Efficacy of systemic morphine suggests a fundamental difference in the mechanisms that generate bone cancer vs. inflammatory pain

Nancy M. Luger, Mary Ann C Sabino, Matthew J. Schwei, David B. Mach, James D. Pomonis, Cathy P. Keyser, Michael Rathbun, Denis R. Clohisy, Prisca Honore, Tony L. Yaksh, Patrick W Mantyh

Research output: Contribution to journalArticle

158 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)397-406
Number of pages10
JournalPain
Volume99
Issue number3
DOIs
StatePublished - Oct 2002
Externally publishedYes

Fingerprint

Bone Neoplasms
Morphine
Pain
Cancer Pain
Freund's Adjuvant
Naloxone
Chronic Pain
Femur
Analgesics
Lung Neoplasms
Neoplasms
Prostatic Neoplasms
Quality of Life
Breast Neoplasms
Bone and Bones
Drug Therapy
Injections

Keywords

  • Behavior
  • Hyperalgesia
  • Inflammation
  • Nociception
  • Opioid
  • Tumor

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Neuroscience(all)
  • Pharmacology
  • Clinical Psychology

Cite this

Efficacy of systemic morphine suggests a fundamental difference in the mechanisms that generate bone cancer vs. inflammatory pain. / Luger, Nancy M.; Sabino, Mary Ann C; Schwei, Matthew J.; Mach, David B.; Pomonis, James D.; Keyser, Cathy P.; Rathbun, Michael; Clohisy, Denis R.; Honore, Prisca; Yaksh, Tony L.; Mantyh, Patrick W.

In: Pain, Vol. 99, No. 3, 10.2002, p. 397-406.

Research output: Contribution to journalArticle

Luger, NM, Sabino, MAC, Schwei, MJ, Mach, DB, Pomonis, JD, Keyser, CP, Rathbun, M, Clohisy, DR, Honore, P, Yaksh, TL & Mantyh, PW 2002, 'Efficacy of systemic morphine suggests a fundamental difference in the mechanisms that generate bone cancer vs. inflammatory pain', Pain, vol. 99, no. 3, pp. 397-406. https://doi.org/10.1016/S0304-3959(02)00102-1
Luger, Nancy M. ; Sabino, Mary Ann C ; Schwei, Matthew J. ; Mach, David B. ; Pomonis, James D. ; Keyser, Cathy P. ; Rathbun, Michael ; Clohisy, Denis R. ; Honore, Prisca ; Yaksh, Tony L. ; Mantyh, Patrick W. / Efficacy of systemic morphine suggests a fundamental difference in the mechanisms that generate bone cancer vs. inflammatory pain. In: Pain. 2002 ; Vol. 99, No. 3. pp. 397-406.
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