Involvement of CGRP in peripheral nerve injury-induced behavioral hypersensitivity and chemokine production (CCR5P.260)

Abstract

Abstract Previously, we have observed increased expression of Calcitonin Gene Related Peptide (CGRP), a pro-nociceptive neuropeptide, along with selected cytokines and chemokines, in the lumbar spinal cord following spinal nerve L5 transection (L5Tx, a murine model of neuropathic pain) in BALB/c mice. To further study the effects of CGRP in neuropathic pain, we intrathecally (i.t.) injected a CGRP antagonist (CGRP8-37) into BABL/c mice following L5Tx. Mice injected with CGRP8-37 displayed a reduced L5Tx-induced mechanical hypersensitivity, but not heat hypersensitivity. CGRP8-37 also caused significant reduction of the level of lumbar spinal cord CCL5 (RANTES) post-L5Tx when compared to vehicle injected-mice and non-injected mice. i.t. injection of a CCL5 neutralizing antibody significantly inhibited L5Tx-induced mechanical hypersensitivity. To test whether CGRP played its pro-nociceptive role through stimulating glial response, mixed glial cells were treated with various doses of CGRP. CGRP induced a slight increase of CCL5 24 hours post-treatment, which was correlated with the increased expression of MAP Kinase (MAPK) signaling pathway molecules: p38 and JNK. Thus, CGRP may promote MAPK-mediated glial activation and the subsequent production of CCL5, which potentiate behavioral hypersensitivity following L5Tx.