PMID- 22289052
OWN - NLM
STAT- MEDLINE
DCOM- 20130510
LR  - 20211021
IS  - 1526-4610 (Electronic)
IS  - 0017-8748 (Print)
IS  - 0017-8748 (Linking)
VI  - 52
IP  - 5
DP  - 2012 May
TI  - Sumatriptan inhibits TRPV1 channels in trigeminal neurons.
PG  - 773-84
LID - 10.1111/j.1526-4610.2011.02053.x [doi]
AB  - 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 microM), 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. 
      CONCLUSION: 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.
CI  - (c) 2012 American Headache Society.
FAU - Evans, Miles Steven
AU  - Evans MS
AD  - Department of Neurology, Southern Illinois University School of Medicine, 500 
      South Preston St., Louisville, KY 40292, USA. mail@msevans.com
FAU - Cheng, Xiangying
AU  - Cheng X
FAU - Jeffry, Joseph A
AU  - Jeffry JA
FAU - Disney, Kimberly E
AU  - Disney KE
FAU - Premkumar, Louis S
AU  - Premkumar LS
LA  - eng
GR  - R01 DA028017/DA/NIDA NIH HHS/United States
GR  - R01 DA028017-04/DA/NIDA NIH HHS/United States
GR  - DA028017/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120130
PL  - United States
TA  - Headache
JT  - Headache
JID - 2985091R
RN  - 0 (Carbocyanines)
RN  - 0 (Serotonin 5-HT1 Receptor Agonists)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (Trpv1 protein, rat)
RN  - 40957-95-7 (3,3'-dioctadecylindocarbocyanine)
RN  - 8R78F6L9VO (Sumatriptan)
RN  - S07O44R1ZM (Capsaicin)
SB  - IM
MH  - Action Potentials/drug effects
MH  - Analysis of Variance
MH  - Animals
MH  - Animals, Newborn
MH  - Capsaicin/pharmacology
MH  - Carbocyanines
MH  - Dura Mater/metabolism
MH  - Electric Stimulation
MH  - Excitatory Postsynaptic Potentials/drug effects
MH  - Female
MH  - Gene Expression Regulation/*drug effects
MH  - In Vitro Techniques
MH  - Male
MH  - Neurons/*drug effects
MH  - Patch-Clamp Techniques
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin 5-HT1 Receptor Agonists/*pharmacology
MH  - Sumatriptan/*pharmacology
MH  - TRPV Cation Channels/*metabolism
MH  - Trigeminal Ganglion/*cytology
PMC - PMC3342425
MID - NIHMS337490
COIS- Conflicts of Interest: No conflict for any author
EDAT- 2012/02/01 06:00
MHDA- 2013/05/11 06:00
PMCR- 2013/05/01
CRDT- 2012/02/01 06:00
PHST- 2012/02/01 06:00 [entrez]
PHST- 2012/02/01 06:00 [pubmed]
PHST- 2013/05/11 06:00 [medline]
PHST- 2013/05/01 00:00 [pmc-release]
AID - 10.1111/j.1526-4610.2011.02053.x [doi]
PST - ppublish
SO  - Headache. 2012 May;52(5):773-84. doi: 10.1111/j.1526-4610.2011.02053.x. Epub 2012 
      Jan 30.