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Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain's widely used definition defines pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage"; however, due to it being a complex, subjective phenomenon, defining pain has been a challenge. In medical diagnosis, pain is regarded as a symptom of an underlying condition.

Neuropathic pain is caused by damage or disease affecting any part of the nervous system involved in bodily feelings (the somatosensory system). Neuropathic pain may be divided into peripheral, central, or mixed (peripheral and central) neuropathic pain. Peripheral neuropathic pain is often described as "burning", "tingling", "electrical", "stabbing", or "pins and needles". Bumping the "funny bone" elicits acute peripheral neuropathic pain.

Local anesthetic injections into the nerves or sensitive areas of the stump may relieve pain for days, weeks, or sometimes permanently, despite the drug wearing off in a matter of hours; and small injections of hypertonic saline into the soft tissue between vertebrae produces local pain that radiates into the phantom limb for ten minutes or so and may be followed by hours, weeks or even longer of partial or total relief from phantom pain. Vigorous vibration or electrical stimulation of the stump, or current from electrodes surgically implanted onto the spinal cord, all produce relief in some patients.

Breakthrough pain is transitory pain that comes on suddenly and is not alleviated by the patient's regular pain management. It is common in cancer patients who often have background pain that is generally well-controlled by medications, but who also sometimes experience bouts of severe pain that from time to time "breaks through" the medication. The characteristics of breakthrough cancer pain vary from person to person and according to the cause. Management of breakthrough pain can entail intensive use of opioids, including fentanyl.

Although pain is considered to be aversive and unpleasant and is therefore usually avoided, a meta-analysis which summarized and evaluated numerous studies from various psychological disciplines, found a reduction in negative affect. Across studies, participants that were subjected to acute physical pain in the laboratory subsequently reported feeling better than those in non-painful control conditions, a finding which was also reflected in physiological parameters. A potential mechanism to explain this effect is provided by the opponent-process theory.

Wilhelm Erb's (1874) "intensive" theory, that a pain signal can be generated by intense enough stimulation of any sensory receptor, has been soundly disproved. Some sensory fibers do not differentiate between noxious and non-noxious stimuli, while others, nociceptors, respond only to noxious, high intensity stimuli. At the peripheral end of the nociceptor, noxious stimuli generate currents that, above a given threshold, send signals along the nerve fiber to the spinal cord. The "specificity" (whether it responds to thermal, chemical or mechanical features of its environment) of a nociceptor is determined by which ion channels it expresses at its peripheral end. Dozens of different types of nociceptor ion channels have so far been identified, and their exact functions are still being determined.

Cultural barriers may also affect the likelihood of reporting pain. Sufferers may feel that certain treatments go against their religious beliefs. They may not report pain because they feel it is a sign that death is near. Many people fear the stigma of addiction, and avoid pain treatment so as not to be prescribed potentially addicting drugs. Many Asians do not want to lose respect in society by admitting they are in pain and need help, believing the pain should be borne in silence, while other cultures feel they should report pain immediately to receive immediate relief. Gender can also be a factor in reporting pain. Gender differences can be the result of social and cultural expectations, with women expected to be more emotional and show pain, and men more stoic.

In vertebrates, endogenous opioids are neuromodulators that moderate pain by interacting with opioid receptors. Opioids and opioid receptors occur naturally in crustaceans and, although at present no certain conclusion can be drawn, their presence indicates that lobsters may be able to experience pain. Opioids may mediate their pain in the same way as in vertebrates. Veterinary medicine uses, for actual or potential animal pain, the same analgesics and anesthetics as used in humans.