Deficiency in the function of inhibitory interneurons contributes to glutamate‐associated central sensitization through GABABR2‐SynCAM1 signaling in chronic migraine rats

The occurrence of pain has always been closely related to a break in the balance between excitatory and inhibitory systems, and the internal relationship between these two systems has not been studied in the pathogenesis of chronic migraine (CM). In this study, we explored how inhibitory interneurons specifically modulate the glutamate‐induced hyperexcitability in the periaqueductal gray (PAG) of CM rats. The CM model was established by repeated dural infusion of inflammatory soup (IS) in rats. Then, Baclofen, a gamma‐aminobutyric acid type B receptor (GABABR) agonist; CGP35348, a GABABR antagonist; H89, a protein kinase A (PKA) inhibitor; and 8‐Bromo‐cAMP, a PKA agonist, were applied by intraventricular injection to investigate the detailed CM mechanism. Our results showed that GABABR2 mRNA and protein levels were significantly downregulated (P