title: Capsaicin indirectly suppresses voltage-gated Na+ currents through TRPV1 in rat dorsal root ganglion neurons.
abstract: BACKGROUND
  Capsaicin is used to treat a variety of types of chronic pain, including arthritis and trigeminal neuralgia. Although the cellular effects of capsaicin have been widely studied, little is known about the effects of capsaicin on intracellular sodium ([Na(+)]i) concentrations and voltage-gated Na(+) currents (INa(+)) in nociceptive afferent neurons. Therefore, in this study we sought to characterize the effect of capsaicin on tetrodotoxin-sensitive (TTX-s) and resistant (TTX-r) INa(+).
  
  
  METHODS
  The effects of capsaicin on INa(+) in rat dorsal root ganglion neurons were studied for both TTX-s and TTX-r components using whole-cell patch-clamp techniques and intracellular sodium imaging.
  
  
  RESULTS
  In both TTX-s and TTX-r INa(+) of capsaicin-sensitive neurons, capsaicin (0.1 to 10 μM) reduced inward currents in a dose-dependent manner. Capsaicin induced a hyperpolarization shift in the steady-state inactivation curves. SB366791 (10 μM), a potent and selective transient receptor potential vanilloid member1 (TRPV1) antagonist, significantly attenuated the reduction in INa(+). Capsaicin induced an increase in the [Na(+)]i, and SB366791 (10 μM) significantly reduced the [Na(+)]i increase. An increase in [Na(+)]i with gramicidin also dependently suppressed INa(+) and induced a hyperpolarization shift in the steady-state inactivation curves by increasing the [Na(+)]i.
  
  
  CONCLUSIONS
  The findings suggest that capsaicin decreases both TTX-s and TTX-r INa(+) as a result of an increase in [Na(+)]i through TRPV1.
authors.affiliation: Department of Anaesthesiology and Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan. pirotann@med.miyazaki-u.ac.j
authors.forename: Shin
authors.initials: S
authors.lastname: Onizuka
authors.forename: Tetsu
authors.initials: T
authors.lastname: Yonaha
authors.forename: Ryuji
authors.initials: R
authors.lastname: Tamura
authors.forename: Nobuko
authors.initials: N
authors.lastname: Hosokawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kawasaki
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kashiwada
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Shirasaka
authors.forename: Isao
authors.initials: I
authors.lastname: Tsuneyoshi
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000502:physiology*; D050916:TRPV Cation Channels / Q000502:physiology*
chemical_list: D026941:Sodium Channel Blockers; D015222:Sodium Channels; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D002211:Capsaicin