title: Comparison of histopathological effects of perineural administration of bupivacaine and bupivacaine-dexmedetomidine in rat sciatic nerve.
abstract: Injection of a variety of drugs such as local anesthetics (LAs) for peripheral nerve block has been shown to cause damage to peripheral nerves. Bupivacaine is a local anesthetic widely used in surgical procedures. The aim of this study was to evaluate the neurotoxicity of LAs including Bupivacaine and dexmedetomidine (DEX)-Bupivacaine on sciatic nerve tissue at histopathological level. In addition, we investigated whether perineural administration of DEX can attenuate Bupivacaine-induced neurotoxicity. Twenty adult Sprague Dawley rats received unilateral sciatic nerve blocks with either 0.2ml of 0.5% bupivacaine (n=8) or 0.5% bupivacaine plus 0.005% DEX (n=8) or normal saline (0.9%, as control group) (n=4) in the left hind extremity. Sciatic nerves were harvested at 14days post-injection and analyzed for nerve damage using ultrastructure and histopathologic analysis. Histopathology of sciatic nerve at day 14 post-injection showed a variable degree of neuronal injury associated with perineural inflammation in each treatment group and was classified as none or mild, intermediate or severe. Administration of both LAs resulted in a significant decrease in the total number of myelinated fibers per nerve (95% CI for group difference: Bupivacaine, P=0.001, DEX-Bupivacaine, P=0.036) compared to the saline control group. Animals that received these perineural local anesthetics (LAs) injections showed increased severity of injury compared to the control group. Animals in the DEX-Bupivacaine group had higher perineural inflammation and nerve damage than those of the saline control group and less than those of the Bupivacaine group at day 14 post-injection. Quantitatively, average total nerve fiber per nerve and average myelinated nerve fiber density in the injured region of the Bupivacaine-treated group was less than that of the DEX-Bupivacaine-treated group. LAs injection into the nerve causes peripheral nerve damage and remains an important clinical danger. Bupivacaine is associated with considerable histopathological changes, including edema of the perineurium and myelin degeneration with Wallerian degeneration, when injected perineurally. Perineural DEX added to a clinical concentration of bupivacaine attenuates the Bupivacaine-induced injuries.
authors.affiliation: Anesthesiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Memari
authors.affiliation: Department of General Surgery, Shahid Beheshti University of Medical Science, College of Medicine, Emam Hosein Hospital, Tehran, Iran.
authors.forename: Mohammad-Ali
authors.initials: MA
authors.lastname: Hosseinian
authors.affiliation: Anesthesiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Mirkheshti
authors.affiliation: Department of Emergency Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Arhami-Dolatabadi
authors.affiliation: Anesthesiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Mirabotalebi
authors.affiliation: Anesthesiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Khandaghy
authors.affiliation: Shiraz Molecular Pathology Research Center, Dr. Daneshbod Pathology Laboratory, Shiraz, Iran.
authors.forename: Yahya
authors.initials: Y
authors.lastname: Daneshbod
authors.affiliation: Shefa Neuroscience Research Center, Khatam-Al-Anbia Hospital, Tehran, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Alizadeh
authors.affiliation: Department of Pathology, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran; Shefa Neuroscience Research Center, Khatam-Al-Anbia Hospital, Tehran, Iran; Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: s-shirian@razi.tums.ac.ir.
authors.forename: Sadegh
authors.initials: S
authors.lastname: Shirian
mesh_terms: D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000633:toxicity*; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D046529:Microscopy, Electron, Transmission; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure
chemical_list: D000779:Anesthetics, Local; D020927:Dexmedetomidine; D002045:Bupivacaine
keywords: Bupivacaine; Dexmedetomidine; Electron microscopy; Histopathology; Nerve damage