Peripheral and spinal mechanisms of nociception.

Due to the combination of multidisciplinary studies, the last fifteen years have seen a major step forward in our knowledge of nociception. At the peripheral level the role of A delta and C polymodal cutaneous nociceptors is relatively well demonstrated in animal as well as in man. The activation of these nociceptors probably results from both direct effects of the stimulus and indirect effects, mediated by the release of various chemicals. The specific roles of articular, muscular and visceral fine afferent fibers in nociception, is less well understood. Cutaneous A delta and/or C fibers terminate mainly in the superficial zones (laminae I and II outer) of the dorsal horn. The nature of the transmitter (s) released by nociceptive afferents is still unknown. Substance P has long been a candidate but the multiplicity of peptides revealed by immunohistochemical techniques and their coexistence on occasions in the same dorsal root ganglion cells question a unequivocal role of substance P. At the level of the dorsal horn of the spinal cord, nociceptive specific and nociceptive non-specific units have been described in laminae I, II, IV to VI. It is generally held that nociceptive specific neurons are mainly found in the superficial laminae which also contains nociceptive non specific cells. Convergence of cutaneous, muscular and visceral inputs on these neurons is indicative of a role of both cell types in referred pain where consideration must also be given to the possibility of dichotomizing afferent fibers serving cutaneous and visceral territories. The involvement of contralateral ascending pathways (spinothalamic and spinoreticular tracts) in the transmission of nociceptive messages toward supraspinal structures is well established while the role of ipsilateral ascending systems (spino-cervical and dorsal columns post-synaptic fibers) is still questioned. Both segmental and descending modulating controls are exerted at the spinal level. At segmental levels, the inhibitory action of large diameter cutaneous fibers is now well established. The action of fine fibers seems also to be inhibitory. Descending influences are exerted from the periaqueductal gray matter and the ventromedial medulla (mainly the nucleus raphe magnus). They are sustained by serotoninergic and noradrenergic mechanisms and they involve to a lesser extent the endogenous opioids. The physiological function of these descending systems is still sharply discussed.