Involvement of PACAP receptor in primary afferent fibre-evoked responses of ventral roots in the neonatal rat spinal cord

1 The role of PACAP receptor in nociceptive transmission was investigated i n vitro using maxadilan, a PACAP receptor selective agonist and max.d.4, a PACAP receptor selective antagonist. 2 Potentials, from a ventral root (L3-L5) of an isolated spinal cord prepar ation or a spinal cord-saphenous nerve-skin preparation from 0-3-day-old ra ts, were recorded extracellularly. 3 In the isolated spinal cord preparation, single shock stimulation of a do rsal root at C-fibre strength induced a slow depolarizing response lasting about 30 s (slow ventral root potential; slow VRP) in the ipsilateral ventr al root of the same segment. Bath-application of max.d.4 (0.01-3 muM) inhib ited the slow VRP in a concentration-dependent manner. 4 In the spinal cord-saphenous nerve-skin preparation, application of capsa icin (0.1 muM) to the skin evoked a depolarization of the ventral root. Thi s response was also depressed by max.d.4 (1 muM). 5 Application of maxadilan evoked a long-lasting depolarization in a concen tration-dependent manner in the spinal cord preparation. In the presence of max.d.4 (0.3 muM), the concentration response curve of maxadilan was shift ed to the right. 6 Reverse transcription-polymerase chain reaction (RT-PCR) experiments demo nstrated the existence of PACAP receptor and VPAC(2) receptor in the neonat al rat spinal cord and [I-125]-PACAP27 binding was displaced almost complet ely by maxadilan and max.d.4, but not by vasoactive intestinal peptide (VIP ). These data indicate that PACAP receptor is dominantly distributed in the neonatal rat spinal cord. 7 The present study suggests that PACAP receptor may play an excitatory rol e in nociceptive transmission in the neonatal rat spinal cord.