title: Evidence that spinal segmental nitric oxide mediates tachyphylaxis to peripheral local anesthetic nerve block.
abstract: BACKGROUND
  Tachyphylaxis to sciatic nerve blockade in rats correlates with hyperalgesia. Spinal inhibition of nitric oxide synthase with N(G)nitro-L-arginine methyl ester (L-NAME) has been shown to prevent hyperalgesia. Given systemically, L-NAME also prevents tachyphylaxis. The action of L-NAME in preventing tachyphylaxis therefore may be mediated at spinal sites. We compared systemic versus intrathecal potency of L-NAME in modulating tachyphylaxis to sciatic nerve block.
  
  
  METHODS
  Rats were prepared with intrathecal catheters. Three sequential sciatic nerve blocks were placed. Duration of block of thermal nocifensive, proprioceptive and motor responses was recorded. We compared spinal versus systemic dose-response to L-NAME, and examined effects of intrathecal arginine on tachyphylaxis. An additional group of rats underwent testing after T10 spinal cord transection. In these rats duration of sciatic nerve block was assessed by determining the heat-induced flexion withdrawal reflex.
  
  
  RESULTS
  L-NAME was 25-fold more potent in preventing tachyphylaxis given intrathecally than intraperitoneally. Intrathecal arginine augmented tachyphylaxis. Spinalized rats exhibited tachyphylaxis to sciatic block.
  
  
  CONCLUSIONS
  The increased potency of intrathecal versus systemic L-NAME suggests a spinal site of action in inhibiting tachyphylaxis. Descending pathways are not necessary for the development of tachyphylaxis since it occurs even after T10 spinal cord transection. Thus tachyphylaxis, like hyperalgesia, is mediated at least in part by a spinal site of action.
authors.affiliation: Department of Anesthesia, Children's Hospital, Boston, Massachusetts, USA.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.forename: M G
authors.initials: MG
authors.lastname: Sholas
authors.forename: C B
authors.initials: CB
authors.lastname: Berde
authors.forename: J
authors.initials: J
authors.lastname: DiCanzio
authors.forename: D
authors.initials: D
authors.lastname: Zurakowski
authors.forename: R T
authors.initials: RT
authors.lastname: Wilder
mesh_terms: D000779:Anesthetics, Local / Q000009:adverse effects*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009407:Nerve Block / Q000009:adverse effects*; D009569:Nitric Oxide / Q000502:physiology*; D011343:Procaine / Q000009:adverse effects* / Q000031:analogs & derivatives*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000502:physiology*; D013618:Tachyphylaxis
chemical_list: D000779:Anesthetics, Local; D009569:Nitric Oxide; D011343:Procaine; C004616:chloroprocaine; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester