EFFECTS OF BOTULINUM NEUROTOXIN TYPE B IN NEUROPATHIC MICE: BEHAVIORAL AND IMMUNOHISTOCHEMICAL INVESTIGATIONS

Background and aims. Therapeutic use of botulinum neurotoxins is well established and is continuously expanding in clinical practice, including pain conditions. In animal models, 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. The aim of the present study was to verify if also the serotype B (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. Chronic Constriction Injury (CCI) of the sciatic nerve was performed in CD1 male mice. Mice were intraplantarly injected with BoNT/B (5 or 7.5 pg/mouse) into the injured hind paw. 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. The results of this study show that BoNT/B is a powerful biological molecule that can reduce neuropathic pain over a long period of time. However, we provide the first evidence that BoNT/B increases the expression of cells that release pro-inflammatory molecules in injured nerve and, in ventral horns of spinal cord, induces reactive astrogliosis development that could lead to glial scar formation. Conclusions. On the basis of our study we do not recommend the use of BoNT/Bin pain conditions associated with nerve injury as long as the molecular pharmacology and the mechanism of action of neurotoxin will not fully understood.