Noxious input from the neck muscle plays a pivotal role in pathophysiology of tension-type headache. In present study noxious stimulation of semispinal neck muscles was performed by bilateral injection of ATP (100 nmol/l, 20 ml) or nerve growth factor (NGF, 0.8 mmol/l, 20 ml) in anesthetized mice (n=49). The impact of neck muscle noxious input on craniofacial nociceptive processing was tested using the jaw-opening reflex (JOR) elicited by electrical tongue stimulation. Single injection of ATP or NGF induced sustained facilitation of the JOR. In order to investigate the role of group III or IV muscle afferents in ATP and NGF-induced JOR facilitation, tetrodotoxin (TTX, 30 to 100 nmol/l; 20 ml) was intramuscularly applied 15 min before or 30 min after ATP or NGF injection. Preceding and subsequent injection of TTX reduced the ATP-induced effect in a dose-dependent manner. However, NGF-evoked effect was not affected by administration of TTX. Induction and maintenance of long-term facilitation by ATP is mediated by TTX-sensitive group III muscle afferents. Long-term effects after NGF administration may be due to excitation of group IV muscle afferents. Supported by grants of the German Headache Consortium (BMBF, 01EM05160).