title: NG-nitro-L-arginine methyl ester (L-NAME) prevents tachyphylaxis to local anesthetics in a dose-dependent manner.
abstract: A model of local anesthetic tachyphylaxis was developed in our group previously using repeated sciatic nerve blocks in rats. In this model, thermal hyperalgesia accelerated tachyphylaxis, and the noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, MK-801, prevented both hyperalgesia and tachyphylaxis. Nitric oxide is thought to be a second messenger for NMDA pathways in the spinal cord, and appears to be involved in spinal mechanisms of hyperalgesia. We hypothesized that nitric oxide synthase inhibitors would also inhibit the development of tachyphylaxis. Repeated rat sciatic nerve blocks were placed by percutaneous injection of 2-chloroprocaine. Block duration was tested by measuring hot-plate latency at 56 degrees C. Two hours before the first nerve block, rats received intraperitoneal injections with saline or one of six concentrations of NG-nitro-L-arginine methyl ester (L-NAME) in a randomized, blinded pattern. Control rats developed tachyphylaxis as seen previously: the duration of the third block was 30% that of the first. L-NAME inhibited the development of tachyphylaxis in a dose-dependent manner; tachyphylaxis was inhibited by 50% using L-NAME at 0.2mg/kg and completely abolished by 50 mg/kg. Nitric oxide pathways may be involved in the development of tachyphylaxis to local anesthetic nerve block.
authors.affiliation: Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Wilder
authors.forename: M G
authors.initials: MG
authors.lastname: Sholas
authors.forename: C B
authors.initials: CB
authors.lastname: Berde
mesh_terms: D000779:Anesthetics, Local / Q000009:adverse effects*; D000818:Animals; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D006358:Hot Temperature; D006930:Hyperalgesia / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000627:therapeutic use*; D009407:Nerve Block; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011343:Procaine / Q000009:adverse effects / Q000031:analogs & derivatives*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012584:Sciatic Nerve / Q000187:drug effects; D015290:Second Messenger Systems / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects; D013618:Tachyphylaxis / Q000502:physiology*
chemical_list: D000779:Anesthetics, Local; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D011343:Procaine; C004616:chloroprocaine; D016291:Dizocilpine Maleate; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester