Potentiation of morphine antiallodynic efficacy by ACPT-III, a group III metabotropic glutamate receptor agonist, in rat spinal nerve ligation-induced neuropathic pain.
Despite the importance of spinal metabotropic glutamate receptors (mGluRs) and opioid receptors in nociceptive processing, the roles of these receptors in the modulation of neuropathic pain at the spinal level have not been thoroughly investigated. The purpose of this study was to investigate the effects of spinal mGluR agents and opioids (morphine) on neuropathic pain. Male Sprague-Dawley rats underwent L5 and L6 spinal nerve ligation to induce neuropathic pain and intrathecal catheterization for drug administration. A paw-withdrawal threshold to mechanical stimulus was measured using the "up and down" method. When administered intrathecally, neither Group I mGluR antagonists nor Group II or III agonists modified the withdrawal threshold after spinal nerve ligation. Intrathecal administration of morphine dose-dependently increased the withdrawal threshold. Whereas ACPT-III, a Group III mGluR agonist, enhanced the antiallodynic action of morphine, other mGluR agents did not. Collectively, mGluRs may not directly modulate the processing of spinal nerve ligation-induced neuropathic pain at the spinal level. However, Group III mGluR agonists in the spinal cord may indirectly contribute to the potentiation of morphine antiallodynia, indicating that these agonists might be used as adjuvants for spinal morphine.
Lee
Hyung Gon
HG
Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, 8 Hakdong, Donggu, Gwangju 501-757, Republic of Korea.
Park
Sung Keun
SK
Yoon
Myung Ha
MH
D000700:Analgesics / Q000145:classification / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D018690:Excitatory Amino Acid Agonists / Q000145:classification / Q000494:pharmacology / Q000627:therapeutic use*; D008026:Ligation; D008297:Male; D009020:Morphine / Q000494:pharmacology / Q000627:therapeutic use*; D009437:Neuralgia / Q000188:drug therapy* / Q000473:pathology; D010146:Pain / Q000188:drug therapy / Q000473:pathology; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000502:physiology; D013127:Spinal Nerves / Q000187:drug effects / Q000293:injuries*; D016896:Treatment Outcome
C097299:4-aminopyrrolidine-2,4-dicarboxylic acid; D000700:Analgesics; D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; C102718:metabotropic glutamate receptor 3; D009020:Morphine; D011392:Proline