title: Neuronal nitric oxide synthase is involved in the induction of nerve growth factor-induced neck muscle nociception.
abstract: BACKGROUND
  Neck muscle nociception mediated by nitric oxide may play a role in the pathophysiology of tension-type headache.
  
  
  OBJECTIVE
  The present study addresses the involvement of neuronal nitric oxide synthase (nNOS) in the facilitation of neck muscle nociception after local application of nerve growth factor (NGF).
  
  
  METHODS
  After administration of NGF into semispinal neck muscles, the impact of neck muscle noxious input on brainstem processing was monitored by the jaw-opening reflex in anesthetized mice. The modulatory effect of preceding and subsequent administration of an inhibitor of neuronal nitric oxide synthase on central facilitation was addressed in a controlled study.
  
  
  RESULTS
  With preceding i.p. application of saline or 0.096 mg/kg of the specific nNOS inhibitor Nω-propyl-L-arginine (NPLA), NGF induced a sustained reflex facilitation within 60 minutes. Preceding injection of 0.96 mg/kg or 1.92 mg/kg NPLA completely prevented the potentially facilitatory effect of NGF. Subsequent administration of 0.96 mg/kg NPLA did not affect established NGF-evoked reflex facilitation. Thus, NPLA prevents facilitation of brainstem processing by noxious myofascial input from neck muscles in a dose-dependent manner.
  
  
  CONCLUSIONS
  These findings suggest that nNOS is involved in the induction but not the maintenance of NGF-evoked facilitation of nociception in the brainstem. These results from an experimental animal model may support the idea of NOS and nNOS as potential targets for pharmacological treatment of tension-type headache.
authors: Experimental Neurosurgery Section, Department of Neurosurgery, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors: Andreas
authors: A
authors: Isaak
authors: Jens
authors: J
authors: Ellrich
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001933:Brain Stem / Q000201:enzymology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009334:Neck Muscles / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology; D020932:Nerve Growth Factor / Q000633:toxicity; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D010146:Pain / Q000201:enzymology* / Q000503:physiopathology; D012018:Reflex / Q000187:drug effects; D018781:Tension-Type Headache / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology
chemical_list: D004791:Enzyme Inhibitors; C109599:N(omega)-propylarginine; D020932:Nerve Growth Factor; D001120:Arginine; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse