title: Perineural administration of dexmedetomidine in combination with bupivacaine enhances sensory and motor blockade in sciatic nerve block without inducing neurotoxicity in rat.
abstract: BACKGROUND
  The current study was designed to test the hypothesis that high-dose dexmedetomidine added to local anesthetic would increase the duration of sensory and motor blockade in a rat model of sciatic nerve blockade without causing nerve damage.
  
  
  METHODS
  Thirty-one adult Sprague-Dawley rats received bilateral sciatic nerve blocks with either 0.2 ml bupivacaine, 0.5%, and 0.5% bupivacaine plus 0.005% dexmedetomidine in the contralateral extremity, or 0.2 ml dexmedetomidine, 0.005%, and normal saline in the contralateral extremity. Sensory and motor function were assessed by a blinded investigator every 30 min until the return of normal sensory and motor function. Sciatic nerves were harvested at either 24 h or 14 days after injection and analyzed for perineural inflammation and nerve damage.
  
  
  RESULTS
  High-dose dexmedetomidine added to bupivacaine significantly enhanced the duration of sensory and motor blockade. Dexmedetomidine alone did not cause significant motor or sensory block. All of the nerves analyzed had normal axons and myelin at 24 h and 14 days. Bupivacaine plus dexmedetomidine showed less perineural inflammation at 24 h than the bupivacaine group when compared with the saline control.
  
  
  CONCLUSIONS
  The finding that high-dose dexmedetomidine can safely improve the duration of bupivacaine-induced antinociception after sciatic nerve blockade in rats is an essential first step encouraging future studies in humans. The dose of dexmedetomidine used in this study may exceed the sedative safety threshold in humans and could cause prolonged motor blockade; therefore, future work with clinically relevant doses is necessary.
authors: Department of Anesthesiology, Division of Pain Medicine, The University of Michigan Health System, 7433 Medical Sciences Building 1, 1150 West Medical Center Drive, Ann Arbor, Michigan 48109-5615, USA. cbrummet@umich.edu
authors: Chad M
authors: CM
authors: Brummett
authors: Mary A
authors: MA
authors: Norat
authors: John M
authors: JM
authors: Palmisano
authors: Ralph
authors: R
authors: Lydic
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D007249:Inflammation / Q000139:chemically induced; D008297:Male; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects*; D009407:Nerve Block / Q000379:methods*; D020258:Neurotoxicity Syndromes / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects* / Q000502:physiology; D012677:Sensation / Q000187:drug effects*; D012965:Sodium Chloride / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D018712:Analgesics, Non-Narcotic; D000779:Anesthetics, Local; D012965:Sodium Chloride; D020927:Dexmedetomidine; D002045:Bupivacaine