title: Sumatriptan inhibits TRPV1 channels in trigeminal neurons.
abstract: OBJECTIVE
  To understand a possible role for transient potential receptor vanilloid 1 (TRPV1) ion channels in sumatriptan relief of pain mediated by trigeminal nociceptors.
  
  
  BACKGROUND
  TRPV1 channels are expressed in small nociceptive sensory neurons. In dorsal root ganglia, TRPV1-containing nociceptors mediate certain types of inflammatory pain. Neurogenic inflammation of cerebral dura and blood vessels in the trigeminal nociceptive system is thought to be important in migraine pain, but the ion channels important in transducing migraine pain are not known. Sumatriptan is an agent effective in treatment of migraine and cluster headache. We hypothesized that sumatriptan might modulate activity of TRPV1 channels found in the trigeminal nociceptive system.
  
  
  METHODS
  We used immunohistochemistry to detect the presence of TRPV1 channel protein, whole-cell recording in acutely dissociated trigeminal ganglia (TG) to detect functionality of TRPV1 channels, and whole-cell recording in trigeminal nucleus caudalis (TNC) to detect effects on release of neurotransmitters from trigeminal neurons onto second order sensory neurons. Effects specifically on TG neurons that project to cerebral dura were assessed by labeling dural nociceptors with DiI.
  
  
  RESULTS
  Immunohistochemistry demonstrated that TRPV1 channels are present in cerebral dura, in trigeminal ganglion, and in the TNC. Capsaicin, a TRPV1 agonist, produced depolarization and repetitive action potential firing in current clamp recordings, and large inward currents in voltage clamp recordings from acutely dissociated TG neurons, demonstrating that TRPV1 channels are functional in trigeminal neurons. Capsaicin increased spontaneous excitatory postsynaptic currents in neurons of layer II in TNC slices, showing that these channels have a physiological effect on central synaptic transmission. Sumatriptan (10 µM), a selective antimigraine drug, inhibited TRPV1-mediated inward currents in TG and capsaicin-elicited spontaneous excitatory postsynaptic currents in TNC slices. The same effects of capsaicin and sumatriptan were found in acutely dissociated DiI-labeled TG neurons innervating cerebral dura.
  
  
  CONCLUSIONS
  Our results build on previous work indicating that TRPV1 channels in trigeminal nociceptors play a role in craniofacial pain. Our findings that TRPV1 is inhibited by the specific antimigraine drug sumatriptan, and that TRPV1 channels are functional in neurons projecting to cerebral dura suggests a specific role for these channels in migraine or cluster headache.
authors.affiliation: Department of Neurology, Southern Illinois University School of Medicine, 500 South Preston St., Louisville, KY 40292, USA. mail@msevans.com
authors.forename: Miles Steven
authors.initials: MS
authors.lastname: Evans
authors.forename: Xiangying
authors.initials: X
authors.lastname: Cheng
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Jeffry
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Disney
authors.forename: Louis S
authors.initials: LS
authors.lastname: Premkumar
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002211:Capsaicin / Q000494:pharmacology; D002232:Carbocyanines; D004388:Dura Mater / Q000378:metabolism; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology*; D050916:TRPV Cation Channels / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000166:cytology*
chemical_list: D002232:Carbocyanines; D058825:Serotonin 5-HT1 Receptor Agonists; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C024286:3,3'-dioctadecylindocarbocyanine; D018170:Sumatriptan; D002211:Capsaicin