Inhibition of acid-sensing ion channels by levo-tetrahydropalmatine in rat dorsal root ganglion neurons.

Abstract

Levo-tetrahydropalmatine (l-THP), a main bioactive Chinese herbal constituent from the genera Stephania and Corydalis, has been in use in clinical practice for years in China as a traditional analgesic agent. However, the mechanism underlying the analgesic action of l-THP is poorly understood. This study shows that l-THP can exert an inhibitory effect on the functional activity of native acid-sensing ion channels (ASICs), which are believed to mediate pain caused by extracellular acidification. l-THP dose dependently decreased the amplitude of proton-gated currents mediated by ASICs in rat dorsal root ganglion (DRG) neurons. l-THP shifted the proton concentration-response curve downward, with a decrease of 40.93% ± 8.45% in the maximum current response to protons, with no significant change in the pH0.5 value. Moreover, l-THP can alter the membrane excitability of rat DRG neurons to acid stimuli. It significantly decreased the number of action potentials and the amplitude of the depolarization induced by an extracellular pH drop. Finally, peripherally administered l-THP inhibited the nociceptive response to intraplantar injection of acetic acid in rats. These results indicate that l-THP can inhibit the functional activity of ASICs in dissociated primary sensory neurons and relieve acidosis-evoked pain in vivo, which for the first time provides a novel peripheral mechanism underlying the analgesic action of l-THP.

• Authors: Ting-Ting Liu, Zu-Wei Qu, Chun-Yu Qiu, Fang Qiu, Cuixia Ren, Xiong Gan, Fang Peng, Wang-Ping Hu
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 93 Issue 2 Pg. 333-9 (Feb 2015) ISSN: 1097-4547 [Electronic] United States
• PMID: 25395088 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• Acid Sensing Ion Channel Blockers
• Acid Sensing Ion Channels
• Berberine Alkaloids
• Calcium Channel Blockers
• Protons
• tetrahydropalmatine

Topics

• Acid Sensing Ion Channel Blockers (pharmacology)
• Acid Sensing Ion Channels (metabolism)
• Animals
• Berberine Alkaloids (pharmacology)
• Calcium Channel Blockers (pharmacology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Ganglia, Spinal (cytology)
• Hydrogen-Ion Concentration
• Male
• Membrane Potentials (drug effects)
• Neurons (drug effects)
• Pain (chemically induced, prevention & control)
• Pain Measurement (drug effects)
• Patch-Clamp Techniques
• Protons (adverse effects)
• Rats
• Rats, Sprague-Dawley