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. CONCLUSION: The findings suggest that capsaicin decreases both TTX-s and TTX-r INa(+) as a result of an increase in [Na(+)]i through TRPV1.
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. CONCLUSION: 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: David A Andersson; Clive Gentry; Lisa Alenmyr; Dan Killander; Simon E Lewis; Anders Andersson; Bernard Bucher; Jean-Luc Galzi; Olov Sterner; Stuart Bevan; Edward D Högestätt; Peter M Zygmunt Journal: Nat Commun Date: 2011-11-22 Impact factor: 14.919