Pain

Pain is an unpleasant, subjective experience that typically accompanies physical or psychological distress. Pain is usually described as being either nociceptive (in response to actual or potential tissue [Page 1321]damage) or neuropathic (caused by dysregulated nervous system activity).

Numerous treatments for both acute and chronic pain are available. In more severe cases, surgery may be required.

Nociceptive pain begins with nociceptors: specialized transducing elements in the tissue that convert heat, cold, and mechanical energy to electrical signals. These signals are sent to the central nervous system via two main types of nerve fibers. Thin, A-Delta fibers transmit a fast, sharp pain that causes an organism to quickly withdraw from the dangerous stimulus. A second deep and throbbing pain, mediated by C fibers, causes the organism to protect the damaged area while it heals. These nociceptive signals ascend the spinal cord and terminate in the brain where the experience of pain is generated. The pain experience itself further involves numerous brain regions associated with the sensory (thalamus and somatosensory cortex), affective (hypothalamus, medial thalamus, and limbic system), and cognitive (dorsolateral prefrontal cortex, dorsal anterior cingulate cortex) components of pain. Other brain regions, such as the periaqueductal gray and rostral ventromedial medulla, can increase or decrease the experience of pain. These structures modify nociceptive signaling in the spinal cord via descending dopaminergic, serotonergic, and norepinephrinergic pathways.

Pain may also have neuropathic origins. Neuropathic pain is caused by damage or dysregulation in the peripheral or central nervous system. The altered pain response causes a state of hyperexcitability in the neurons that relay nociceptive information. This state of hyperexcitability can result in a continuous output of pain signals, even in the absence of any observable tissue damage. Neuropathic pain is characterized by burning, shooting, and electric shock sensations.

While the control of acute pain is a major clinical concern (particularly in neonatal and perioperative pain), chronic pain is receiving increasing attention from researchers. This type of pain can last indefinitely, and has a devastating impact on social, cognitive, physical, and emotional well-being. Chronic pain may be associated with sleep difficulties, secondary fatigue, cognitive problems, depression, and anxiety. Individuals with these conditions often reduce their activities due to their fear of causing additional pain, and they risk being alienated from important social networks.

Chronic pain may be nociceptive, neuropathic, or idiopathic (of unknown origin). Chronic nociceptive pain is secondary to actual tissue damage. Examples are rheumatoid arthritis and osteoarthritis. Chronic neuropathic pain can be caused by physical trauma (phantom limb pain), viral infection (postherpetic neuralgia), and other medical conditions (diabetic neuropathy and trigeminal neuralgia). Idiopathic pain syndromes generally share characteristics of diffuse musculoskeletal pain, hypersensitivity to pain stimuli, and comorbid psychological complaints. In these disorders, no evidence for tissue damage or nervous system lesion can be found. Examples include fibromyalgia, irritable bowel syndrome, and some instances of chronic lower back pain.

Numerous treatments for both acute and chronic pain are available. Nociceptive pain may be attenuated by treating the underlying injury. For example, migraine headaches can be treated by administering vasoconstrictors. Drug therapy for acute pain includes the use of nonsteroidal antiinflammatory agents (NSAIDs) for minor pain and opioid analgesics for moderate to severe pain. These medications, however, are less effective in reducing chronic neuropathic and idiopathic pain. Many medications are prescribed off-label for the treatment of chronic pain, and can be effective for patient subgroups. Examples include anti-depressants, anticonvulsants, anxiolytics, and neurotoxins. In more severe cases of persistent and disabling pain, surgery may be required. Some procedures include spinal cord stimulators, implanted drug delivery systems, and deep brain stimulation.

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