The TRPV1 receptor antagonist, A-993610, shows no effect on neurogenic dural dilation but is able to block capsaicin induced dilation (original) (raw)

Cephalalgia

Abstract

Objectives To study the effects of the potent and selective brain penetrant TRPV1 receptor antagonist A-993610 on dural nociceptive and facial mechanical input to the trigeminocervical complex (TCC). Introduction It has been proposed that TRPV1 receptors may play a role in modulating in trigeminal sensory processing. We used a model of trigeminovascular nociceptive activation to test this in the rat. Methods Male Sprague Dawley rats (N = 9) were anesthetized with pentobarbitone (60 mg/kg) and cannulated for monitoring and drug administration. The anesthesia was then maintained by propofol (20–25 mg/kg/h). After appropriate surgical preparation wide-dynamic-range neurons, identified by noxious pinch, and innocuous brush, responding to electrical stimulation of the middle meningeal artery/dura mater (MMA; stimulation parameters: 0.5 Hz, 0.3–0.4 ms,12.6–18 V), were identified and recorded using electrophysiological techniques. A-993610, dissolved in polyethylene glycol 300 (8 mg/ ml), ...

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