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

Previously, abobotulinumtoxinA (aboBoNT-A) injected intraoperatively resulted 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 behaviors following a full-skin-muscle incision and retraction surgery on the lower back. AboBoNT-A (200 U/animal) or saline, distributed across ten points, were injected around anticipated incision 15, 5, or 1 day before surgery via ID route (part A) or 15 days before surgery via ID, intramuscular (IM) or subcutaneous (SC) routes (part B). We assessed mechanical sensitivity (withdrawal force; WF), distress behavior score (DBS), 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 resulted in 5-fold increases in WF, 75% reduction in DBS and 70% reduction in approach latencies (all p < 0.01). Injections 5 days before surgery led to similar effects, albeit with a fewer animals reaching thresholds, while those made 1 day before surgery were less effective. SC and IM injections were ineffective. Thus, aboBoNT-A administered ID 15 days before surgery represents the most optimal condition for postoperative analgesia. These findings warrant for clinical investigation of preemptively administered aboBoNT-A in postsurgical pain.