HUMAN AND RAT PRIMARY C-FIBER AFFERENTS STORE AND RELEASE SECRETONEURIN, A NOVEL NEUROPEPTIDE

Secretoneurin is a recently discovered neuropeptide derived from secre togranin II (SgII). Since this peptide could be detected in the dorsal horn of the spinal cord we studied whether it is localized in and rel eased from primary afferent neurons. Secretoneurin was investigated wi th immunocytochemistry and radioimmunoassay in spinal cord, dorsal roo t ganglia and peripheral organs. SgII mRNA was determined in dorsal ro ot ganglia. Normal rats and rats pre-treated neonatally with capsaicin to destroy selectively polymodal nociceptive (C-) fibres were used. S lices of dorsal spinal cord were perfused in vitro for release experim ents. Immunocytochemistry showed a distinct distribution of secretoneu rin-immunoreactivity (IR) in the spinal cord and lower brainstem. A pa rticularly high density of fibres was found in lamina I and outer lami na II of the caudal trigeminal nucleus and of the spinal cord. This di stribution was qualitatively identical in rat and human post-mortem ti ssue. Numerous small diameter and some large dorsal root ganglia neuro ns were found to contain SgII mRNA. Capsaicin treatment led to a marke d depletion of secretoneurin-IR in the substantia gelatinosa, but not in other immunopositive areas of the spinal cord and to a substantial loss of small (<25 mu m) SgII-mRNA-containing dorsal root ganglia neur ons. Radioimmunoassay revealed a significant decrease of secretoneurin -IR in the dorsal spinal cord, the trachea, heart and urinary bladder of capsaicin-treated rats. Perfusion of spinal cord slices with capsai cin as well as with 60 mM potassium led to a release of secretoneurin- IR. In conclusion, secretoneurin is a neuropeptide which is stored in and released from capsaicin-sensitive, primary afferent (C-fibre) neur ons. It may, therefore, be a novel peptidergic modulator of pain trans mission or of C-fibre mediated non-nociceptive information.