title: Role of the TREK2 potassium channel in cold and warm thermosensation and in pain perception.
abstract: Two-pore domain background K(+) channels (K2p or KCNK) produce hyperpolarizing currents that control cell membrane polarity and neuronal excitability throughout the nervous system. The TREK2 channel as well as the related TREK1 and TRAAK channels are mechanical-, thermal- and lipid-gated channels that share many regulatory properties. TREK2 is one of the major background channels expressed in rodent nociceptive neurons of the dorsal root ganglia that innervate the skin and deep body tissues, but its role in somatosensory perception and nociception has remained poorly understood. We now report that TREK2 is a regulatory channel that controls the perception of non aversive warm, between 40°C and 46°C, and moderate ambient cool temperatures, between 20°C and 25°C, in mice. TREK2 controls the firing activity of peripheral sensory C-fibers in response to changes in temperature. The role of TREK2 in thermosensation is different from that of TREK1 and TRAAK channels; rather, TREK2, TREK1, and TRAAK channels appear to have complementary roles in thermosensation. TREK2 is also involved in mechanical pain perception and in osmotic pain after sensitization by prostaglandin E2. TREK2 is involved in the cold allodynia that characterizes the neuropathy commonly associated with treatments with the anticancer drug oxaliplatin. These results suggest that positive modulation of the TREK2 channel may have beneficial analgesic effects in these neuropathic conditions.
authors.affiliation: Clermont Université, Université d'Auvergne, Pharmacologie fondamentale et clinique de la douleur, Clermont-Ferrand, France Inserm, U 1107, Neuro-Dol, Clermont-Ferrand, France CHU Clermont-Ferrand, Service de pharmacologie, Clermont-Ferrand, France Université de Nice Sophia Antipolis, Nice, France CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Valbonne, France Universités de Montpellier 1 et 2, Montpellier, France CNRS, Institut de Génomique Fonctionnelle, UMR-5203, Département de Physiologie, Montpellier, France LabEx Ion Channel Science and Therapeutics, Valbonne, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Pereira
authors.forename: Jérôme
authors.initials: J
authors.lastname: Busserolles
authors.forename: Marine
authors.initials: M
authors.lastname: Christin
authors.forename: Maïly
authors.initials: M
authors.lastname: Devilliers
authors.forename: Laura
authors.initials: L
authors.lastname: Poupon
authors.forename: Wassim
authors.initials: W
authors.lastname: Legha
authors.forename: Abdelkrim
authors.initials: A
authors.lastname: Alloui
authors.forename: Youssef
authors.initials: Y
authors.lastname: Aissouni
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bourinet
authors.forename: Florian
authors.initials: F
authors.lastname: Lesage
authors.forename: Alain
authors.initials: A
authors.lastname: Eschalier
authors.forename: Michel
authors.initials: M
authors.lastname: Lazdunski
authors.forename: Jacques
authors.initials: J
authors.lastname: Noël
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006930:Hyperalgesia; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology; D009944:Organoplatinum Compounds / Q000633:toxicity; D000077150:Oxaliplatin; D010147:Pain Measurement; D058748:Pain Perception / Q000187:drug effects / Q000502:physiology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology / Q000523:psychology*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000503:physiopathology*; D010812:Physical Stimulation; D015221:Potassium Channels / Q000235:genetics; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D013697:Thermosensing / Q000187:drug effects / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C503445:Kcnk10 protein, mouse; C503433:Kcnk4 protein, mouse; D009944:Organoplatinum Compounds; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; D000077150:Oxaliplatin
keywords: Background potassium channel; Mechanosensation; Oxaliplatin chemotherapy-induced neuropathy; TREK2; Thermosensation