Year: 2013
Type: article
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.
Source: Cell Reports
Institutions: Inserm, Université de Lille, La Ligue Contre le Cancer, Laboratoire d'Excellence Canaux Ioniques d'Intérêt Thérapeutique, Université Clermont Auvergne, Physiopathologie et pharmacologie de la douleur et de la migraine, Université de Clermont I, Centre Hospitalier Universitaire de Clermont-Ferrand
Language: English
Topic: Ion Channels and Receptors
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funder: Agence Nationale de la Recherche
OpenAlex ID: W1973194313