GlyR α3:: An essential target for spinal PGE2-mediated inflammatory pain sensitization

Prostaglandin E-2 (PGE(2)) 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 PGE(2) seen in wildtype mice but also show a reduction in pain sensitization induced by spinal PGE(2) injection or peripheral inflammation. Thus, GlyR alpha3 may provide a previously unrecognized molecular target in pain therapy.