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Retrograde transport of endoneurially injected botulinum toxin into mouse sciatic nerve

Abstract

Recent work has shown that Botulinum toxins (BoNT) are taken up and transported in sensory nerve to cerebral spinal terminals, where they will cleave synaptic proteins (SNARES) and block hyperalgesic states with little change in motor function We sought i) to determine if such transport occurred after endoneurial delivery in the sciatic nerve. If such uptake occurred, we hypothesized that there would be a significant antihyperalgesic effect and SNARE cleavage at doses lower than those required after intraplantar delivery. We examined the BoNT-B serotype, which cleaves VAMP (vesicle associated membrane protein). To test this hypothesis, 1μL of saline, 0.05U, 0.1U, 0.5U, or 1.0U BoNT-B was injected into the sciatic nerves of isoflurane anesthetized C57Bl/6 male mice. Pain behavior was assessed by the counting of paw flinching initiated by unilateral intraplantar injection of formalin (20 μL/2% formalin). This study has shown that mice injected unilaterally endoneurially with 0.1U BoNT-B showed significantly reduced intraplantar formalin-induced flinching behavior as compared to saline animals. Mice that received 0.05U, 0.5U, or 1.0U BoNT-B did not have significantly different flinching behavior compared to saline animals. In previous work, intraplantar BoNT B produced comparable effects but at 10x higher doses. Ipsilateral and contralateral hind paw thermal escape latencies were not significantly different among any of the groups. Mice injected with saline, 0.5U, and 1.0U BoNT-B exhibited motor impairment of the ipsilateral hind limb. Western blotting to detect VAMP1/2 levels in the ipsilateral and contralateral DRG of saline and BoNT injected mice were not successful due to poor tissue yield. These data suggest that intrasciatic injection of BoNT may produce a potent effect upon pain behavior at doses lower than those required if given by intraplantar delivery.

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