title: [Pain-relieving effect of CGRP antagonism on inflammatory pain].
abstract: The neuropeptide calcitonin gene-related peptide (CGRP) is known to play a major role in the pathogenesis of pain syndromes, in particular migraine pain; however, its implication in inflammatory processes is not well known. The CGRP receptor antagonist BIBN4096BS was shown to reduce migraine pain and trigeminal neuronal activity. An analgesic action of this compound can also be found in rats with induced acute inflammation by injection of complete Freund's adjuvant (CFA) in one hindpaw. In this model the compound reduced inflammatory pain and spinal neuronal activity. Behavioral experiments (Randall-Selitto test) revealed a reversal of the CFA-induced mechanical hyperalgesia in rats after systemic drug administration. In vivo electrophysiological studies performed in rats injected with CFA using recordings of wide dynamic range neurons in deep dorsal horn layers of the lumbar spinal cord, confirmed a reduction of neuronal activity after systemic drug administration. The same considerable amount of reduction occurred after topical administration onto the paw with resulting systemic plasma concentrations in the low nanomolar range. Spinal administration of BIBN4096BS did not modify the neuronal activity in the CFA model which suggests that peripheral blockade of CGRP receptors by BIBN4096BS significantly alleviates inflammatory pain.
authors.affiliation: Klinik für Neurologie, Universitätsmedizin Mainz, Langenbeckstr. 1, 55128, Mainz, Deutschland, silke.hirsch@unimedizin-mainz.de.
authors.forename: S
authors.initials: S
authors.lastname: Hirsch
authors.forename: F
authors.initials: F
authors.lastname: Birklein
mesh_terms: D000818:Animals; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D059350:Chronic Pain / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects
chemical_list: D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; C491562:Crcp protein, rat; D010879:Piperazines; D011799:Quinazolines; D018015:Receptors, Calcitonin Gene-Related Peptide; C406305:olcegepant