Effects of Intrathecal Drugs Acting on Metabotropic Glutamate Receptors and Interaction with Morphine on a Rat Incisional Pain

Nah, Song Soo; Bae, Hong Beom; Kim, Seok Jai; Chung, Sung Tae; Choi, Jeong Il; Yoon, Myung Ha; Jeong, Chang Young

Abstract

Spinal metabotropic glutamate receptors (mGluRs) and opioid receptors are involved in the modulation of nociception. Although opioid receptor agonists are active in a postoperative pain, the effects of the agents on mGluRs have not been thoroughly investigated at the spinal level. The aim of this study was to clarify the role of spinal mGluRs to postoperative pain. In addition, the nature of pharmacological interaction between the mGluRs agents and morphine was determined. Catheters were inserted into the intrathecal space of male SD rats. For induction of postoperative pain, an incision was made in the plantar surface of the hindpaw. The pharmacologic characteristic for interaction was evaluated with fixed-dose analysis. None of the mGluRs agents applied intrathecally modified the withdrawal threshold in the incisional pain, while intrathecal morphine increased the withdrawal threshold in a dose-dependent manner. The fixed-dose analysis revealed that both mGlu1a antagonist (LY 367385) and group III mGluRs agonist (ACPT-III) increased the antinociceptive action of morphine. But, other mGluRs agents did not affect the antinociception of morphine. These results suggest that mGluRs may not play a modulatory role in the processing of postoperative pain directly at the spinal level. But blocking the mGlu1a receptor and activating group III mGluRs in the spinal cord may indirectly contribute to the potentiation of morphine's antinociception. Thus, spinal combination of morphine with either mGlu1a antagonist or group III mGluRs agonist may be useful in the management of the postoperative pain.