title: Spinal procaine is less neurotoxic than mepivacaine, prilocaine and bupivacaine in rats.
abstract: OBJECTIVE
  Lidocaine has been reported to be more neurotoxic than other local anesthetics. Alternatives to lidocaine with lower toxicity and shorter duration of action are desirable. Therefore, we compared the histologic and functional changes induced by intrathecal injection of prilocaine, mepivacaine, procaine, and bupivacaine in rats.
  
  
  METHODS
  Rats (n = 184) randomly received via an intrathecal catheter 0.12 microL/g body weight of 2%, 10%, 16%, or 20% prilocaine, mepivacaine, or procaine; 0%, 0.5%, 2.5%, 4%, or 5% bupivacaine in distilled water; or distilled water or 15% glucose solution alone as a control. We evaluated neurofunction by analyzing walking behavior and sensory threshold and examined the L3 spinal cord, posterior and anterior roots, and cauda equina by light and electron microscopy.
  
  
  RESULTS
  The recovery time to normal ambulation after intrathecal injection was significantly faster with procaine than with the other 3 drugs at all concentrations. There were no significant differences in the sensory threshold among the 4 anesthetics. Histologic damage was observed only in rats treated with greater than 16% prilocaine or mepivacaine or with greater than 4% bupivacaine. Histologic damage occurred at the posterior root and posterior white matter and was characterized by axonal degeneration. Rats treated with procaine, even at 20%, showed no histologic abnormalities.
  
  
  CONCLUSIONS
  In this animal model, the neurotoxicity of intrathecal procaine was the mildest, and the recovery time to ambulation with procaine was the fastest among the 4 tested anesthetics.
authors: Department of Anesthesiology, Kitasato University School of Medicine, Japan. takenami@med.kitasato-u.ac.jp
authors: Tamie
authors: T
authors: Takenami
authors: Saburo
authors: S
authors: Yagishita
authors: Yoshihiro
authors: Y
authors: Nara
authors: Yang-Hsi
authors: YH
authors: Tsai
authors: Hiromi
authors: H
authors: Hiruma
authors: Tadashi
authors: T
authors: Kawakami
authors: Sumio
authors: S
authors: Hoka
mesh_terms: D000779:Anesthetics, Local / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000648:ultrastructure; D001522:Behavior, Animal / Q000187:drug effects; D002045:Bupivacaine / Q000008:administration & dosage / Q000633:toxicity*; D007278:Injections, Spinal; D008161:Lumbosacral Region; D008297:Male; D008619:Mepivacaine / Q000008:administration & dosage / Q000633:toxicity*; D023421:Models, Animal; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects; D011318:Prilocaine / Q000008:administration & dosage / Q000633:toxicity*; D011343:Procaine / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000648:ultrastructure; D013997:Time Factors; D016138:Walking
chemical_list: D000779:Anesthetics, Local; D011318:Prilocaine; D011343:Procaine; D008619:Mepivacaine; D002045:Bupivacaine