THANKYOU My sincere thanks to ABBOTT and SAMPATH(CRO)Prothiaden in Chronic Pain Company Confidential © 2010 Abbott