title: Efficacy of systemic morphine suggests a fundamental difference in the mechanisms that generate bone cancer vs inflammatory pain.
abstract: Pain is the cancer related event that is most disruptive to the cancer patient's quality of life. Although bone cancer pain is one of the most severe and common of the chronic pains that accompany breast, prostate and lung cancers, relatively little is known about the mechanisms that generate and maintain this pain. Recently, we developed a mouse model of bone cancer pain and 16 days following tumor implantation into the intramedullary space of the femur, significant bone destruction and bone cancer pain-related behaviors were observed. A critical question is how closely this model mirrors human bone cancer pain. In the present study we show that, as in humans, pain-related behaviors are diminished by systemic morphine administration in a dose dependent fashion that is naloxone-reversible. Humans suffering from bone cancer pain generally require significantly higher doses of morphine as compared to individuals with inflammatory pain and in the mouse model, the doses of morphine required to block bone cancer pain-related behaviors were ten times that required to block peak inflammatory pain behaviors of comparable magnitude induced by hindpaw injection of complete Freund's adjuvant (CFA) (1-3mg/kg). As these animals were treated acutely, there was not time for morphine tolerance to develop and the rightward shift in analgesic efficacy observed in bone cancer pain vs. inflammatory pain suggests a fundamental difference in the underlying mechanisms that generate bone cancer vs. inflammatory pain. These results indicate that this model may be useful in defining drug therapies that are targeted for complex bone cancer pain syndromes.
authors.affiliation: Department of Preventive Sciences, Schools of Dentistry and Medicine, University of Minnesota, Minneapolis, MN 55455, USA Department of Neuroscience, Schools of Dentistry and Medicine, University of Minnesota, Minneapolis, MN 55455, USA Department of Psychiatry, Schools of Dentistry and Medicine, University of Minnesota, Minneapolis, MN 55455, USA Cancer Center, Schools of Dentistry and Medicine, University of Minnesota, Minneapolis, MN 55455, USA VA Medical Center, Minneapolis, MN 55417, USA Department of Anesthesiology, University of California San Diego, La Jolla, CA 92093, USA Department of Orthopaedic Surgery and Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Luger
authors.forename: Mary Ann C
authors.initials: MAC
authors.lastname: Sabino
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Schwei
authors.forename: David B
authors.initials: DB
authors.lastname: Mach
authors.forename: James D
authors.initials: JD
authors.lastname: Pomonis
authors.forename: Cathy P
authors.initials: CP
authors.lastname: Keyser
authors.forename: Michael
authors.initials: M
authors.lastname: Rathbun
authors.forename: Denis R
authors.initials: DR
authors.lastname: Clohisy
authors.forename: Prisca
authors.initials: P
authors.lastname: Honore
authors.forename: Tony L
authors.initials: TL
authors.lastname: Yaksh
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Mantyh
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009020:Morphine / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D009020:Morphine