Glutamatergic transmission in the trigeminal nucleus assessed with local blood flow

Stimulation of the superior sagittal sinus in humans is pain-producing and in experimental animals leads to excitation of neurons in the caudal trigeminal nucleus and dorsal horns of the C(1/)C(2) cervical spinal cord: the trigeminocervical complex. Neuronal excitation is generally associated with an increase in local blood flow due to flow/metabolism coupling and we have used local blood flow in the trigeminocervical complex to examine the role of N-methyl-D-aspartate (NMDA)-mediated transmission in these neurons. Cats were anaesthetised with alpha-chloralose (60 mg/kg, ip; supplements 20 mg/kg iv) after surgical preparation under halothane (0.5-3%). Animals were paralysed with gallamine triethiodide to prevent possible movement artefact distorting the laser Doppler signals. The superior sagittal sinus was isolated for electrical stimulation (150 V; 250 microsec duration; 0.5, 1, 2, 5, 10 and 20 Hz) and the dorsal surface of the spinal cord exposed at the C(2) level. Blood flow was recorded from the region over the trigeminocervical complex by careful placement of a laser Doppler flow probe. Flow was recorded continuously by an online collection programme and NMDA-mediated transmission modulated by intravenous administration of MK-801 (0.4, 1 and 4 mg/kg, iv) at the stimulation frequency of 5 Hz. Stimulation of the superior sagittal sinus produced a stimulus-locked, frequency-dependent increase in blood flow in the region of the trigeminocervical complex. The mean maximum response was 39+/-4% at 20 Hz. MK-801 had no effect on the resting flow signal but markedly attenuated the SSS-evoked response in a dose-dependent manner. The mean maximum response after 4 mg/kg MK-801 was 13+/-2%. NMDA-mediated transmission is likely to be involved in nociceptive trigeminovascular transmission within the trigeminocervical complex and offers a possible target for both acute and preventative treatment of migraine.