Pituitary adenylate cyclase activating peptide: a neuropeptide in the sensory nervous system

Abstract: This thesis deals with the expression of pituitary adenylate cyclase activating peptide (PACAP) in sensory C-type cells and primary afferent fibres and its possible role in nociceptive transmission. PACAP-expression, -release, -synthesis and -function were investigated in a series of measurements using immunocytochemistry, radioimmunoassay, in situ hybridization histochemistry, Northern blot, electrophysiology, superficial spinal perfusion and nerve injury. PACAP expresses normally in C-type sensory neurons and primary afferent fibres in rats and coexists with SP/CGRP in nerve fibres of the superficial laminae of the dorsal horn and of the peripheral tissues, of organs with prominent sensory innervation. Capsaicin releases PACAP from the central terminals of primary C-type afferents in the spinal cord, supporting the view that PACAP participates in transmission in the spinal dorsal horn as a messenger. Intrathecal administration of PACAP suppresses the C-fibre evoked flexion reflex and formalin-induced pain-related behaviour. Taken together, the evidence shows that PACAP may act as a modulator in nociception and has antinociceptive effects. Following sciatic nerve injury, the synthesis of PACAP in the dorsal root ganglia is upregulated and the concentrations of PACAP in the spinal cord and the proximal nerve stumps enhanced, indicating that PACAP plays a role in the postaxotomy repair and restoration process. It may act as a neurotropic factor or as a survival factor in adaptation to nerve injury. The findings are consistent with the hypothesis that PACAP may be important both in sensory transmission and in regeneration.