Effects of peripheral axotomy on cholecystokinin neurotransmission in the rat spinal cord

Because cholecystokinin (CCK) acts as a "functional" endogenous opioid anta gonist, it has been proposed that changes in central CCKergic neurotransmis sion might account for the relative resistance of neuropathic pain to the a nalgesic action of morphine, This hypothesis was addressed by measuring CCK -related parameters 2 weeks after unilateral sciatic nerve section in rats. As expected, significant decreases (-25-38%) in the tissue concentrations and in vitro release of both substance P and calcitonin gene-related peptid e were noted in the dorsal quadrant of the lumbar spinal cord on the lesion ed side. In contrast, the tissue levels and in vitro release of CCK were un changed in the same area in lesioned rats. Measurements in dorsal root gang lia at L4-L6 levels revealed no significant changes in proCCK mRNA after th e lesion. However, sciatic nerve section was associated with a marked ipsil ateral increase in both CCK-B receptor mRNA levels in these ganglia (+70%) and the autoradiographic labeling of CCK-B receptors by [H-3]pBC 264 (+160% ) in the superficial layers of the lumbar dorsal horn. Up-regulation of CCK -B receptors rather than CCK synthesis and release probably contributes to increased spinal CCKergic neurotransmission in neuropathic pain.