Intradermally injected abobotulinumtoxinA, administered in intact animals preemptively, before surgery, alleviates post-surgical pain, reduces distress and normalizes behavior in a translational animal model

Abstract

Previously, abobotulinumtoxinA (aboBoNT-A) injected intraoperatively using intradermal (ID) route was shown to result in effective, but delayed post-surgical analgesia in pigs. Here, we explore the efficacy of preemptively administered aboBoNT-A in intact animals on pain and associated anxiety/depression-like reactivity following a surgery on the lower back of pigs. AboBoNT-A (200 U/animal) or saline, distributed across ten injection points, were injected around anticipated incision via ID route 15, 5, or 1 day before surgery (part A) or via ID, intramuscular (IM) or subcutaneous (SC) routes 15 days before surgery (part B). Animals were assessed for mechanical sensitivity, distress behaviors, and latency to approach the investigator before and after surgery for 7 days. AboBoNT-A, injected ID 15 days before surgery, didn’t alter any baseline behaviors, but largely prevented the onset of post-surgical allodynia, distress and normalized approaching behavior. Injections made 5 days before surgery led to similar analgesic responses, while those made 1 day before surgery were less effective. IM or SC injections of aboBoNT-A were ineffective. Thus, aboBoNT-A administered ID between 15 and 5 days before surgery represents the most optimal conditions for postoperative analgesia. These findings warrant for clinical investigation of analgesic efficacy of preemptively administered aboBoNT-A in postsurgical pain.