| First Author | Dembla S | Year | 2017 |
| Journal | Elife | Volume | 6 |
| PubMed ID | 28826482 | Mgi Jnum | J:258922 |
| Mgi Id | MGI:6140968 | Doi | 10.7554/eLife.26280 |
| Citation | Dembla S, et al. (2017) Anti-nociceptive action of peripheral mu-opioid receptors by G-beta-gamma protein-mediated inhibition of TRPM3 channels. Elife 6:e26280 |
| abstractText | Opioids, agonists of micro-opioid receptors (microORs), are the strongest pain killers clinically available. Their action includes a strong central component, which also causes important adverse effects. However, microORs are also found on the peripheral endings of nociceptors and their activation there produces meaningful analgesia. The cellular mechanisms downstream of peripheral microORs 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 microOR 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 Gbetagamma proteins, which form a complex with TRPM3. Accordingly, activation of peripheral microORs in vivo strongly attenuates TRPM3-dependent pain. Our data establish TRPM3 inhibition as important consequence of peripheral microOR activation indicating that pharmacologically antagonizing TRPM3 may be a useful analgesic strategy. |
