The Activities of Recombinant Botulinum Toxin A on Spared Nerve Injury-Induced Neuropathic Pain in a Diabetic Mice Model

Diabetic neuropathy is characterized by nerve damage and chronic neuropathic pain and lacks effective treatment. Botulinum neurotoxin type A (BoNT/A), a neurotoxin with established therapeutic use in neurological disorders, has emerged as a potential analgesic agent. This study investigated the effects of a recombinant form of BoNT/A1 (rBoNT/A1) on neuropathic pain induced by spared nerve injury (SNI) in a diabetic mouse model. Thirty-two adult male C57BL/6JRj diabetic mice were subjected to SNI or sham surgery. Fourteen days post surgery, mice received an intraplantar dose of rBoNT/A1 or vehicle. Mechanical allodynia was assessed using von Frey filaments, and spinal cord and sciatic nerve tissues were analyzed via immunohistochemistry and transmission electron microscopy to evaluate glial activation, neurotransmitter receptor expression, and axonal morphology. The results demonstrated that rBoNT/A1 significantly alleviated mechanical allodynia and caused a marked reduction in Iba1-positive microglial activation in the spinal cord, whereas no significant changes were observed in astrocyte (GFAP) density or GABAAR subunit expression. Additionally, rBoNT/A1 treatment did not significantly alter axon diameter, myelin thickness, or C-fiber morphology. In conclusion, intraplantar administration of rBoNT/A1 reduced SNI-induced mechanical allodynia in diabetic mice, potentially by attenuating spinal microglial activation, supporting the therapeutic promise of rBoNT/A1 in managing diabetic neuropathic pain.