Novel G protein-coupled receptors as pain targets.
G protein-coupled receptors (GPCRs) and their ligands play a number of important roles in the modulation of acute and chronic pain. Indeed, opioid and cannabinoid ligands are of established therapeutic value for pain management, and further exploitation of the specific GPCR subtypes (delta-opioid, CB1 and CB2) for these ligands may yield more selective, potent analgesics with favorable side effects. More recent identification of a number of other GPCRs involved in pain pathways (eg, sensory neuron specific receptors) and selective ligands that modulate pain transmission, has highlighted further therapeutic opportunities. A further challenge to understanding pain modulation and an additional dimension for targeting analgesia is the discovery of GPCR heteromerization and accessory and regulatory proteins, such as regulator of G protein-signaling proteins, involved in expression and regulation of GPCR.
Ahmad
Sultan
S
AstraZeneca Research & Development Montreal, 7171 Frederick Banting St, Montreal H4S 1Z9, Canada.
Dray
Andy
A
D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D044183:Receptor, Parathyroid Hormone, Type 2 / Q000187:drug effects / Q000502:physiology; D043882:Receptors, Cannabinoid / Q000187:drug effects / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D044088:Receptors, Galanin / Q000187:drug effects / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000502:physiology
D000700:Analgesics; D008024:Ligands; D008565:Membrane Proteins; D044183:Receptor, Parathyroid Hormone, Type 2; D043882:Receptors, Cannabinoid; D043562:Receptors, G-Protein-Coupled; D044088:Receptors, Galanin; D017981:Receptors, Neurotransmitter; D017465:Receptors, Opioid, delta; C082444:neuromedin U receptor