Studies on myofascial pain usually apply a,b-meATP due to its narrow receptor profile (P2X3) and sustained stability. In contrast, native ATP is quickly degraded to metabolites and interacts with excitatory P2X and inhibitory P2Y receptors. The present study addressed divergent effects of a,b-meATP and ATP administration (1 mmol/l, 20 ml) in semispinal neck muscle in mice under general anesthesia (n=20). The impact of noxious neck muscle input on brainstem nociception was monitored by the jaw-opening reflex (JOR) elicited by electrical tongue stimulation. Bilateral intramuscular (i.m.) injection of a,b-meATP facilitated the JOR by 203% within two hours, whereas an effect was missing with ATP. Considering interactions of ATP with P2Y1 receptors, the antagonist MRS2179 (1mmol/l i.m.) was applied before i.m. ATP (n=10). With preceding MRS2179, ATP induced reflex facilitation of 117%. Vice versa, i.m. administration of the P2Y1 agonist MeS-ADP during established JOR facilitation two hours after i.m. a,b-meATP induced complete recovery of the reflex down to baseline (n=10). The results demonstrate opposing excitatory P2X3 and inhibitory P2Y1 effects of ATP in neck muscle nociceptive processing in mice. These mechanisms may be involved in the pathophysiology of neck muscle pain in man.