paina complex experience consisting of a physiological and emotional response to a noxious stimulus. Pain is a warning mechanism that protects an organism by influencing it to withdraw from harmful stimuli; it is primarily associated with injury or the threat of injury. For a more complete discussion of the physiology of pain, see nervous system, human: Pain.

Pain is subjective and difficult to quantify because it has both an affective and a sensory component. Although the neuroanatomic basis of pain reception develops before birth, individual pain responses are learned in early childhood and are affected by social, cultural, psychological, cognitive, and genetic factors, among others. These factors account for differences in pain tolerance among humans. Athletes, for example, may be able to withstand or ignore pain while engaged in a sport, and certain religious practices may require participants to endure pain that seems intolerable to most people.

An important function of pain is to alert the body to potential damage (nociception). The pain sensation, however, is only one part of the nociceptive response, which may include an increase in blood pressure, an increase in heart rate, and a reflexive withdrawal from the noxious stimulus. Acute pain can arise from breaking a bone or touching a hot surface. During acute pain an immediate, intense feeling of short duration, sometimes described as a sharp, pricking sensation, is followed by a dull, throbbing sensation. Chronic pain, which is often associated with diseases such as cancer or arthritis, is more difficult to locate and treat. If pain cannot be alleviated, psychological factors such as depression and anxiety can intensify the condition.

Physiology of pain

In spite of its subjective nature, most pain is associated with tissue damage and has a physiological basis. Not all tissues, however, are sensitive to the same type of injury. For example, although skin is sensitive to burning and cutting, the visceral organs can be cut without generating pain. Overdistension or chemical irritation of the visceral surface, however, will induce pain. Some tissues do not give rise to pain, no matter how they are stimulated; the liver and the alveoli of the lungs are insensitive to almost every stimulus. Thus tissues respond only to the specific stimuli they are likely to encounter and generally are not receptive to all types of damage.

Pain receptors, located in the skin and other tissues, are nerve fibres with endings that can be excited by three types of stimuli—mechanical, thermal, and chemical; some endings respond primarily to one type of stimulation, while other endings can detect all types. Chemical substances produced by the body that excite pain receptors include bradykinin, serotonin, and histamine. Prostaglandins are fatty acids that are released when inflammation occurs and can heighten the pain sensation by sensitizing the nerve endings; this increase in sensitivity is called hyperalgesia.

The dual-phase experience of acute pain noted above is mediated by two types of primary afferent nerve fibres that transmit electrical impulses from the tissues to the spinal cord via the ascending nerve tracts. The A delta fibres are larger and conduct impulses more quickly; therefore, they are associated with the sharp, well-localized pain that first occurs. These fibres are thinly myelinated and are activated by mechanical and thermal stimuli. Smaller, unmyelinated C fibres respond to chemical, mechanical, and thermal stimuli and are associated with the lingering, poorly localized sensation that follows the first, quick sensation of pain.

Pain impulses enter the spinal cord, where they synapse primarily on the dorsal horn neurons in the marginal zone and substantia gelatinosa of the gray matter of the spinal cord. This area is responsible for regulating and modulating the incoming impulses. Two different pathways, the spinothalamic and spinoreticular tracts, transmit impulses to the brainstem and thalamus. Spinothalamic input is thought to effect the conscious sensation of pain, and the spinoreticular tract is thought to effect the arousal and emotional aspects of pain.

Pain signals can be selectively inhibited in the spinal cord through a descending pathway, which originates in the midbrain and ends in the dorsal horn. This analgesic (pain-relieving) response is controlled by neurochemicals called endorphins, which are opioid peptides such as enkephalins that are produced by the body. These substances block reception of stimuli by binding to neural receptors that activate the descending, pain-inhibiting neural pathway. This system can be activated by stress or shock and is probably responsible for the absence of pain associated with a severe injury. It may also explain the differing abilities among individuals to perceive pain.

The origin of pain signals can be unclear to the sufferer. Pain arising from the deep tissues but “felt” in the superficial tissues is called referred pain. This phenomenon results from the proximity of autonomic nerve fibres to neural fibres from the skin and musculature, which allows nerve impulses from one pathway to pass to the other pathway. Phantom limb pain is suffered by an amputee who experiences pain in the missing limb. This phenomenon occurs because the nerve trunks that connected the now absent limb to the brain still exist and are capable of being excited. The brain continues to interpret stimuli from these fibres as arriving from what it had previously learned was the limb.

The theory of pain that most accurately accounts for the physical and psychological aspects of pain is the gate-control theory. According to this model, the perception of pain depends on a neural mechanism in the substantia gelatinosa layer of the dorsal horn. This mechanism acts as a synaptic gate that modulates the pain sensation from myelinated and unmyelinated peripheral nerve fibres and the activity of inhibitory neurons. Thus stimulation of nearby nerve endings can inhibit the nerve fibres transmitting pain signals, which explains the relief that can occur when an injured area is stimulated by pressure or rubbing.

