Basic pathways of nociceptive pain – Peripheral pain stimuli are detected by primary afferent nociceptors, which transmit pain centrally via unmyelinated C fibers or thinly myelinated Aδ fibers.

The cell bodies of the primary afferent nociceptors are located in the dorsal root ganglia (DRG) and their fibers terminate on second order neurons in the dorsal horn of the spinal cord.

Lissauer’s tract consists of smaller fibers that congregate together prior to synapsing in the dorsal-most layers of the dorsal horn. Most nociceptive input from the periphery transmits to Rexed layers I (marginal layer), II (substantia gelatinosa) or V (the deepest portion of the nucleus proprius, which consists of Rexed layers III-V). Excitatory neuromediators related to pain transmission identified in the dorsal horn have included glutamate, substance P, calcitonin gene-related peptide (CGRP), and bradykinin. The aforementioned dorsal horn layers, in turn, project to the ascending pathways. Spinal cord pathways that have been implicated in ascending nociceptive pain signal transmission include the spinothalamic tract, spinoreticular tract, spinomesencephalic tract and postsynaptic dorsal column tract.

The spinothalamic tract is the most important of the ascending tracts in relation to pain transmission. Most of its neurons arise from Rexed lamina I. Along with fibers arising from laminae II and V, this pathway (termed the neospinothalamic pathway) transmits the sensory and discriminative aspects of pain to the lateral thalamus and sensorimotor cortex. Neurons residing in deeper Rexed laminae (VI, IX) contribute to spinothalamic tract fibers projecting to the medial thalamus, reticular formation, periaqueductal gray, hypothalamus, and other areas of the limbic system. This pathway (the paleospinothalamic tract) is associated with the affective aspects of pain.

Other portions of the brain involved with higher nociceptive signal processing (cingulate cortex, lentiform nucleus, insula, anterior cingulate, and prefrontal cortex) have been demonstrated on functional MRI and PET studies (Gybels, 1985).