Intraoperative abobotulinumtoxinA alleviates pain after surgery and improves general wellness in a translational animal model

• Published in: Scientific reports Vol. 12; no. 1; p. 21555
• Main Authors: Cornet, Sylvie, Carré, Denis, Limana, Lorenzo, Castel, David, Meilin, Sigal, Horne, Ron, Pons, Laurent, Evans, Steven, Lezmi, Stephane, Kalinichev, Mikhail
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.12.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 692/308/1426; 692/308/2778; Analgesics; Analgesics - metabolism; Animal models; Animals; Astrocytes; Bupivacaine; Bupivacaine - pharmacology; Calcitonin; Calcitonin gene-related peptide; Calcitonin Gene-Related Peptide - metabolism; Disease Models, Animal; Dorsal horn; Dorsal root ganglia; Ganglia, Spinal - metabolism; Glial fibrillary acidic protein; Humanities and Social Sciences; Hyperalgesia - drug therapy; Hyperalgesia - metabolism; Latency; Mechanical properties; Microglia; multidisciplinary; Pain; Pain perception; Pain, Postoperative - drug therapy; Pain, Postoperative - metabolism; Proteins; Rats; Rats, Sprague-Dawley; Science; Science (multidisciplinary); Skin; SNAP-25 protein; Spinal cord; Spinal Cord - metabolism; Spinal Cord Dorsal Horn - metabolism; Substance P; Surgery; Swine; Wound healing
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-25002-x

Pain after surgery remains a significant healthcare challenge. Here, abobotulinumtoxinA (aboBoNT-A, DYSPORT) was assessed in a post-surgical pain model in pigs. Full-skin-muscle incision and retraction surgery on the lower back was followed by intradermal injections of either aboBoNT-A (100, 200, or 400 U/pig), vehicle (saline), or wound infiltration of extended-release bupivacaine. We assessed mechanical sensitivity, distress behaviors, latency to approach the investigator, and wound inflammation/healing for 5–6 days post-surgery. We followed with immunohistochemical analyses of total and cleaved synaptosomal-associated protein 25 kD (SNAP25), glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor protein-1(Iba1), calcitonin gene-related peptide (CGRP) and substance P (SP) in the skin, dorsal root ganglia (DRG) and the spinal cord of 400 U aboBoNT-A- and saline-treated animals. At Day 1, partial reversal of mechanical allodynia in aboBoNT-A groups was followed by a full reversal from Day 3. Reduced distress and normalized approaching responses were observed with aboBoNT-A from 6 h post-surgery. Bupivacaine reversed mechanical allodynia for 24 h after surgery but did not affect distress or approaching responses. In aboBoNT-A-treated animals cleaved SNAP25 was absent in the skin and DRG, but present in the ipsilateral dorsal horn of the spinal cord. In aboBoNT-A- versus saline-treated animals there were significant reductions in GFAP and Iba1 in the spinal cord, but no changes in CGRP and SP. Analgesic efficacy of aboBoNT-A appears to be mediated by its activity on spinal neurons, microglia and astrocytes. Clinical investigation to support the use of aboBoNT-A as an analgesic drug for post-surgical pain, is warranted.