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Glucagon-like peptide-1 receptor agonist attenuates diabetic neuropathic pain via inhibition of NOD-like receptor protein 3 inflammasome in brain microglia

Published:February 27, 2022DOI:https://doi.org/10.1016/j.diabres.2022.109806

      Highlights

      • Brain microglial activation in DNP rats was observed by PET/CT with [18F]-DPA-714 as a dedicated radiotracer.
      • GLP-1RA significantly alleviated mechanical and thermal pain in rats with DNP via intracerebroventricular injection.
      • GLP-1RA suppressed the activation of NLRP3 inflammasome in microglia.

      Abstract

      Aims

      We aimed to explore the evidence of brain microglia activation in diabetic neuropathic pain (DNP) and the effect and mechanism of glucagon-like peptide-1 receptor agonist (GLP-RA) on DNP via brain microglia.

      Methods

      Brain microglia activation was observed in DNP rats by positron emission tomography/computed tomography. The behavior of neuropathic pain was assessed in DNP rats after intracerebroventricular administration of GLP-1RA or microglial inhibitor minocycline. RNA sequencing was performed to explore the target of GLP-1RA on brain microglia. NOD-like receptor protein 3 (NLRP3) expression in brain microglia was evaluated in mentioned-above DNP rats, and the activation of NLRP3 inflammasome was analyzed in microglia treated with GLP-1RA.

      Results

      Microglia were activated in the cortex and thalamus of DNP rats. The thermal and mechanical allodynia were alleviated in DNP rats via intracerebroventricular administration of GLP-1RA or minocycline. And the activation of brain microglia was attenuated in DNP rats by intracerebroventricular administration of GLP-1RA. The expression of NLRP3 in brain microglia, which was found by RNA sequencing, was reduced in DNP rats by administration of GLP-1RA. Furthermore, GLP-1RA attenuated NLRP3 inflammasome activation in microglia triggered by LPS.

      Conclusion

      GLP-1RA could alleviate DNP, possibly mediated by the suppression of brain microglia NLRP3 inflammasome activation.

      Keywords

      Abbreviations:

      DNP (Diabetic neuropathic pain), GLP-1RA (Glucagon-like peptide-1 receptor agonist), NLRP3 (NOD-like receptor protein 3)
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