title: The CGRP receptor antagonist BIBN4096BS peripherally alleviates inflammatory pain in rats.
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.
authors.affiliation: Department of CNS Diseases Research, Birkendorfer Strasse 65, Boehringer Ingelheim Pharma GmbH & Co KG, 88397 Biberach, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Hirsch
authors.forename: Laura
authors.initials: L
authors.lastname: Corradini
authors.forename: Stefan
authors.initials: S
authors.lastname: Just
authors.forename: Kirsten
authors.initials: K
authors.lastname: Arndt
authors.forename: Henri
authors.initials: H
authors.lastname: Doods
mesh_terms: D000287:Administration, Topical; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001522:Behavior, Animal; D015740:Calcitonin Gene-Related Peptide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D005620:Freund's Adjuvant; D007249:Inflammation / Q000150:complications / Q000188:drug therapy*; D020910:Ketorolac / Q000627:therapeutic use; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use; D009474:Neurons / Q000187:drug effects; D010003:Osteoarthritis / Q000139:chemically induced / Q000150:complications; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000187:drug effects; D010879:Piperazines / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D011799:Quinazolines / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000503:physiopathology
chemical_list: D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010879:Piperazines; D011799:Quinazolines; D009020:Morphine; D005620:Freund's Adjuvant; D015740:Calcitonin Gene-Related Peptide; C406305:olcegepant; D020910:Ketorolac