Pain: neuroanatomy, chemical mediators, and clinical implications.
Most pain information begins at simple, naked nerve endings called nociceptors that form a functional pain unit with nearby tissue capillaries and mast cells. Tissue injury causes these nerve terminals to depolarize, an event that is propagated along the entire afferent fiber eventuating in sensory impulses reaching the spinal cord. This firing of primary afferent fibers at the site of tissue injury causes axonal release of vesicles containing neuropeptides such as substance P, which acts in an autocrine and paracrine manner to sensitize the nociceptor and increase its rate of firing. Cellular damage and inflammation increase concentrations of other chemical mediators such as histamine, bradykinin, and prostaglandins in the area surrounding functional pain units. These additional mediators act synergistically to augment the transmission of nociceptive impulses along sensory afferent fibers. Primary fibers travel from the periphery to the dorsal horn where they synapse on secondary neurons and interneurons. When activated, interneurons exert inhibitory influences on further pain signal trafficking. Efferent supraspinal influences, in turn, determine the activity of interneurons by releasing a variety of neurotransmitter substances, thus resulting in a high degree of modulation of nociception within the dorsal horn. Events occurring in the periphery and in the dorsal horn can cause a dissociation of pain perception from the presence or degree of actual tissue injury. These phenomena involve many chemical mediators and receptor systems, and can increase pain experience qualitatively, quantitatively, temporally, and spatially. The complexity and plasticity of the nociceptive system can make clinical management of pain difficult. Undestanding the structure and chemical signals associated with this system can improve the use of existing analgesics and provide targets for development of newer and more specific pain-fighting drugs.
McHugh
J M
JM
Duke University School of Nursing, Durham, North Carolina, USA.
McHugh
W B
WB
D000344:Afferent Pathways / Q000033:anatomy & histology* / Q000502:physiology*; D001923:Brain Chemistry / Q000502:physiology*; D006801:Humans; D018377:Neurotransmitter Agents / Q000502:physiology*; D010146:Pain / Q000451:nursing / Q000503:physiopathology*
D018377:Neurotransmitter Agents