The trigeminally mediated jaw-depressor reflex (JDR) may be a suitable model system in which to study central actions of anti-migraine agents (Jenkins et al. 2000). The present study was designed to investigate interactions between dural afferents and the JDR, which involve different divisions of the trigeminal nerve, by studying effects upon the reflex of intracisternal administration of capsaicin (Cutrer et al. 1995). For comparison, a hindlimb flexion withdrawal reflex (FWR) has also been recorded.

Experiments were performed in twelve rabbits anaesthetized with pentobarbitone sodium (initial dose 44 mg kg^-1, maintenance infusion 14 mg kg^-1 h^-1). The JDR was evoked by electrical stimulation of the tongue and recorded from the left digastric muscle, while the FWR was elicited by electrical stimulation of the toes and recorded from the left tibialis anterior (TA) muscle. Reflexes were evoked by 1 ms stimuli delivered in blocks of 8 at 1 Hz, and were quantified from averaged, full-wave rectified EMG signals. Capsaicin was dissolved in 15 ml DMSO and delivered to the cisterna magna in doses of 15 (n = 6) or 150 mg (n = 6). Five animals received DMSO alone prior to administration of capsaicin. Experiments were terminated by overdose of pentobarbitone followed by I.V. injection of saturated KCl solution.

Intracisternal DMSO had no significant effect on either the JDR or FWR (Friedman’s ANOVA, P > 0.3). Given at 15 mg, capsaicin significantly (Friedman’s, P < 0.0001) inhibited both the JDR and the FWR to medians of 10 (interquartile range (IQR) 6-26 %) and 17 % (IQR 11-27 %) of pre-drug controls, respectively. In both cases only the first time point post-capsaicin (1-3 min) was significantly different from control (Dunnett’s post test, P < 0.05). Capsaicin (150 mg) also significantly (Friedman’s, P < 0.0001) inhibited both reflexes (median maximum inhibition 7 and 46 % of pre-drug controls for JDR and FWR, respectively), but in this case responses were significantly different from controls for 13Ð15 min after the stimulus (Dunnett’s, P < 0.05).

Thus intracisternal capsaicin inhibited both the JDR and FWR, with the higher dose inducing a longer-lasting effect. Suppression of the spinally mediated FWR indicates that the inhibition is not due to non-specific dysfunction of brainstem transmission. Our interpretation of these results is that stimulation of dural afferents (presumably C-fibres) by capsaicin activates diffuse noxious inhibitory control systems (Falinower et al. 1994) that impinge on neurones contributing to the JDR and FWR.

S.J. is supported by Merck, Sharp and Dohme.

All procedures accord with UK legislation.