Bone cancer pain: from model to mechanism to therapy.
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. Ten days following tumor implantation into the intramedullary space of the femur, significant bone destruction and bone cancer pain-related behaviors were observed and progressed in severity over time. A critical question is how closely this model mirrors human bone cancer pain. In a recent publication, 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 10 times that required to block peak inflammatory pain behaviors of comparable magnitude induced by hindpaw injection of complete Freund's adjuvant (CFA; 1-3 mg/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 versus inflammatory pain suggests a fundamental difference in the underlying mechanisms that generate bone cancer versus inflammatory pain. These results indicate that this model will be useful in defining drug therapies that are targeted for complex bone cancer pain syndromes.
Luger
Nancy M
NM
Department of Preventive Sciences, University of Minnesota, Minneapolis, Minnesota, USA.
Mach
David B
DB
Sevcik
Molly A
MA
Mantyh
Patrick W
PW
D000818:Animals; D001859:Bone Neoplasms / Q000150:complications*; D004195:Disease Models, Animal; D006801:Humans; D010146:Pain / Q000209:etiology*; D010166:Palliative Care