TY - JOUR TI - Anti-nociceptive action of peripheral mu-opioid receptors by G-beta-gamma protein-mediated inhibition of TRPM3 channels AU - Dembla, Sandeep AU - Behrendt, Marc AU - Mohr, Florian AU - Goecke, Christian AU - Sondermann, Julia AU - Schneider, Franziska M AU - Schmidt, Marlene AU - Stab, Julia AU - Enzeroth, Raissa AU - Leitner, Michael G AU - Nuñez-Badinez, Paulina AU - Schwenk, Jochen AU - Nürnberg, Bernd AU - Cohen, Alejandro AU - Philipp, Stephan E AU - Greffrath, Wolfgang AU - Bünemann, Moritz AU - Oliver, Dominik AU - Zakharian, Eleonora AU - Schmidt, Manuela AU - Oberwinkler, Johannes A2 - Swartz, Kenton J VL - 6 PY - 2017 DA - 2017/08/15 SP - e26280 C1 - eLife 2017;6:e26280 DO - 10.7554/eLife.26280 UR - https://doi.org/10.7554/eLife.26280 AB - Opioids, agonists of µ-opioid receptors (µORs), are the strongest pain killers clinically available. Their action includes a strong central component, which also causes important adverse effects. However, µORs are also found on the peripheral endings of nociceptors and their activation there produces meaningful analgesia. The cellular mechanisms downstream of peripheral µORs are not well understood. Here, we show in neurons of murine dorsal root ganglia that pro-nociceptive TRPM3 channels, present in the peripheral parts of nociceptors, are strongly inhibited by µOR activation, much more than other TRP channels in the same compartment, like TRPV1 and TRPA1. Inhibition of TRPM3 channels occurs via a short signaling cascade involving Gβγ proteins, which form a complex with TRPM3. Accordingly, activation of peripheral µORs in vivo strongly attenuates TRPM3-dependent pain. Our data establish TRPM3 inhibition as important consequence of peripheral µOR activation indicating that pharmacologically antagonizing TRPM3 may be a useful analgesic strategy. KW - TRPM3 KW - MOP KW - peripheral opioid receptors KW - G-protein KW - pain KW - analgesia JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -