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

摘要

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 μL,or the equivalent volume of normal saline,was administered by intrathecal injection into the L3-5 region of the spinal cord in the experimental and control groups,respectively.After 15 minutes,formalin (5%,50 μL) 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.