Glycine receptors: a new therapeutic target in pain pathways.

Although glycine receptor Cl- channels (GlyRs) have long been known to mediate inhibitory neurotransmission onto spinal nociceptive neurons, their therapeutic potential for peripheral analgesia has received little attention. However, it has been shown that alpha3-subunit-containing GlyRs are concentrated into regions of the spinal cord dorsal horn where nociceptive afferents terminate. Furthermore, inflammatory mediators specifically inhibit alpha3-containing GlyRs, and deletion of the murine alpha3 gene confers insensitivity to chronic inflammatory pain. This strongly implicates GlyRs in the inflammation-mediated disinhibition of centrally projecting nociceptive neurons. Future therapies aimed at specifically increasing current flux through alpha3-containing GlyRs may prove effective in providing analgesia.