Psychology of pain

The perception of pain results from the brain’s processing of new sensory input with existing memories and emotions, in the same way that other perceptions are produced. Childhood experiences, cultural attitudes, heredity, and gender are factors that contribute to the development of each individual’s perception of and response to different types of pain. Although some people may be able physiologically to withstand pain better than others, cultural factors rather than heredity usually account for this ability.

The point at which a stimulus begins to become painful is the pain perception threshold; most studies have found this point to be relatively similar among disparate groups of people. However, the pain tolerance threshold, the point at which pain becomes unbearable, varies significantly among these groups. A stoical, nonemotional response to an injury may be a sign of bravery in certain cultural or social groups, but this behaviour can also mask the severity of an injury to an examining physician.

Depression and anxiety can lower both types of pain thresholds; anger or excitement, however, can obscure or lessen pain temporarily. Feelings of emotional relief can also lessen a painful sensation. The context of pain and the meaning it has for the sufferer also determine how pain is perceived.

Pain associated with certain psychiatric conditions is believed to arise and be maintained by psychological forces alone. Somatoform disorders, psychosis, and depression may be accompanied by complaints of chronic pain. Although chronic pain often gives rise to depression, sometimes the order is reversed, and vague localized pain for which no physiological cause can be found actually masks depression.

Alleviation of pain

Attempts to relieve pain should address both the physiological and psychological aspects of pain. The reduction of anxiety, for example, may lessen the amount of medication needed to alleviate the pain. Acute pain is generally the easiest to control; medication and rest are often effective treatments. Some pain, however, may defy treatment and persist for years. This chronic pain can be compounded by hopelessness and anxiety.

Opiates are the most potent pain-relieving medications and are used to treat severe pain. Opium, the dried juice of the opium poppy (Papaver somniferum), is one of the oldest analgesics. Morphine, a powerful opiate, is an extremely effective analgesic. These narcotic alkaloids mimic the endorphins by binding to their receptors and blocking or reducing the activation of pain neurons. Use of these narcotics must be monitored not only because opiates are addictive substances but also because the patient can develop a tolerance to them and may require progressively greater doses to achieve the desired level of pain relief. Significant side effects such as depression and nausea also limit the usefulness of opiates. Consequently, these narcotics are not prescribed for long-term therapy. Opiates are used to lessen pain after surgery and to treat patients with terminal illnesses such as cancer.

Extracts of the bark of the willow tree contain the active ingredient salicin and have been used since antiquity to relieve pain. The modern non-narcotic analgesic salicylates, such as aspirin (acetylsalicylic acid), and salicylate-like medications, such as acetaminophen, are less potent than the opiates but are nonaddictive. They are often used to reduce pain resulting from inflammation. Salicylates block the conversion of arachidonic acid (a fatty acid) to prostaglandins, which enhance sensitivity to pain.

Psychotropic medications, including antidepressants and tranquilizers, are used to treat pain that is thought to result from psychological causes alone. These medications reduce anxiety and alter the perception of the pain. Pain seems to be alleviated in a similar manner by hypnosis, placebos, and psychotherapy. The psychological expectation of relief is itself a potent pain relieverWhile the reasons for why an individual may report pain relief after taking a placebo or following psychotherapy remain unclear, researchers believe that the expectation of relief is stimulated by dopamine release in the region of the brain known as the nucleus accumbens. Activity in the nucleus accumbens is linked to increased dopamine activity and is associated with the placebo effect, in which pain relief is reported following treatment with a placebo.

Specific nerves can be blocked in cases in which pain is restricted to an area that has few sensory nerves. Phenol is a neurolytic that permanently destroys nerves; lidocaine can be used for temporary pain relief. Surgical severing of nerves is rarely performed because it can produce serious side effects such as motor loss or relocalized pain.

Some pain may be treated by electrical stimulation through electrodes placed on the skin above the painful area. The stimulation of additional peripheral nerve endings has an inhibitory effect on the nerve fibres generating the pain. This treatment is based on the same process described earlier that allows pain to be inhibited by rubbing the painful area. Acupuncture, compresses, and heat treatment may operate by the same mechanism.

Chronic pain, defined generally as pain that has persisted for at least six months, presents the greatest challenge in pain management. Unrelieved chronic discomfort can cause psychological complications such as hypochondriasis, depression, sleep disturbances, loss of appetite, and feelings of helplessness. In spite of these negative effects, psychological benefits such as increased attention, sympathy, and support may prolong pain by reinforcing the patient’s behaviour.

Pain clinics offer a multidisciplinary approach to chronic pain treatment. A distinction is first made between pain behaviour that is a direct response to a noxious stimulus and that which is learned. If many pain relief methods have been attempted with little success, therapy may include de-emphasizing medication and teaching the patient how to live with the pain.