The anti-migraine agent sumatriptan induces a calcium-dependent discharge in meningeal sensory neurons.
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.
Strassman
Andrew M
AM
Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA. Andrew.Strassman@bidmc.harvard.edu
Levy
Dan
D
D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics*; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008578:Meninges / Q000166:cytology*; D008881:Migraine Disorders / Q000188:drug therapy* / Q000503:physiopathology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology*; D012668:Trigeminal Ganglion / Q000166:cytology
D017366:Serotonin Receptor Agonists; D018170:Sumatriptan; D002118:Calcium