title: Evidence for anti-inflammatory and putative analgesic effects of a monoclonal antibody to calcitonin gene-related peptide.
abstract: BACKGROUND
  Calcitonin gene-related peptide (CGRP) is a powerful pro-inflammatory mediator thought to play a significant role in the development of inflammation and pain. We investigated the role of CGRP in trigeminal inflammatory pain by determining the ability of a monoclonal antibody to CGRP to modify central Fos expression in response to stimulation of the inflamed ferret tooth pulp. We also assessed the effect of the antibody on pulpal inflammation.
  
  
  METHODS
  Ten adult ferrets were prepared under anaesthesia to allow stimulation of the upper and lower left canine pulps, recording from the digastric muscle and intravenous injections at subsequent experiments. In all animals, pulpal inflammation was induced by introducing human caries into a deep buccal cavity. Four days later animals were treated intravenously with either CGRP antibody (n=5) or vehicle (n=5). After a further 2 days animals were re-anaesthetised and the tooth pulps stimulated at 10 times jaw-opening reflex threshold. Brainstems and tooth pulps were processed immunohistochemically for Fos and the common leucocyte marker CD45, respectively.
  
  
  RESULTS
  Fos was expressed in ipsilateral trigeminal subnuclei caudalis (Vc) and oralis (Vo). Significantly fewer Fos-positive nuclei were present within Vc of CGRP antibody-treated animals (p=0.003 vs vehicle-treated). Mean percentage area of staining for CD45 was significantly less in antibody-treated animals (p=0.04 vs vehicle-treated).
  
  
  CONCLUSIONS
  This is the first direct evidence that sequestration of CGRP has anti-inflammatory and putative analgesic effects. Previous studies using this Fos model have demonstrated that it is able to predict clinical analgesic efficacy. Thus these data indicate that this antibody may have analgesic effects in dental pain and other types of inflammatory-mediated transmission, and suggest that this is in part due to peripheral anti-inflammatory effects.
authors.affiliation: Unit of Oral & Maxillofacial Medicine & Surgery, School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield S10 2TA, UK.
authors.forename: K E
authors.initials: KE
authors.lastname: Bowler
authors.forename: M A
authors.initials: MA
authors.lastname: Worsley
authors.forename: L
authors.initials: L
authors.lastname: Broad
authors.forename: E
authors.initials: E
authors.lastname: Sher
authors.forename: R
authors.initials: R
authors.lastname: Benschop
authors.forename: K
authors.initials: K
authors.lastname: Johnson
authors.forename: J M
authors.initials: JM
authors.lastname: Yates
authors.forename: P P
authors.initials: PP
authors.lastname: Robinson
authors.forename: F M
authors.initials: FM
authors.lastname: Boissonade
mesh_terms: D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism; D003782:Dental Pulp / Q000276:immunology / Q000378:metabolism; D005260:Female; D005289:Ferrets; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D010147:Pain Measurement / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D015740:Calcitonin Gene-Related Peptide