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Overview of Pain
Pain is the most common reason patients seek medical care. Pain has sensory and emotional components and is often classified as acute or chronic. Acute pain is frequently associated with anxiety and hyperactivity of the sympathetic nervous system (eg, tachycardia, increased respiratory rate and BP, diaphoresis, dilated pupils). Chronic pain does not involve sympathetic hyperactivity but may be associated with vegetative signs (eg, fatigue, loss of libido, loss of appetite) and depressed mood. People vary considerably in their tolerance for pain.
Acute pain, which usually occurs in response to tissue injury, results from activation of peripheral pain receptors and their specific A delta and C sensory nerve fibers (nociceptors).
Chronic pain (see Chronic Pain ) related to ongoing tissue injury is presumably caused by persistent activation of these fibers. However, the severity of tissue injury does not always predict the severity of chronic or acute pain. Chronic pain may also result from ongoing damage to or dysfunction of the peripheral or central nervous system (which causes neuropathic pain—see Neuropathic Pain ).
Nociceptive pain may be somatic or visceral. Somatic pain receptors are located in skin, subcutaneous tissues, fascia, other connective tissues, periosteum, endosteum, and joint capsules. Stimulation of these receptors usually produces sharp or dull localized pain, but burning is not uncommon if the skin or subcutaneous tissues are involved. Visceral pain receptors are located in most viscera and the surrounding connective tissue. Visceral pain due to obstruction of a hollow organ is poorly localized, deep, and cramping and may be referred to remote cutaneous sites. Visceral pain due to injury of organ capsules or other deep connective tissues may be more localized and sharp.
Psychologic factors modulate pain intensity to a highly variable degree. Thoughts and emotions have an important role in the perception of pain. Many patients who have chronic pain also have psychologic distress, especially depression and anxiety. Because certain syndromes characterized as psychiatric disorders (eg, some somatic symptom disorders—see Somatic Symptom Disorder ) are defined by self-reported pain, patients with poorly explained pain are often mischaracterized as having a psychiatric disorder and are thus deprived of appropriate care.
Pain impairs multiple cognitive domains including attention, memory, concentration, and content of thought, possibly by demanding cognitive resources.
Many pain syndromes are multifactorial. For example, chronic low back pain and most cancer pain syndromes have a prominent nociceptive component but may also involve neuropathic pain (due to nerve damage).
Pain fibers enter the spinal cord at the dorsal root ganglia and synapse in the dorsal horn. From there, fibers cross to the other side and travel up the lateral columns to the thalamus and then to the cerebral cortex.
Repetitive stimulation (eg, from a prolonged painful condition) can sensitize neurons in the dorsal horn of the spinal cord so that a lesser peripheral stimulus causes pain (wind-up phenomenon). Peripheral nerves and nerves at other levels of the CNS may also be sensitized, producing long-term synaptic changes in cortical receptive fields (remodeling) that maintain exaggerated pain perception.
Substances released when tissue is injured, including those involved in the inflammatory cascade, can sensitize peripheral nociceptors. These substances include vasoactive peptides (eg, calcitonin gene-related protein, substance P, neurokinin A) and other mediators (eg, prostaglandin E2, serotonin, bradykinin, epinephrine).
The pain signal is modulated at multiple points in both segmental and descending pathways by many neurochemical mediators, including endorphins (eg, enkephalin) and monoamines (eg, serotonin, norepinephrine ). These mediators interact in poorly understood ways to increase, sustain, shorten, or reduce the perception of and response to pain. They mediate the potential benefit of CNS-active drugs (eg, opioids, antidepressants, anticonvulsants, membrane stabilizers) that interact with specific receptors and neurochemicals in the treatment of chronic pain.
Psychologic factors are important modulators. They not only affect how patients speak about pain (eg, in a stoic, irritable, or complaining way) and how they behave in response to it (eg, whether they grimace), but they also generate neural output that modulates neurotransmission along pain pathways. Psychologic reaction to protracted pain interacts with other CNS factors to induce long-term changes in pain perception.
Risk of ulcers and GI bleeding due to NSAIDs for people > 65 is 3 to 4 times higher than that for middle-aged people. Risk depends on drug dose and duration of therapy. Elderly patients at high risk of GI adverse effects may benefit from concomitant use of cytoprotective drugs (usually, a proton pump inhibitor; occasionally, the prostaglandin misoprostol).
The newly recognized risk of cardiovascular toxicity, which presumably occurs with nonselective COX-1 and COX-2 inhibitors and with selective COX-2 inhibitors (coxibs), is particularly relevant to the elderly, who are more likely to have cardiovascular risk factors (eg, a history of MI or cerebrovascular or peripheral vascular disease).
Both nonselective and selective NSAIDs can impair renal function and cause Na and water retention; they should be used cautiously in the elderly, particularly in those who have a renal or hepatic disorder, heart failure, or hypovolemia. Rarely, NSAIDs cause cognitive impairment and personality changes in the elderly. Indomethacin causes more confusion in the elderly than other NSAIDs and should be avoided.
Given the overall greater risk of serious toxicity in the elderly, low doses of NSAIDs should be used if possible, and using short-term therapy or interrupted therapy to confirm effectiveness should be considered. NSAIDs are most likely to relieve pain generated by inflammation. Naproxen may be preferred because it appears to have a lower risk of cardiovascular adverse effects than other commonly prescribed NSAIDs.
In the elderly, opioids have a longer half-life and possibly a greater analgesic effect than in younger patients. In elderly patients with chronic pain, short-term use of opioids appears to reduce pain and improve physical functioning but to impair mental function. Opioid-related constipation and urinary retention tend to be more problematic in the elderly. Risk of fracture during the first 2 wk of treatment is higher with opioids than with NSAIDs in the elderly.
Compared with other opioids, transdermal buprenorphine, an opioid agonist/antagonist, has a more favorable risk:benefit profile in elderly patients with renal insufficiency.
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