An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage (see Merskey, 1991). This definition includes three elements common to most definitions: (1) pain is a sensory experience distinguishable from other sensory modalities—such as temperature or touch; (2) this sensory experience is normally accompanied by an aversive emotional state; and (3) the distinctive sensory-emotional experience of pain sometimes occurs in the absence of tissue damage or physical stimulation that would lead to tissue damage. It is sometimes assumed that pain is subjective and can only be unequivocally identified by self-report. This view has been strongly opposed on the grounds that human adults, human infants and many species of mammals respond to tissue injury in a similar manner. Psychophysical studies (see PSYCHOPHYSICS) of pain show that the sensory experience, and the aversive state, are to some extent dissociable in that a DRUG and brain LESION can modify the emotional state without altering the magnitude of the pain sensation proportionately. This implies that the sensory and emotional aspects of pain depend on pathways in the brain that are, at some level, different.
Neurological theories of pain fall into two classes. SPECIFICITY theories hold that pain is associated with activation of a specific class of sensory afferent neurons (nociceptors; see NOCICEPTION). Pattern theories hold that pain arises when a particular pattern or level of sensory input is detected by the brain, and that the sensory input may be provided by a variety of sensory receptors, not specific nociceptors. In normal tissue, pain is evoked by stimuli which activate a subclass of small myelinated (A-delta fibres; see A FIBRES) and unmyelinated (c FIBRES) neurons with very high thresholds for activation. These neurons, like other sensory neurons, have their cell bodies in the DORSAL ROOT GANGLIA. The nociceptive cells have two processes, one projects distally and terminates as a FREE NERVE ENDING. The other terminates in lamina 1 or lamina 5 of the DORSAL HORN of the SPINAL CORD on relay cells which project to the THALAMUS and BRAINSTEM by two routes. The nociceptive afferents also synapse on INTERNEURONS in layer 1 and 2 that inhibit or excite the relay cells. Relay cell axons cross over to the ascending tracts on the contralateral side of the cord. One group of pathways ascends in the ventrolateral white matter of the cord, and runs through the medial brainstem to the posterior and intralaminar groups of thalamic nuclei, then to the FRONTAL CORTEX and posterior PARIETAL CORTEX. Many fibres in this pathway terminate in the RETICULAR FORMATION and PERIAQUEDUCTAL GREY which have heavy connections with the LIMBIC SYSTEM.
This pathway is thought to be important for the emotional aversive aspect of pain, and for stimulating descending inhibitory pathways. The other group of pathways ascend in the ventrolateral tract and the dorsal columns of the cord, and run through the MIDBRAIN in the MEDIAL LEMNISCUS to the ventrobasal group of thalamic nuclei. The ventrobasal thalamus in turn projects to the SOMATOSENSORY CORTEX. This pathway is thought to be important for the localization and identification of painful events. The role of the cortex in pain remains uncertain as no cortical region essential for pain perception has been discovered.
When a brief, noxious stimulus is applied to a limb, pain is felt in two waves. The first pain has a sharp stinging quality, while the second pain has a burning quality, and the sensation is longer lasting. This represents the waves of excitation from the faster conducting A-delta fibres and the slow conducting C fibres. They are thought to release the neurotransmitters GLUTAMATE and SUBSTANCE P, respectively. Stimulation that would normally be innocuous, may elicit pain from injured tissue because substance P, and other mediators of inflammation, sensitize the injured tissue and the cells in the dorsal horn. The cells of the dorsal horn do not simply relay information from nociceptors to the brain. They integrate information from nociceptors with information from other classes of sensory AFFERENT in the spinal cord, and from the brain, particularly the brainstem. STRESS and drugs such as MORPHINE activate a neural system, which includes the periaqueductal grey and RAPHE NUCLEI, that sends descending fibres down the cord to the dorsal horn. This system acts to inhibit the transmission of information from nociceptors to the dorsal horn relay cells. The descending inhibitory controls are though to explain the fact that humans or animals may appear insensitive to normally painful conditions, such as broken bones, when they are in a state of FEAR or extreme excitement. The neural circuits of descending inhibitory controls contain ENDOGENOUS OPIATES, and it is thought that analgesics (see ANALGESIA) like morphine act by mimicking the actions of the endogenous opiate neurotransmitters in these systems.
