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-1ß (IL-1ß) 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.

[Effects of neurogenesis in the dentate gyrus (DG) of hippocampus on depression-like behaviors in WKY rats].

OBJECTIVE: To observe the effects of the neurogenesis in the dentate gyrus (DG) of the hippocampus on depression-like behaviors in adult Wistar Kyoto (WKY) rats. METHODS: There were three groups in total (n = 10): ① the control (Wistar) group: 9-week-old Wistar rats were treated with saline for 3 weeks (10 mg/kg, intragastric administration); ② the depression model (WKY) group: WKY rats of the same age, tested for depression-like behaviors, were as a rat model of depression, and were treated with saline for 3 weeks (10 mg/kg, intragastric administration); ③ the positive control (AMI+WKY) group: WKY rats of the same age were treated with amitriptyline for 3 weeks (10 mg/kg, intragastric administration). The neurogenesis in hippocampus was detected by immunofluorescence staining for Ki67 (a neuronal proliferation marker) and DCX (an immature neuronal marker). The depression-like behaviors were assessed by sucrose preference test (SPT), open field test (OFT) and forced swimming test (FST). RESULTS: ① When compared with Wistar rats, the number of Ki67+ cells and DCX+ cells of the DG in WKY rats were decreased by 33.0% (P＜0.01) and 39.2% (P＜0.01), respectively; amitriptyline treatment significantly increased the number of Ki67+cells and DCX+ cells in the DG by 43.8% (P＜0.01) and 46.7% (P＜0.01), respectively, as compared with WKY rats. ② When compared with control group, WKY rats showed a significant decrease in sucrose preference (P＜0.01), less total horizontal distance (P＜0.01) and less time entered the center field (P＜0.01) in the OFT, the immobility time in the FST was increased significantly (P＜0.01). Amitriptyline treatment significantly improved the depression-like behaviors in WKY rats. CONCLUSION: ① The proliferation and differentiation of hippocampal neural stem cells in adult WKY rats are significantly lower than those of Wistar rats, suggesting that the neurogenesis in adult WKY rats is impaired. ②Amelioration of impaired hippocampal neurogenesis can partially reverse the depression-like behaviors in adult WKY rats.