Distinct neurotoxic effects of select local anesthetics on facial nerve injury and recovery

Article type: Research Article

Authors: Byram, Susanna C.^{a; b; c; *} | Bialek, Samantha E.^{b; c} | Husak, Vicki A.^b | Balcarcel, Daniel^{c; 1} | Park, James^{c; 2} | Dang, Jacquelyn^c | Foecking, Eileen M.^{b; d}

Affiliations: [a] Department of Anesthesiology, Loyola University Medical Center, Maywood, IL, Byram – current, USA | [b] Research Service, Department of Veterans Affairs, Edward Hines Jr. VA Hospital, Hines, IL, USA | [c] Stritch School of Medicine, Loyola University Medical Center, Maywood, IL, USA | [d] Department of Otolaryngology—Head and Neck Surgery, Loyola University Medical Center, Maywood, IL, USA

Correspondence: [*] Corresponding author: Susanna C. Byram, MD, PhD, Loyola University Medical Center, 2160 S. First Ave. Maywood, IL, 60153, USA. Tel.: +1 708 216 3754; Fax: +1 708 216 8267; E-mail: Susanna.Byram@lumc.edu.

Note: [1] Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL (Balcarcel - current), USA.

Note: [2] Department of Anesthesia, Brown University/Rhode Island Hospital, Providence, RI, (Park – current), USA.

Abstract: Background:Local anesthetic toxicity has been well-documented to cause neuronal injury, death, and dysfunction, particularly in a susceptible nerve. Objective:To determine whether select local anesthetics affect neuron survival and/or functional recovery of an injured nerve. Methods:This report describes 6 separate experiments that test immediate or delayed application of local anesthetics in 3 nerve injury models. Adult C57/black6 male mice underwent a facial nerve sham, transection, or crush injury. Local anesthetic or saline was applied to the facial nerve at the time of injury (immediate) or 1 day after injury (delayed). Average percent facial motoneuron (FMN) survival was evaluated four-weeks after injury. Facial nerve regeneration was estimated by observing functional recovery of eye blink reflex and vibrissae movement after facial nerve crush injury. Results:FMN survival after: transection + immediate treatment with ropivacaine (54.8%), bupivacaine (63.2%), or tetracaine (66.9%) was lower than saline (85.5%) and liposomal bupivacaine (85.0%); crush + immediate treatment with bupivacaine (92.8%) was lower than saline (100.7%) and liposomal bupivacaine (99.3%); sham + delayed treatment with bupivacaine (89.9%) was lower than saline (96.6%) and lidocaine (99.5%); transection + delayed treatment with bupivacaine (67.3%) was lower than saline (78.4%) and liposomal bupivacaine (77.6%); crush + delayed treatment with bupivacaine (85.3%) was lower than saline (97.9%) and lidocaine (96.0%). The average post-operative time for mice to fully recover after: crush + immediate treatment with bupivacaine (12.83 days) was longer than saline (11.08 days) and lidocaine (10.92 days); crush + delayed treatment with bupivacaine (16.79 days) was longer than saline (12.73 days) and lidocaine (11.14 days). Conclusions:Our data demonstrate that some local anesthetics, but not all, exacerbate motoneuron death and delay functional recovery after a peripheral nerve injury. These and future results may lead to clinical strategies that decrease the risk of neural deficit following peripheral nerve blocks with local anesthetics.

Keywords: Neurotoxicity, motoneuron survival, peripheral nerve block, local anesthetic toxicity, peripheral nerve injury, facial nerve injury, liposomal bupivacaine, regional anesthesia

DOI: 10.3233/RNN-190987

Journal: Restorative Neurology and Neuroscience, vol. 38, no. 2, pp. 173-183, 2020