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Publication : Opiates modulate thermosensation by internalizing cold receptor TRPM8.

First Author  Shapovalov G Year  2013
Journal  Cell Rep Volume  4
Issue  3 Pages  504-15
PubMed ID  23911290 Mgi Jnum  J:201902
Mgi Id  MGI:5516146 Doi  10.1016/j.celrep.2013.07.002
Citation  Shapovalov G, et al. (2013) Opiates modulate thermosensation by internalizing cold receptor TRPM8. Cell Rep 4(3):504-15
abstractText  Stimulation of mu-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.
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