EVIDENCE FOR CGRP ACCUMULATION AND ACTIVITY IN EXPERIMENTAL NEUROMAS

Calcitonin gene-related peptide (CGRP) is a potent vasodilator and wid ely distributed neuropeptide that may participate in the injury respon se of peripheral nerve. We examined evidence for the presence of CGRP immunoreactivity (IR) and its activity in experimental neuromas of Spr ague-Dawley rats created by sectioning the midsciatic nerve with resec tion of 2-3 cm of its distal portion and branches. CGRP activity was e valuated by measuring local blood flow in neuromas using hydrogen pola rography and laser-Doppler flowmetry. At all time points studied after nerve section (24 h, 48 h, 7 days, 14 days) there was a rise in local blood flow in the neuroma stumps. At 48 h the hyperemia was maximum b ut was reversed by topical application of human CGRP(8-37), a specific CGRP-receptor antagonist. CGRP presence was evaluated by immunohistoc hemistry and radioimmunoassay (RIA). At 24 and 48 h, CGRP IR was inten se and distributed in a globular and diffuse pattern apparently not co nfined to discrete axonlike profiles. At 7 and 14 days, CGRP IR remain ed prominent and was associated with disorganized axonlike profiles, s ometimes directed in a circumferential pattern around the outside of t he neuroma. RIA confirmed rises in CGRP content at 24 and 48 h that ac companied the changes in local blood flow and altered distribution of CGRP IR. CGRP accumulates in a time-related fashion within experimenta l neuromas, where it induces among other possible actions prominent lo cal vasodilatation. CGRP may be important in the regenerative milieu o f injured nerves.