title: Ropivacaine-induced peripheral nerve injection injury in the rodent model.
abstract: BACKGROUND
  Intraneural administration of local anesthetics has been associated with nerve damage. We undertook the present study to investigate histological changes induced by ropivacaine injection into rat sciatic nerve.
  
  
  METHODS
  Fifty-four adult male Lewis rats were randomly distributed into 9 groups, 6 animals per group. Fifty microliters of normal saline, 10% phenol, or 0.75% ropivacaine were administered by intrafascicular injection, extrafascicular injection, or extraneural (topical) placement. At 2 weeks, animals were killed and the sciatic nerve at the injection site was evaluated with light microscopy, quantitative histomorphometry, and electron microscopy.
  
  
  RESULTS
  On cross-sectional evaluation, extrafascicular ropivacaine injection and extraneural placement of ropivacaine were both associated with damage to the perineurium, with focal demyelination surrounded by edematous endoneurium. Intrafascicular injection of ropivacaine resulted in a wedge-shaped region of demyelination and focal axonal loss with some regeneration, bordered by a region of normally myelinated axons in a background of edematous endoneurium. Extrafascicular injection resulted in more significant damage than extraneural placement of ropivacaine, but less than intrafascicular injection as shown with quantitative histomorphometry. Quantitatively, ropivacaine-injured specimens had significantly lower nerve density than saline-injured specimens. Wallerian degeneration and perineural edema were also demonstrated qualitatively with electron microscopy.
  
  
  CONCLUSIONS
  This study demonstrates that, in the rat model, ropivacaine is associated with marked histological abnormality, including edema of the perineurium and axonal destruction with wallerian degeneration, when injected into or extraneurally placed onto a nerve. Extrafascicular injection and extraneural placement were associated with similar, although milder, histological damage than intrafascicular injection. Further work is needed to investigate the functional implications, if any, of the histological abnormalities observed in this study.
authors.affiliation: Department of Surgery, Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Whitlock
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Brenner
authors.forename: Ida K
authors.initials: IK
authors.lastname: Fox
authors.forename: Arash
authors.initials: A
authors.lastname: Moradzadeh
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hunter
authors.forename: Susan E
authors.initials: SE
authors.lastname: Mackinnon
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000633:toxicity*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001369:Axons / Q000473:pathology; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology; D007150:Immunohistochemistry; D007267:Injections; D008297:Male; D008854:Microscopy, Electron; D009416:Nerve Regeneration; D010525:Peripheral Nerves / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D000077212:Ropivacaine; D012584:Sciatic Nerve / Q000473:pathology; D014855:Wallerian Degeneration / Q000139:chemically induced / Q000473:pathology
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine