Antihyperalgesic effect by herpes vector-mediated knockdown of Na v 1.7 sodium channels after skin incision

Postincisional hyperalgesia and allodynia play an important role in perioperative medicine. Na V 1.7 sodium channel has proven to be a key player in several pain states, including acute, inflammatory, and neuropathic pain. This study investigated the effects of silencing Na V 1.7 through Herpes-based gene therapy with an antisense transcript on pain states after incision of the skin in rodents. Seventy-six Balb/C mice were subdivided into six groups and were treated with no virus, control virus, or Na V 1.7 antisense vector before lateral hindpaw skin incision or sham procedure. All mice were tested for mechanical allodynia, cold allodynia, and thermal hyperalgesia. For time series analysis, a two-way analysis of variance with post-hoc Bonferroni testing was used. After incision mice developed significant hypersensitivity to mechanical, cold, and heat stimuli. The Na V 1.7 antisense vector blocked the hypersensitivity to mechanical, cold, and heat stimuli that was normally observed 24 and 48 h after incision. We demonstrated that a gene therapy-based Na V 1.7 knockdown affects postincisional hyperalgesia and allodynia. The data provide evidence that the incision model leads to periwound hypersensitivity after incision and that application of the Na V 1.7 antisense virus prevents this sensitization. This then, in turn, provides presumptive support to the hypothesis that overexpression of the Na V 1.7 channel is an important mechanism underlying hyperalgesia and allodynia following skin incision.