Modulation of pain transmission by G-protein-coupled receptors.
The heterotrimeric G-protein-coupled receptors (GPCR) represent the largest and most diverse family of cell surface receptors and proteins. GPCR are widely distributed in the peripheral and central nervous systems and are one of the most important therapeutic targets in pain medicine. GPCR are present on the plasma membrane of neurons and their terminals along the nociceptive pathways and are closely associated with the modulation of pain transmission. GPCR that can produce analgesia upon activation include opioid, cannabinoid, alpha2-adrenergic, muscarinic acetylcholine, gamma-aminobutyric acidB (GABAB), groups II and III metabotropic glutamate, and somatostatin receptors. Recent studies have led to a better understanding of the role of these GPCR in the regulation of pain transmission. Here, we review the current knowledge about the cellular and molecular mechanisms that underlie the analgesic actions of GPCR agonists, with a focus on their effects on ion channels expressed on nociceptive sensory neurons and on synaptic transmission at the spinal cord level.
Pan
Hui-Lin
HL
Department of Anesthesiology and Pain Medicine, The University of Texas M.D. Anderson Cancer Center, Program in Neuroscience, The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77225, United States. huilinpan@mdanderson.org
Wu
Zi-Zhen
ZZ
Zhou
Hong-Yi
HY
Chen
Shao-Rui
SR
Zhang
Hong-Mei
HM
Li
De-Pei
DP
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000503:physiopathology*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism*; D009435:Synaptic Transmission
D000700:Analgesics; D007473:Ion Channels; D043562:Receptors, G-Protein-Coupled