Methyl cinnamate alleviated CCI-induced upregualtion of spinal AMPA receptors and pain hypersensitivity by targeting AMPK

Various studies proved spinal AMPA receptors were involved in the formation of neuropathic pain. In this study, we investigated the effect of methyl cinnamate (MC), a flavoring agent widely used in food and commodity industry, on CCI-induced upregulation of spinal AMPARs and pain hypersensitive behaviors. Results indicated that MC treatment dosage-dependently inhibited CCI-induced mechanical and thermal hypersensitivity. To further investigate the effect of MC after the formation of neuropathic pain, MC at the dosage of 100 mg/kg was administrated on day 7-14 on CCI rats. Results showed that MC treatment for seven days alleviated CCI-induced pain hypersensitivity after the formation of neuropathic pain. MC treatment reversed CCI-induced upregulation of GluR2, GluR3 and phosphorylation of GluR1. Further, MC dosage-dependently alleviated CCI-induced activation of mTOR and the downstream p70s6k. MC dosage-dependently induced activation of AMPK. All the MC-induced effects in CCI rats were completely reversed by Compound C, a AMPK inhibitor. These results meant MC treatment mitigated CCI-induced upregualtion of spinal AMPA receptors and pain hypersensitive behaviors through actviation of AMPK.