title: Anti-morphine antibody contributes to the development of morphine tolerance in rats.
abstract: Previous studies have shown that tolerance to the antinociceptive effect of morphine develops after a prolonged exposure, but its mechanisms remain unclear. In the present study, we examined whether anti-morphine antibody produced by chronic morphine exposure would contribute to the development of morphine antinociceptive tolerance in rats. Our results showed that anti-morphine antibody was present in rats rendered tolerance to antinociception after intrathecal morphine exposure for seven consecutive days. Superfusion of anti-morphine antibody onto spinal cord slice dose-dependently produced an inward excitatory current in spinal cord dorsal horn neurons using whole-cell patch-clamp recording, which surpassed morphine-induced outward inhibiting current. Co-administration of morphine with a monoclonal antibody (2.4G(2)) against Fc receptors for seven days significantly attenuated the production of anti-morphine antibody as well as the behavioral manifestation of morphine tolerance in same rats. These results indicate that anti-morphine antibody produced by morphine exposure may contribute to the development of morphine tolerance possibly through counteracting the inhibitory morphine effect on spinal cord dorsal horn neurons.
authors.affiliation: MGH Center for Translational Pain Research, Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Hyangin
authors.initials: H
authors.lastname: Kim
authors.forename: Saecheol
authors.initials: S
authors.lastname: Oh
authors.forename: Backil
authors.initials: B
authors.lastname: Sung
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Tian
authors.forename: Liling
authors.initials: L
authors.lastname: Yang
authors.forename: Shuxing
authors.initials: S
authors.lastname: Wang
authors.forename: Jianren
authors.initials: J
authors.lastname: Mao
mesh_terms: D000701:Analgesics, Opioid / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004361:Drug Tolerance / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D009020:Morphine / Q000276:immunology* / Q000494:pharmacology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000701:Analgesics, Opioid; D000906:Antibodies; D009020:Morphine