Basimglurant, an mGluR5-Selective Negative Allosteric Modulator, Dose Not Reduce Pain but Alleviate Pain Related Anxiety-Like Behavior (P4.065)

Objective:This study investigated the effects of a single administration of basimglurant, a negative allosteric modulator (NAM) of metabotropic glutamate receptor 5 (mGluR5), on pain and related anxiety in neuropathic mice. Background:Despite high prevalence of anxiety accompanying with chronic pain, the mechanisms underlying pain-related anxiety are largely unknown. With its well-documented role in pain and emotion processing, the prefrontal cortex and amygdala may act as key players in pathogenesis of neuropathic pain-related anxiety. Methods/Results:The spared nerve injury (SNI) of the sciatic nerve induced, 7 days after surgery, thermal hyperalgesia and mechanical allodynia, decreased time in the centre of the open field test (OFT). Immunohistochemical studies and western blot showed mGluR5 expression increased in the amygdala while decreased in the prefrontal cortex in SNI mice. This was consist with previous work that abnormal inhibition of mPFC pyramidal cells and hyperactivity of amygdala output neurons in chronic pain model.In the behavioral studies, basimglurant (0.2-10mg/kg p.o.) had essentially no effect on pain induced by thermal stimuli on the lesioned side. However, basimglurant (0.3-1 mg/kg, p.o.) alleviated pain related anxiety-like beheavior, which examined using OFT. The activity patterns of the prefrontal cortex and amyadala were different after administration of basimglurant, because the effect of basimglurant was indeed mediated by mGluR5 expression. Conclusions:Our findings showed the effect of basimglurant on pain related anxiety-like beheavior but not pain sensation, which may provide novel insights into the role of mGluR5 in the regulation of anxiety caused by chronic pain. Study Supported by: Grants from the National Natural Science Foundation of China (No. 81371240) Disclosure: Dr. cai has nothing to disclose. Dr. wang has nothing to disclose. Dr. che has nothing to disclose. Dr. yang has nothing to disclose. Dr. wu has nothing to disclose.