Metabotropic Glutamate Receptor 5 in the Dysgranular Zone of Primary Somatosensory Cortex Mediates Neuropathic Pain in Rats

The primary somatosensory cortex (S1) plays a key role in the discrimination of somatic sensations. Among subdivisions in S1, the dysgranular zone of rodent S1 (S1DZ) is homologous to Brodmann's area 3a of primate S1, which is involved in the processing of noxious signals from the body. However, molecular changes in this region and their role in the pathological pain state have never been studied. In this study, we identified molecular alteration of the S1DZ in a rat model of neuropathic pain induced by right L5 spinal nerve ligation (SNL) surgery and investigated its functional role in pain symptoms. Brain images acquired from SNL group and control group in our previous study were analyzed, and behaviors were measured using the von Frey test, acetone test, and conditioned place preference test. We found that metabotropic glutamate receptor 5 (mGluR5) levels were significantly upregulated in the S1DZ contralateral to the nerve injury in the SNL group compared to the sham group. Pharmacological deactivation of mGluR5 in S1DZ ameliorated symptoms of neuropathic allodynia, which was shown by a significant increase in the mechanical paw withdrawal threshold and a decrease in the behavioral response to cold stimuli. We further confirmed that this treatment induced relief from the tonic-aversive state of chronic neuropathic pain, as a place preference memory associated with the treatment-paired chamber was formed in rats with neuropathic pain. Our data provide evidence that mGluR5 in the S1DZ is involved in the manifestation of abnormal pain sensations in the neuropathic pain state.