Activation of peripheral group III metabotropic glutamate receptors suppressed formalin-induced nociception.

Intraplantar injection of formalin produces persistent spontaneous nociception and hyperalgesia. The underlying mechanism, however, remains unclear. The present study was, therefore, designed to determine the roles of peripheral group III metabotropic glutamate receptors (mGluRs) in formalin-evoked spontaneous nociception. Pre-treatment with intraplantar injections of L-serine-O-phosphate (L-SOP), a group III mGluRs agonist, significantly inhibited formalin-induced nociceptive behaviours and decreased Fos production in the spinal dorsal horn. The inhibitory effects of L-SOP were abolished completely by pre-treatment with the group III mGluR antagonist (RS)-a-methylserine-O-phosphate (M-SOP). These data suggest that the activation of group III mGluRs in the periphery may play a differential role in formalin-induced nociception. In addition, L-SOP decreased the formalin-induced upregulation of tumour necrosis factor-α (TNF-α) as well as interleukine-1β (IL-1β) expression in the spinal cord, suggesting that activation of peripheral group III mGluRs reduces formalin-induced nociception through inhibition of the pro-inflammatory cytokines in the spinal cord. Therefore, the agonists acting peripheral group III mGluRs possess therapeutic effectiveness in chronic pain.