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.

journal_name

Anesth Analg

journal_title

Anesthesia and analgesia

authors

Kim WM,Jeong CW,Lee SH,Kim YO,Cui JH,Yoon MH

doi

10.1213/ANE.0b013e318227824e

subject

Has Abstract

pub_date

2011-10-01 00:00:00

pages

934-40

issue

4

eissn

0003-2999

issn

1526-7598

pii

ANE.0b013e318227824e

journal_volume

113

pub_type

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