Rat peripheral nerve components release calcitonin gene-related peptide and prostaglandin E-2 in response to noxious stimuli: Evidence that nervi nervorum are nociceptors

The presence of an intrinsic afferent innervation of nerves and their conne ctive tissues (nervi nervorum) suggests that these neural elements particip ate in sensation and pathological processes affecting nerves. Primary affer ent nociceptors contain and release neuropeptides including calcitonin gene -related peptide, implicated in inflammatory vasodilatation. We sought to e valuate the ability of different peripheral nerve components, in vitro, to release calcitonin gene-related peptide and prostaglandin E-2 in response t o electrical and noxious chemical stimuli, using sensitive enzyme immunoass ays. We observed significant increases in both calcitonin gene-related pept ide and prostaglandin E-2;? in response to a mixture of inflammatory mediat ors (bradykinin, histamine, and serotonin; 10(-5) M) applied to the intact nerves (+37% and +700%, respectively) and isolated sheaths (35% and 430%, r espectively), but not when this mixture was applied to isolated axons. Prox imal (antidromic) but not distal (orthodromic) electrical stimulation also evoked a comparable release of calcitonin gene-related peptide (+30%) from intact nerves. These results suggest that nervi nervorum nociceptors partic ipate in neural inflammation. Capsaicin (10(-6) M) elicited a very large re lease of calcitonin gene-related peptide when applied to either the intact nerve (+400%), isolated sheaths (+500%), or isolated axons (1400%). The lat ter effect was substantially but not completely blocked by Ruthenium Red an d capsazepine, and was completely blocked using a calcium-free bathing solu tion. The results support the presence of capsaicin receptors in peripheral nerve s that can effect calcitonin gene-related peptide release from axons as wel l as from terminals. (C) 1999 IBRO. Published by Elsevier Science Ltd.