Native botulinum toxin type A vs. redesigned botulinum toxins in pain: What did we learn so far?

Driven by the clinical success of botulinum toxin serotype A (BoNT/A) and the need for improved chronic pain management, researchers attempted to develop re-designed botulinum toxin (BoNT)-based molecules as novel analgesics. Various recombinant protein expression strategies including retargeted binding domains, and chimeric toxins combining different serotypes were tested to improve BoNT/A therapeutic safety margin and expand its efficacy. The aim of this review is to re-evaluate the current design strategies for recombinant BoNT-based molecules for pain treatment, compares their analgesic profile against the native BoNT/A, as well as to discuss the main strengths and potential weaknesses of reported approaches.