GlyR$\alpha3$: An Essential Target for Spinal$PGE_2-Mediated$Inflammatory Pain Sensitization

Prostaglandin E2(PGE2) is a crucial mediator of inflammatory pain sensitization. Here, we demonstrate that inhibition of a specific glycine receptor subtype ($GlyR \alpha3$) by$PGE_2-induced$receptor phosphorylation underlies central inflammatory pain sensitization. We show that GlyR$\alpha3$is distinctly expressed in superficial layers of the spinal cord dorsal horn. Mice deficient in GlyR$\alpha3$not only lack the inhibition of glycinergic neurotransmission by PGE2seen in wildtype mice but also show a reduction in pain sensitization induced by spinal PGE2injection or peripheral inflammation. Thus, GlyR$\alpha3$may provide a previously unrecognized molecular target in pain therapy.