Antinociceptive synergistic effect of spinal mGluR2/3 antagonist and glial cells inhibitor on peripheral inflammation-induced mechanical hypersensitivity

• Published in: Brain research bulletin Vol. 79; no. 3; pp. 219 - 223
• Main Authors: Zhang, Ting, Zhang, Jing, Shi, Juan, Feng, Yupeng, Sun, Zhong Sheng, Li, Huili
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.05.2009
• Subjects: Amino Acids - pharmacology; Analgesics - pharmacology; Animals; Citrates - pharmacology; Complete Freund's adjuvant; Dose-Response Relationship, Drug; Freund's Adjuvant - administration & dosage; Glial cell; Hyperesthesia - physiopathology; Inflammation - physiopathology; Male; Mechanical allodynia; Metabotropic glutamate receptor 2/3; Neuroglia - metabolism; Neurology; Pain - drug therapy; Pain - physiopathology; Proline - analogs & derivatives; Proline - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Metabotropic Glutamate - antagonists & inhibitors; Receptors, Metabotropic Glutamate - genetics; Receptors, Metabotropic Glutamate - physiology; Spinal cord; Spinal Cord - metabolism; Synergistic interaction; Xanthenes - pharmacology; Glial cell; Spinal cord; Metabotropic glutamate receptor 2/3; Complete Freund's adjuvant; Synergistic interaction; Mechanical allodynia
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/j.brainresbull.2009.01.009

Abstract Metabotropic glutamate receptor (mGluR) 2/3 is distributed in neurons and glial cells in many regions of the nervous system, but its role in nociceptive processing is unclear. In this study, we examined the mRNA expressions of mGluR2 and mGluR3 , by real-time RT-PCR, in the spinal cord. We further investigated the possible involvement of mGluR2/3 and mechanisms underlying peripheral inflammatory pain induced by subcutaneous complete Freund's adjuvant (CFA) injection. We demonstrate that compared to the controls, the mRNA expression levels of mGluR2 and mGluR3 were significantly higher 4 h after CFA injection. Functionally, blocking mGluR2/3 by their antagonist (2S)-2-amino-2-[(1S, 2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495) alleviated the CFA-induced mechanical allodynia and the inhibitory effects were reversed by mGluR2/3 agonist (2R, 4R)-4-aminopyrrolidine-2,4-dicarboxylate ((2R, 4R)-APDC). In addition, a glial metabolism inhibitor dl -fluorocitric acid barium salt (fluorocitric acid) also inhibited the CFA-induced mechanical allodynia in a dose-dependent manner. Remarkably, simultaneous inhibition of mGluR2/3 and glial metabolism had synergistic effects. The co-administration of LY341495 and fluorocitric acid with minimal dosages produced significant more inhibition than the additive effects by the individual inhibitor alone. In summary, our data suggest that spinal mGluR2/3 contributes to the generation of mechanical allodynia induced by peripheral inflammation. We also suggest that involvement of mGluR2/3 in the communication between glial cells and neurons takes part in the processing of nociceptive information.