NMDA and purinergic processes modulate neck muscle activity evoked by noxious stimulation of dura

Background: Adenosine triphosphate (ATP) and glutamate are associated with some headache conditions, and purinergic (P2X) and glutamatergic N-methyl-D-aspartate (NMDA) receptor-related processes in the medulla can modulate the effects of trigeminal nociceptive afferent inputs into the brainstem on craniofacial sensorimotor circuits. This study aimed to test whether neck muscle activity can be induced in rats by noxious stimulation of the frontal dura or superior sagittal sinus that involves P2X or NMDA receptor-dependent mechanisms.

Methods: While electromyographic activities of neck and craniofacial muscles were being recorded in anesthetized rats (n = 46), the inflammatory irritant mustard oil (0.2 µL, 20% MO) or vehicle (mineral oil) was topically applied to the dura or sinus, preceded by 10 µL of the ATP antagonist 2',3'-O-(2,4,6- trinitrophenyl) adenosine 5'-triphosphate (TNP-ATP, 0.1 mmol/L; n = 8) or 2-amino-5-phosphonopentanoic acid (APV, 0.05 mmol/L; n = 7) or phosphate-buffered saline (PBS as vehicle control; n = 10).

Results: Application of MO but not vehicle to the frontal dura significantly increased (P < .05) neck electromyographic activity whereas MO application to the superior sagittal sinus did not significantly increase neck electromyographic activity unless MO had previously been applied to the dura. Pre-treatment (i.t.) with TNP-ATP or APV but not vehicle control significantly reduced neck electromyographic activity evoked by MO application to the dura.

Conclusions: These data suggest that noxious stimulation of the frontal dura (but not superior sagittal sinus) may enhance neck muscle activity that is P2X and NMDA receptor-dependent. These effects may contribute to neck muscle stiffness that occurs in some headache conditions.

Keywords: animal pain model; craniofacial pain; dura; glutamatergic; headache; mustard oil; purinergic.