HYPERALGESIA INDUCED BY PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE IN THE MOUSE SPINAL-CORD

The aim of the present study was to evaluate the distribution of pitui tary adenylate cyclase-activating polypeptide (PACAP)-like immunoreact ivity in the mouse spinal cord using an antibody against PACAP38 and t o determine the behavioral profile, particularly with respect to hyper algesia, of PACAP38 given intrathecally (i.t.) in the mouse. Immunorea ctivity to PACAP38 was detected in numerous nerve fibers in the superf icial layers of the dorsal horn of cervical, thoracic, lumbar and sacr al segments and a few fibers extended into the deeper layers of the sp inal cord. In addition, PACAP-like immunoreactivity were seen in the i ntermediolateral cell column of the thoracic and sacral segments. In b ehavioral studies, PACAP38 (0.05-0.5 mu g) produced a dose-dependent d ecrease of the tail-flick latency when given i.t. in the mouse. At hig her doses (1-10 mu g), PACAP38 given i.t. elicited biting and scratchi ng behaviors lasting 10-20 min after the injection. PACAP at high dose s (1-10 mu g) also produced licking at tail, paw and penis and intense grooming behaviors immediately after the i.t. injection. Similar to s ubstance P, these behaviors produced by PACAP can be considered as pai n-like syndrome. These findings suggest that PACAP may be a sensory ne urotransmitter involved in nociceptive signalling in the mouse spinal cord.