The intrathecally administered kappa-2 opioid agonist GR89696 and interleukin-10 attenuate bone cancer-induced pain through synergistic interaction.

Abstract

BACKGROUND:

Although bone cancer-related pain is one of the most disruptive symptoms in patients with advanced cancer, patients are often refractory to pharmacological treatments; thus, more effective treatments for bone cancer pain are needed. We evaluated the analgesic efficacy of and interaction between intrathecal GR89696, a κ(2)-opioid receptor agonist, and interleukin (IL)-10 in a rat model of bone cancer pain.

METHODS:

The rat model of bone cancer pain was produced by right tibia intramedullary injection of rat breast cancer cells, and an intrathecal catheterization was performed. Ten days later, a paw-withdrawal threshold to mechanical stimulus by von Frey hairs was measured using the up-down method, after intrathecal administration of GR89696 and IL-10. The interaction between the 2 drugs was also evaluated using an isobolographic analysis.

RESULTS:

Intrathecal GR89696 and IL-10 significantly increased the paw withdrawal threshold of the cancer cell-implanted rat, in a dose-dependent manner, with 50% effective dose values (95% confidence interval) of 50.78 μg (31.80-80.07μg) and 0.83 μg (0.59-1.15 μg), respectively. Isobolographic analysis revealed a synergistic interaction between intrathecal GR89696 and IL-10.

CONCLUSIONS:

Intrathecally administered GR89696 and IL-10 attenuated bone cancer-induced pain, and the 2 drugs interacted synergistically in the spinal cord. These results raise the intriguing possibility of κ(2)-opioid receptor agonists and IL-10 as a new therapeutic approach for the management of bone cancer-associated pain.

• Authors: Woong Mo Kim, Cheol Won Jeong, Seong Heon Lee, Yeo Ok Kim, Jin Hua Cui, Myung Ha Yoon
• Journal: Anesthesia and analgesia (Anesth Analg) Vol. 113 Issue 4 Pg. 934-40 (Oct 2011) ISSN: 1526-7598 [Electronic] United States
• PMID: 21788320 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Opioid
• Anti-Inflammatory Agents
• Piperazines
• Pyrrolidines
• Receptors, Opioid, kappa
• kappa(2) opioid receptor
• GR 89696
• Interleukin-10

Topics

• Analgesics, Opioid (administration & dosage)
• Animals
• Anti-Inflammatory Agents (administration & dosage)
• Behavior, Animal (drug effects)
• Bone Neoplasms (complications, secondary)
• Breast Neoplasms (pathology)
• Cell Line, Tumor
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Synergism
• Female
• Injections, Spinal
• Interleukin-10 (administration & dosage)
• Pain (drug therapy, etiology, metabolism, physiopathology)
• Pain Measurement
• Pain Threshold (drug effects)
• Piperazines (administration & dosage)
• Pyrrolidines (administration & dosage)
• Rats
• Rats, Sprague-Dawley
• Receptors, Opioid, kappa (agonists, metabolism)
• Tibia (pathology)
• Time Factors