Evidence for a localization of [(3)H]nociceptin binding sites on medullar primary afferent fibers

The ORL1 receptor (opioid receptor-like 1) and its endogenous ligand, nociceptin, are involved in nociperception. We have studied, in a deafferented animal model, the modification of medullar [(3)H]nociceptin binding site density. A rhizotomy was carried out in rats at the cervicothoracic level, and the dorsal afferent fibers from C5 to T1 were lesioned. Seven days after surgery, animals were sacrificed, and the binding of [(3)H]nociceptin (2 nM) was then performed on spinal cord sections. An autoradiographic analysis revealed a significant reduction (-18%) of [(3)H]nociceptin binding site density in the dorsal horn ipsilateral to the deafferentation compared with the contralateral side of the lesion. In the ventral horn, no significant difference (-5%) of binding was observed in the ipsilateral side of the deafferentation compared with the contralateral side. Thus, [(3)H]nociceptin binding sites appear to be located mainly on either interneurons or deutoneurons of the spinal cord, because the bulk of the labeling is spared by the lesion. However, the significant reduction of labeling that occurs on the dorsal part of the ipsilateral side to the lesion indicates that [(3)H]nociceptin binding sites are also present on these dorsal afferent fibers.