The anti-migraine agent sumatriptan constricts cerebral blood vessels, and also blocks neuropeptide release from meningeal sensory neurons. We investigated whether sumatriptan can also affect neuronal discharge, by recording the activity of dural primary afferent neurons during dural application of sumatriptan in anesthetized rats. Sumatriptan (0.24-24 microM) induced a concentration-dependent increase in ongoing discharge. The discharge occurred only in the presence of calcium. The suppressive effect of calcium removal was not a result of a general decrease in excitability, because calcium removal produced a pronounced increase in mechanically evoked discharge. The excitatory effect on dural afferent discharge might underlie the initial worsening of the headache that can occur following sumatriptan administration, prior to the subsequent onset of headache relief.