In Search of Analgesia: Emerging Poles of GPCRs in Pain

Current status and opportunities in GPCR targeting. A) Predicted proportions of human GPCRs by nervous system expression (90%) and orphan status (40%). Approximately one-third of all GPCR genes encode orphan receptors that are expressed in the CNS. The endogenous ligand(s) and physiological function(s) of these receptors remain to be discovered, representing enormous opportunities for drug development. B) Modulatory effects of GPCRs organized by family. The equal distribution of inhibitory, excitatory, and mixed functional families suggests an equal balance between pro- and anti-nociception.