The effect of recombinant botulinum neurotoxin A on neuropathic pain in the spared nerve injury mouse model.

Neuropathic pain following traumatic nerve injury is a disabling chronic pain disorder characterized by sensory abnormalities such as mechanical allodynia. Botulinum neurotoxin type A (BoNT/A) has shown analgesic properties in a range of clinical pain conditions and in animal models. Here, we investigated analgesic efficacy of recombinant BoNT/A1 (rBoNT/A1; IPN10260) in the spared nerve injury (SNI) mouse model of neuropathic pain. Potential tissue site and mechanisms of action were explored by analyzing a series of pain biomarkers in the ipsilateral dorsal root ganglion (DRG) and the spinal cord. C57Bl6 mice received either SNI- or a sham surgery 14 days before being treated with either rBoNT/A1 or vehicle. Mechanical sensitivity was evaluated in von Frey tests performed at baseline and throughout the experiment. DRGs and spinal cords were collected for quantitative microscopy of immunohistochemically labelled pain-related targets. rBoNT/A1-injection resulted in significant and prolonged (up to 14 days) increases in mechanical threshold compared to vehicle in SNI-operated mice. Volume of type B DRG neurons and number density of Iba1-positive cells in DRG were significantly increased in the SNI-operated animals in comparison to the sham-operated controls, however no significant effect of rBoNT/A1 could be demonstrated. Among spinal cord biomarkers, no effects were observed. These results demonstrate that rBoNT/A1 reduces mechanical allodynia following peripheral nerve injury, but the mechanisms remain elusive. Investigating these biomarkers in a challenged system (diabetes, chemotherapy, etc.) might extend the window of activation, possibly better exposing analgesic mechanisms of rBoNT/A1.