Porth's Essentials of Pathophysiology, 4e

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Nervous System

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through the inhibition of the cyclooxygenase (COX) enzymes, which mediate the biosynthesis of prosta- glandins. Prostaglandins (particularly prostaglandin E 2 ) exert their effect through peripheral sensitization of nociceptors to chemical mediators such as bradykinin and histamine. 27 The NSAIDs also decrease the sensitiv- ity of blood vessels to bradykinin and histamine, affect cytokine production by T lymphocytes, inhibit vasodila- tion, and decrease the release of inflammatory mediators from granulocytes and mast cells. Acetaminophen is an alternative to the NSAIDs. Although usually considered equivalent to aspirin as an analgesic and antipyretic agent, it lacks anti-inflammatory properties. Opioid Analgesics. The term opioid or narcotic is used to refer to a group of medications, natural or synthetic, with morphinelike actions. The opioids (e.g., morphine, codeine, and many other semisynthetic congeners of morphine) exert their action through opioid receptors. There are three major categories of opioid receptors in the CNS, designated as mu ( μ , for “morphine”), delta ( δ ), and kappa ( κ ). 27 Analgesia, as well as respiratory depression, miosis (constriction of the pupil), reduced gastrointestinal motility (causing constipation), feelings of well-being or euphoria, and physical dependence, principally result from morphine and morphinelike opi- oid analgesics that act at the mu receptors. Part of the pain-relieving properties of exogenous opioids such as morphine involve the release of endogenous opioids. 27 Opioids are used in the management of acute and chronic pain. When given for temporary relief of severe pain, such as that occurring after surgery, there is much evidence that opioids given routinely before the pain starts or becomes extreme are far more effective than those administered in a sporadic manner. Persons who are treated in this manner usually require fewer doses and are able to resume regular activities sooner. Opioids also are used for persons with chronic pain such as that caused by cancer. Morphine remains the most useful strong opioid, and the WHO has recommended that oral morphine be part of the essential medication list and be made available throughout the world as the med- ication of choice for cancer pain. 24,27 Adjuvant Analgesics. Adjuvant analgesics include medications such as tricyclic antidepressants, antisei- zure medications, and neuroleptic anxiolytic agents. 28 Serotonin has been shown to play an important role in producing analgesia. In recent years the use of medi- cations classified as serotonin norepinephrine reup- take inhibitors (SNRIs) have been shown to help with the treatment of chronic pain. The Food and Drug Administration (FDA) has approved two drugs in this class, duloxetine and milnacipran, for the treatment of chronic pain associated with fibromyalgia. 29 The use of these drugs has also shown potential benefit for the treatment of postherpetic neuralgia and painful diabetic neuropathy. 30 The tricyclic antidepressant medications that block the removal of serotonin from the synaptic cleft have been shown to produce pain relief in some

persons. These medications are particularly useful in some chronic painful conditions, such as postherpetic neuralgia. Antiseizure medications that suppress spon- taneous neuronal firing are particularly useful in the management of pain that occurs after nerve injury (neuropathic pain), including diabetic neuropathy and chronic regional pain syndrome. Other agents, such as the corticosteroids, may be used to decrease inflamma- tion and the nociceptive stimuli responsible for pain. Surgical Interventions If surgery removes the problem causing the pain, such as a tumor pressing on a nerve or an inflamed appendix, it can be curative. In other situations, surgery is used for symp- tom management rather than for cure. However, with rare exceptions, noninvasive analgesic approaches for pain relief should precede invasive surgical approaches. 16 Surgery for severe, intractable pain of peripheral or cen- tral origin has met with some success. It can be used to remove the cause or block the transmission of intractable pain from phantom limb pain, severe neuralgia, inoper- able cancer of certain types, and other disorders. ■■ Pain is both a protective and an unpleasant physically and emotionally disturbing sensation originating in pain receptors that respond to a number of stimuli that threaten tissue integrity. It is a symptom common to many illnesses and is a highly individualized experience that is shaped by a person’s culture and previous life experiences. ■■ Nociceptors, which are receptive nerve endings that respond to noxious or painful stimuli, transmit impulses to the dorsal horn neurons in the spinal cord using chemical neurotransmitters. ■■ There are two pathways for pain transmission: The pathway for fast, sharply discriminated pain that moves directly from the receptor to the spinal cord and from the spinal cord to the thalamus using the neospinothalamic tract; and the pathway for slow, continuously conducted pain that is transmitted to the spinal cord and from the spinal cord to the thalamus using the more circuitous and slower-conducting paleospinothalamic tract. ■■ The central processing of pain information includes transmission to the somatosensory cortex, where pain information is perceived and interpreted; the limbic system, where the emotional components of pain are experienced; and the brain stem centers, where autonomic nervous system responses are recruited. SUMMARY CONCEPTS