Involvement of group III metabotropic glutamate receptors in the modulation of spinal nociceptive signals

BACKGROUND: Previous morphological studies have demonstrated that group III metabotropic glutamate receptors (mGluRs) are commonly found in nociceptive pathways, particularly in the terminals of primary afferent fibers in the spinal dorsal horn. OBJECTIVE: To investigate the role of group III mGluRs in a rat model of spinal nociception by intrathecal administration of a selective agonist, L-Serine-O-phosphate (L-SOP). DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment. The study was performed at the Department of Physiology and Neurobiology, Shanxi Medical University, between March 2007 and May 2008. MATERIALS: L-SOP of group III mGluRs (Tocris Cookson Ltd, UK), formalin (Sigma, USA), rabbit anti-c-Fos polyclonal antibody and biotin-labeled goat anti-rabbit IgG (Cell Signaling Technology, USA) were used in this study. METHODS: A total of 26 healthy Wistar rats, aged 1 month and weighing 100-120 g, were subjected to intrathecal catheter implantation. After 5-8 days, 10 rats were selected according to experimental requirements. L-SOP 250 nmol in 10 mu L, or the equivalent volume of normal saline, was administered by intrathecal injection into the L-3.5 region of the spinal cord in the experimental and control groups, respectively. After 15 minutes, formalin (5%, 50 mu L) was subcutaneously injected into the plantar of the left hindpaw of each rat to establish formalin-induced pain models. MAIN OUTCOME MEASURES: Nociceptive behavioral responses and immunohistochemical examination of Fos expression. RESULTS: Intrathecal injection of L-SOP significantly attenuated the second phase nociceptive response compared with the control group (P < 0.05), and Fos expression in the spinal dorsal horn was significantly decreased along with the number of Fos-like immunoreactive neurons (P < 0.05). CONCLUSION: Group III mGluRs are involved in the modulation of nociceptive signals, and their activation suppresses the transmission of nociceptive signals.