Description
- Nav1.8 sodium channels, encoded by SCN10A, are predominantly expressed in the sensory neurons located in the dorsal root ganglion (DRG) and play an important role in human pain. In animal models of chronic pain, Nav1.8 is also verified to be involved, suggesting that Nav1.8 may be a potential target for treatment of chronic pain.
- Gene editing strategy: The bacterial artificial chromosome (BAC) clone CH17-178G5 containing the whole human SCN10A genome sequence was randomly inserted into rat genome in B-Tg(hSCN10A),Scn10a KO rats. The exons 2-28 of rat Scn10a that encode the full-length protein were knocked out in B-Tg(hSCN10A),Scn10a KO rats.
- mRNA expression analysis: Human SCN10A mRNA was detectable only in B-Tg(hSCN10A),Scn10a KO rats but not in wild-type SD rats.
- In vivo efficacy of VX-548 in postoperative pain model: VX-548 at 10 mg/kg significantly alleviated postoperative pain with an analgesic effect lasting up to 2 h in B-Tg(hSCN10A),Scn10a KO rats, but not in wild-type SD rats.
- Application: This product is used for the efficacy research and safety evaluation of analgesic drugs.
Targeting Strategy
Gene targeting strategy for B-Tg(hSCN10A),Scn10a KO rats.
The bacterial artificial chromosome (BAC) clone CH17-178G5 containing the whole human SCN10A genome sequence was randomly inserted into rat genome in B-Tg(hSCN10A),Scn10a KO rats.
The exons 2-28 of rat Scn10a that encode the full-length protein were knocked out in B-Tg(hSCN10A),Scn10a KO rats.
In vivo Efficacy of VX-548 in Postoperative Pain Model
Postoperative pain modeling and analgesic effects of VX-548 in wild-type SD rats and B-Tg(hSCN10A),Scn10a KO rats. In wild-type SD rats and B-Tg(hSCN10A),Scn10a KO rats, plantar incision markedly reduced mechanical pain thresholds. In wild-type SD rats, VX-548 at 60 mpk significantly alleviated postoperative pain with an analgesic effect lasting up to 2 h, whereas 10 mpk showed no effect. In B-Tg(hSCN10A),Scn10a KO rats, VX-548 at 10 mpk significantly alleviated postoperative pain with an analgesic effect lasting up to 2 h. B-Tg(hSCN10A),Scn10a KO rats provide a powerful preclinical model for in vivo evaluation of the efficacy of targeted human SCN10A analgesic drugs. (A) Grouping and Treatment. (B) The schematic diagram of postoperative pain modeling. (C) Analgesic effect of VX-548. *P < 0.05, **P < 0.01, ***P < 0.001.
* When publishing results obtained using this animal model, please acknowledge the source as follows: The animal model [B-Tg(hSCN10A),Scn10a KO rats] (Cat# 114048) was purchased from Biocytogen.
