Alteration of PACAP distribution and PACAP receptor binding in the rat sensory nervous system following sciatic nerve transection

Pituitary adenylate cyclase activating polypeptide (PACAP) is a widely expr essed neuropeptide that has been involved in nerve regeneration, neurone su rvival and nociception. In this study, the distribution of PACAP and PACAP- receptors were investigated in rat dorsal root ganglia (DRG), spinal cord a nd medulla oblongata at 3, 7 or 14 days following unilateral sciatic nerve transection using immunohistochemistry, I-125-PACAP-binding and in situ hyb ridisation. In control (contralateral side) DRG, about 30% of the nerve cel l bodies (92% being small) were PACAP-immunoreactive (PACAP-IR). In the spi nal cord, PACAP-IR fibres were seen in laminae I-II but not in the gracile nuclei. Following sciatic nerve transection, PACAP-IR fibres appeared in th e gracile nuclei and occasionally in the deeper laminae of the dorsal horn consistent with the relative increase in larger PACAP-IR DRG neurones. Howe ver, the relative number of small PACAR-IR neurones was significantly lower on the transected side as compared to the control side suggesting a dual r eaction for PACAP in the DRG following nerve injury. I-125-PACAP-binding wa s found in laminae I-II, around the central canal and in the gracile nuclei but not in the DRG. At 14 days after transection, I-125-PACAP-binding dens ity was significantly reduced in the ipsilateral dorsal horn. PACAP-recepto r (PAC(1)) mRNA was detected in neurones of the dorsal and ventral horn and in the gracile nuclei with no overt changes observed after transection. Ve ry few DRG nerve cell bodies contained PAC(1) mRNA. The findings are consis tent with a role for PACAP both in nociception and regeneration. (C) 2000 E lsevier Science B.V. All rights reserved.