VASOACTIVE INTESTINAL POLYPEPTIDE AND NEUROPEPTIDE-Y ACT INDIRECTLY TO INCREASE NEURITE OUTGROWTH OF DISSOCIATED DORSAL-ROOT GANGLION-CELLS

Recent studies suggest that rearrangement of synaptic circuitry of pri mary afferent neurons in the spinal cord may contribute, in part, to h yperalgesia that is often associated with peripheral nerve injury. Thi s study of cultured adult rat dorsal root ganglion cells examined whet her vasoactive intestinal polypeptide and neuropeptide Y, which are up -regulated in sensory neurons following nerve transection, possibly co ntribute to the morphological alterations induced by nerve injury. Neu rite outgrowth of dissociated dorsal root ganglion cells was examined two weeks following either sciatic nerve transection or intrathecal ad ministration of test agents via osmotic pumps. Dissociated cells taken from rats with transected sciatic nerve or following intrathecal admi nistration of either vasoactive intestinal polypeptide or neuropeptide Y had a significant increase in the percentage of cells with neurites as compared to dorsal root ganglion cells taken from normal animals. Intrathecal administration, into rats with nerve lesion, of the vasoac tive intestinal polypeptide and neuropeptide Y antagonists, vasoactive intestinal polypeptide((10-28)) and alpha-trinositol, respectively, s ignificantly attenuated the nerve injury-induced increase in neurite o utgrowth. Vasoactive intestinal polypeptide and neuropeptide Y had no influence on neurite outgrowth when applied to normal dissociated dors al root ganglion cells, however, when added to cells co-cultured with spinal cord explants, both peptides significantly increased the percen tage of cells with neurites. K252a, a protein kinase inhibitor, attenu ated the trophic action of neuropeptide Y, but not that of vasoactive intestinal polypeptide. The action of vasoactive intestinal polypeptid e on neurite outgrowth was attenuated by the protein kinase A inhibito r, the Rp-isomer of adenosine-3',5'-cyclic monophosphorothioate. The r esults suggest that the peptides may contribute, indirectly, to the ne rve injury-induced increase in neurite outgrowth of sensory neurons vi a separate spinally-derived neurotrophic factors and the study provide s further insight into the possible mechanisms underlying hyperalgesia associated with nerve injury. Copyright (C) 1996 IBRO. Published by E lsevier Science Ltd.