Glycine Receptors in Spinal Nociceptive Control-An Update

Diminished inhibitory control of spinal nociception is one of the major culprits of chronic pain states. Restoring proper synaptic inhibition is a well-established rational therapeutic approach explored by several pharmaceutical companies. A particular challenge arises from the need for site-specific intervention to avoid deleterious side effects such as sedation, addiction, or impaired motor control, which would arise from wide-range facilitation of inhibition. Specific targeting of glycinergic inhibition, which dominates in the spinal cord and parts of the hindbrain, may help reduce these side effects. Selective targeting of the alpha 3 subtype of glycine receptors (GlyRs), which is highly enriched in the superficial layers of the spinal dorsal horn, a key site of nociceptive processing, may help to further narrow down pharmacological intervention on the nociceptive system and increase tolerability. This review provides an update on the physiological properties and functions of alpha 3 subtype GlyRs and on the present state of related drug discovery programs.

Automated summary

Restoring proper synaptic inhibition in the spinal cord, particularly through targeting the alpha 3 subtype of glycine receptors, may help reduce deleterious side effects and increase tolerability in chronic pain states. This review provides an update on the physiological properties and functions of alpha 3 subtype GlyRs and related drug discovery programs.