Metabotropic glutamate receptor 5 regulates synaptic plasticity in a chronic migraine rat model through the PKC/NR2B signal

Abstract

Background The mechanism of chronic migraine (CM) is complex, central sensitization is considered as one of the pathological mechanism. Synaptic plasticity is the basis of central sensitization. Metabotropic glutamate receptor 5 (mGluR5) plays a vital role in the synaptic plasticity of the central nervous system. However, whether mGluR5 can promote the central sensitization by regulating synaptic plasticity in CM is unknown. Methods Male Wistar rats were used to establish a CM rat model, and the expression of mGluR5 mRNA and protein were detected by qRT-PCR and western blot. The allodynia was assessed by mechanical and thermal thresholds, and central sensitization was assessed by expression of the phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) at Serine 133(pCREB-S133) and c-Fos. The synaptic-associated protein postsynaptic density protein 95 (PSD), synaptophysin (Syp), and synaptophysin-1(Syt-1), synaptic ultrastructure, and dendritic spines were detected to explore synaptic plasticity. The expression of PKC, total NR2B(tNR2B), and phosphorylation of NR2B at Tyr1472(pNR2B-Y1472) were detected by western blot. Results We found that the expression of mGluR5 was upregulated in CM rats. Downregulated the mGluR5 with MPEP alleviated the allodynia and reduced the expression of CGRP, pCREB-S133, c-Fos, PSD, Syp and Syt-1 and synaptic transmission. Moreover, the administration of MPEP inhibited the upregulation of PKC and pNR2B-Y1472. Conclusions These results indicate that mGluR5 contributes to central sensitization by regulating synaptic plasticity in CM through the PKC/NR2B signal, which suggests that mGluR5 may be a potential therapeutic candidate for CM.

Rostral Anterior Cingulate Cortex–Ventrolateral Periaqueductal Gray Circuit Underlies Electroacupuncture to Alleviate Hyperalgesia but Not Anxiety-Like Behaviors in Mice With Spared Nerve Injury

“…In this study, we found that specific activation of the rACC Glu -vlPAG pathway could lead to hyperalgesia and anxiety-like behaviors in sham mice in relation to changes in the synaptic plasticity of the glutamatergic neurons in the rACC output. Research has shown that changes in synaptic plasticity are closely related to the formation of pain, and synaptic plasticity is also the basis of central sensitization ( Niu et al, 2020 ). Meanwhile, other researchers have pointed out that an increased expression of long-term potentiation in the rACC promotes pain-related anxiety through glutamate transmitter release ( Bliss et al, 2016 ).…”

Examining mGlu5 Receptor Availability as a Predictor of Vulnerability to PTSD: An [18F]FPEB and PET Study in Male and Female Rats

“…43 Therefore, future investigations into whether interactions between estrogen and mGlu5 could influence resilience and vulnerability in the SEFL paradigm would be of merit. Second, given mGlu5's involvement in nociception and chronic pain, [44][45][46] it is possible that the painful nature of footshocks is a necessary mediator for a relationship between higher mGlu5 availability and SEFL susceptibility, and that is related to differences in pain processing. This potential confound would fit in with clinical observations suggesting overlapping molecular mechanisms mediating chronic pain syndromes and stress-related psychiatric disorders, including PTSD.…”

170. Age-Dependent Effects of Tobacco Smoke and Nicotine on Cognition and the Brain: A Systematic Review of the Human and Animal Literature Comparing Adolescents and Adults

“…The actions of glutamate are mediated by metabotropic (mGluR) and ionotropic (iGluR) glutamate receptors (Kew and Kemp, 2005). In particular, the mGluR5 receptor regulates synaptic plasticity of several mesocorticolimbic regions (Niu et al, 2020). Drug-evoked changes in synaptic plasticity have frequently been reported in regions including the nucleus accumbens (NAc) and are suggested to contribute to the aetiology of addiction (Lüscher and Malenka, 2011).…”