The role of group III metabotropic receptors on opioid tolerance

Yoon, Myung Ha; Lee, Hyung Kon; Kim, Woong Mo; Cho, Soo Young; Kim, Yeok Ok; Cui, Jin Hua

Clinical Research

Neuroanesthesia

Anesthesia and Pain Medicine 2009;4(2):138-141.
Published online April 30, 2009.

The role of group III metabotropic receptors on opioid tolerance

Myung Ha Yoon, Hyung Kon Lee, Woong Mo Kim, Soo Young Cho, Yeok Ok Kim, Jin Hua Cui

¹Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University, Gwangju, Korea . mhyoon@chonnam.ac.kr
²Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, Korea .

Abstract

BACKGROUND
Prolonged exposure to morphine causes tolerance to morphine-induced antinociception, yet the mechanisms of such tolerance are not fully understood. Although group I and II metabolic glutamate receptors (mGluRs) are involved in the modulation of morphine tolerance, the role of the group III mGluRs has not been determined. Therefore, we examined the effect of a group III mGluRs agonist on the morphine tolerance in the spinal cord.
METHODS
An intrathecal infusion of morphine (40 nmol/microl/h) for 5 days was done to examine the development of morphine tolerance in male Sprague-Dawley rats. Noxious radiant heat was applied to the hindpaw and we measured the thermal withdrawal latency. To clarify the role of the group III mGluRs, an intrathecal group III mGluRs agonist (ACPT-III) or saline was administered to the morphine tolerant rats and we observed the change of the thermal withdrawal latency at 15, 30, 60, 90 and 120 min after delivery of ACPT-III.
RESULTS
A continuous intrathecal infusion of morphine significantly increased the thermal withdrawal latency, as compared with the saline infused rats on day 1, with a decline on day 3 and the increase of withdrawal latency totally disappeared on day 5 (tolerance). Intrathecal ACPT-III increased the thermal withdrawal latency in the morphine tolerance rats.
CONCLUSIONS
These results suggest that the group III mGluRs may be involved in the suppression of tolerance to morphine-induced antinociception at the spinal level.

Key Words: analgesia, spinal cord, tolerance, scalp nerve block