title: Opiates modulate thermosensation by internalizing cold receptor TRPM8.
abstract: Stimulation of μ-opioid receptors (OPRMs) brings powerful pain relief, but it also leads to the development of tolerance and addiction. Ensuing withdrawal in abstinent patients manifests itself with severe symptoms, including cold hyperalgesia, often preventing addicted patients from successfully completing the rehabilitation. Unsurprisingly, OPRMs have been a central point of many studies. Nonetheless, a satisfactory understanding of the pathways leading to distorted sensory responses during opiate administration and abstinence is far from complete. Here, we present a mechanism that leads to modulation by OPRMs of one of the sensory responses, thermosensation. Activation of OPRM1 leads to internalization of a cold-sensor TRPM8, which can be reversed by a follow-up treatment with the inverse OPRM agonist naloxone. Knockout of TRPM8 protein leads to a decrease in morphine-induced cold analgesia. The proposed pathway represents a universal mechanism that is probably shared by regulatory pathways modulating general pain sensation in response to opioid treatment.
authors.affiliation: Inserm U1003, Equipe Labellisee par la Ligue Nationale Contre le Cancer, Universite de Sciences et Technologies de Lille (USTL), 59655 Villeneuve d'Ascq, France.
authors.forename: George
authors.initials: G
authors.lastname: Shapovalov
authors.forename: Dimitra
authors.initials: D
authors.lastname: Gkika
authors.forename: Maily
authors.initials: M
authors.lastname: Devilliers
authors.forename: Artem
authors.initials: A
authors.lastname: Kondratskyi
authors.forename: Dmitri
authors.initials: D
authors.lastname: Gordienko
authors.forename: Jerome
authors.initials: J
authors.lastname: Busserolles
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bokhobza
authors.forename: Alain
authors.initials: A
authors.lastname: Eschalier
authors.forename: Roman
authors.initials: R
authors.lastname: Skryma
authors.forename: Natalia
authors.initials: N
authors.lastname: Prevarskaya
mesh_terms: D000818:Animals; D057809:HEK293 Cells; D006358:Hot Temperature; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D017450:Receptors, Opioid, mu; D050053:TRPM Cation Channels; C425966:TRPM8 protein, human; C492297:TRPM8 protein, mouse; C498947:Trpm8 protein, rat; D009270:Naloxone; D009020:Morphine