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. 2013 May;154(5):700-707.
doi: 10.1016/j.pain.2013.01.002. Epub 2013 Jan 11.

The CGRP receptor antagonist BIBN4096BS peripherally alleviates inflammatory pain in rats

Silke Hirsch  1 , Laura Corradini, Stefan Just, Kirsten Arndt, Henri Doods
Affiliations

The CGRP receptor antagonist BIBN4096BS peripherally alleviates inflammatory pain in rats

Silke Hirsch et al. Pain. 2013 May.

Abstract

Calcitonin gene-related peptide (CGRP) is known to play a major role in the pathogenesis of pain syndromes, in particular migraine pain. Here we focus on its implication in a rat pain model of inflammation, induced by injection of complete Freund adjuvant (CFA). The nonpeptide CGRP receptor antagonist BIBN4096BS reduces migraine pain and trigeminal neuronal activity. Here we demonstrate that the compound reduces inflammatory pain and spinal neuronal activity. Behavioural experiments reveal a reversal of the CFA-induced mechanical hypersensitivity and monoiodoacetate (MIA)-induced weight-bearing deficit in rats after systemic drug administration. To further investigate the mechanism of action of the CGRP antagonist in inflammatory pain, in vivo electrophysiological studies were performed in CFA-injected rats. Recordings from wide dynamic range neurons in deep dorsal horn layers of the lumbar spinal cord confirmed a reduction of neuronal activity after systemic drug application. The same amount of reduction occurred after topical administration onto the paw, with resulting systemic plasma concentrations in the low nanomolar range. However, spinal administration of BIBN4096BS did not modify the neuronal activity in the CFA model. Peripheral blockade of CGRP receptors by BIBN4096BS significantly alleviates inflammatory pain.

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