| First Author | Lu J | Year | 2018 |
| Journal | Neuropharmacology | Volume | 133 |
| Pages | 224-232 | PubMed ID | 29407767 |
| Mgi Jnum | J:261337 | Mgi Id | MGI:6155320 |
| Doi | 10.1016/j.neuropharm.2018.01.041 | Citation | Lu J, et al. (2018) Involvement of glycine receptor alpha1 subunits in cannabinoid-induced analgesia. Neuropharmacology 133:224-232 |
| abstractText | Some cannabinoids have been shown to suppress chronic pain by targeting glycine receptors (GlyRs). Although cannabinoid potentiation of alpha3 GlyRs is thought to contribute to cannabinoid-induced analgesia, the role of cannabinoid potentiation of alpha1 GlyRs in cannabinoid suppression of chronic pain remains unclear. Here we report that dehydroxylcannabidiol (DH-CBD), a nonpsychoactive cannabinoid, significantly suppresses chronic inflammatory pain caused by noxious heat stimulation. This effect may involve spinal alpha1 GlyRs since the expression level of alpha1 subunits in the spinal cord is positively correlated with CFA-induced inflammatory pain and the GlyRs antagonist strychnine blocks the DH-CBD-induced analgesia. A point-mutation of S296A in TM3 of alpha1 GlyRs significantly inhibits DH-CBD potentiation of glycine currents (IGly) in HEK-293cells and neurons in lamina I-II of spinal cord slices. To explore the in vivo consequence of DH-CBD potentiation of alpha1 GlyRs, we generated a GlyRalpha1(S296A) knock-in mouse line. We observed that DH-CBD-induced potentiation of IGly and analgesia for inflammatory pain was absent in GlyRalpha1(S296A) knock-in mice. These findings suggest that spinal alpha1 GlyR is a potential target for cannabinoid analgesia in chronic inflammatory pain. |
