Inhibition of nitric oxide synthases prevents and reverses alpha,beta-meATP-induced neck muscle nociception in mice.
BACKGROUND
Tension-type headache (TTH) is associated with noxious input from neck muscles. Intravenous administration of the unspecific nitric oxide synthase inhibitor L-NMMA in chronic TTH patients caused analgesia and reduction of neck muscle tenderness.


METHODS
The unspecific nitric oxide synthase inhibitor L-NMMA was applied in an experimental model for neck muscle nociception in anesthetized mice (N = 25).


RESULTS
Local injection of α,β-meATP into semispinal neck muscles induced sustained facilitation of brainstem nociception as monitored by the jaw-opening reflex. Preceding intraperitoneal administration of L-NMMA (0.05, 0.1, 1 mg/kg) prevented reflex facilitation evoked by α,β-meATP in a dose-dependent manner. Intraperitoneal injection of L-NMMA subsequent to intramuscular α,β-meATP application reversed established brainstem reflex facilitation back to baseline values.


CONCLUSIONS
Both experiments with preceding and subsequent L-NMMA indicate the involvement of nitric oxide synthases in the induction and maintenance of facilitation. However, future experiments will have to address the involvement of various isoenzymes in order to provide for new therapeutic concepts in TTH.
Ellrich
Jens
J
Medical Physiology & Experimental Pharmacology Group, Centre for Sensory-Motor Interaction, Department of Health Science and Technology, Medical Faculty, Aalborg University, Denmark. jellrich@hst.aau.dk
Fischer
Andreas
A
Gilsbach
Joachim M
JM
Makowska
Anna
A
Spangenberg
Peter
P
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009334:Neck Muscles / Q000187:drug effects*; D019547:Neck Pain / Q000139:chemically induced / Q000517:prevention & control*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; C002630:alpha,beta-methyleneadenosine 5'-triphosphate