Botulinum Toxin B Affects Neuropathic Pain but Not Functional Recovery after Peripheral Nerve Injury in a Mouse Model

Toxins (Basel). 2018 Mar 18;10(3):128. doi: 10.3390/toxins10030128.

Abstract

Clinical use of neurotoxins from Clostridium botulinum is well established and is continuously expanding, including in treatment of pain conditions. Background: The serotype A (BoNT/A) has been widely investigated, and current data demonstrate that it induces analgesia and modulates nociceptive processing initiated by inflammation or nerve injury. Given that data concerning the serotype B (BoNT/B) are limited, the aim of the present study was to verify if also BoNT/B is able not only to counteract neuropathic pain, but also to interfere with inflammatory and regenerative processes associated with the nerve injury. Methods: As model of neuropathic pain, chronic constriction injury (CCI) of the sciatic nerve was performed in CD1 male mice. Mice were intraplantarly injected with saline (control) or BoNT/B (5 or 7.5 pg/mouse) into the injured hindpaw. For comparison, another mouse group was injected with BoNT/A (15 pg/mouse). Mechanical allodynia and functional recovery of the injured paw was followed for 101 days. Spinal cords and sciatic nerves were collected at day 7 for immunohistochemistry. Results and Conclusions: The results of this study show that BoNT/B is a powerful biological molecule that, similarly to BoNT/A, can reduce neuropathic pain over a long period of time. However, the analgesic effects are not associated with an improvement in functional recovery, clearly highlighting an important difference between the two serotypes for the treatment of this chronic pain state.

Keywords: Schwann cells; allodynia; glia; immunohistochemistry; nerve regeneration; sciatic static index; spinal cord; walking track analysis; weight bearing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / therapeutic use*
  • Animals
  • Biomarkers / metabolism
  • Botulinum Toxins, Type A / therapeutic use*
  • Disease Models, Animal
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / metabolism
  • Male
  • Mice
  • Neuralgia / drug therapy*
  • Neuralgia / metabolism
  • Peripheral Nerve Injuries / drug therapy*
  • Peripheral Nerve Injuries / metabolism
  • Sciatic Nerve / injuries
  • Sciatic Nerve / metabolism
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism

Substances

  • Analgesics
  • Biomarkers
  • rimabotulinumtoxinB
  • Botulinum Toxins, Type A