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Evodiamine suppresses capsaicin-induced thermal hyperalgesia through activation and subsequent desensitization of the transient receptor potential V1 channels.
J Nat Med. 2016 Jan; 70(1):1-7.JN

Abstract

Evodiae fructus (EF), a fruit of Evodia rutaecarpa Bentham, has long been used as an analgesic drug in traditional Chinese and Japanese medicine. However, the underlying molecular mechanism of its pharmacological action is unclear. Here, using calcium imaging, whole-cell patch-clamp recording, and behavioral analysis, we investigated the pharmacological action of EF and its principal compound, evodiamine, on the transient receptor potential (TRP) V1 channels. Dorsal root ganglion (DRG) neurons and TRPV1- or TRPA1-transfected human embryonic kidney-derived (HEK) 293 cells were used for calcium imaging or whole-cell patch-clamp recording. Twenty male adult Sprague-Dawley rats were used for the capsaicin-induced thermal hyperalgesia behavioral analyses. We found that evodiamine induced significant increases in intracellular calcium and robust inward currents in a subpopulation of isolated rat DRG neurons, most of which were also sensitive to capsaicin. The effect of evodiamine was completely blocked by capsazepine, a competitive antagonist of TRPV1. Evodiamine induced significant inward currents in TRPV1-, but not TRPA1-transfected HEK293 cells. Pretreatment with evodiamine reduced capsaicin-induced currents significantly. Furthermore, the in vivo pre-treatment of evodiamine suppressed thermal hyperalgesia induced by intraplantar injection of capsaicin in rats. These results identify that the analgesic effect of EF and evodiamine may be due to the activation and subsequent desensitization of TRPV1 in sensory neurons.

Authors+Show Affiliations

Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo, 6508530, Japan.Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo, 6508530, Japan. Traditional Medicine Research Center, Chinese Medicine Confucius Institute, Hyogo College of Medicine, Kobe, Hyogo, 6508530, Japan.Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo, 6508530, Japan. FALCO Pharmacies Ltd., Kyoto, Japan.Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo, 6508530, Japan.Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo, 6508530, Japan.Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo, 6508530, Japan.Traditional Medicine Research Center, Chinese Medicine Confucius Institute, Hyogo College of Medicine, Kobe, Hyogo, 6508530, Japan. Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya, Hyogo, 6638501, Japan.Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo, 6508530, Japan. ydai@huhs.ac.jp. Traditional Medicine Research Center, Chinese Medicine Confucius Institute, Hyogo College of Medicine, Kobe, Hyogo, 6508530, Japan. ydai@huhs.ac.jp. Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya, Hyogo, 6638501, Japan. ydai@huhs.ac.jp.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26188960

Citation

Iwaoka, Emiko, et al. "Evodiamine Suppresses Capsaicin-induced Thermal Hyperalgesia Through Activation and Subsequent Desensitization of the Transient Receptor Potential V1 Channels." Journal of Natural Medicines, vol. 70, no. 1, 2016, pp. 1-7.
Iwaoka E, Wang S, Matsuyoshi N, et al. Evodiamine suppresses capsaicin-induced thermal hyperalgesia through activation and subsequent desensitization of the transient receptor potential V1 channels. J Nat Med. 2016;70(1):1-7.
Iwaoka, E., Wang, S., Matsuyoshi, N., Kogure, Y., Aoki, S., Yamamoto, S., Noguchi, K., & Dai, Y. (2016). Evodiamine suppresses capsaicin-induced thermal hyperalgesia through activation and subsequent desensitization of the transient receptor potential V1 channels. Journal of Natural Medicines, 70(1), 1-7. https://doi.org/10.1007/s11418-015-0929-1
Iwaoka E, et al. Evodiamine Suppresses Capsaicin-induced Thermal Hyperalgesia Through Activation and Subsequent Desensitization of the Transient Receptor Potential V1 Channels. J Nat Med. 2016;70(1):1-7. PubMed PMID: 26188960.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evodiamine suppresses capsaicin-induced thermal hyperalgesia through activation and subsequent desensitization of the transient receptor potential V1 channels. AU - Iwaoka,Emiko, AU - Wang,Shenglan, AU - Matsuyoshi,Nobuyuki, AU - Kogure,Yoko, AU - Aoki,Shunji, AU - Yamamoto,Satoshi, AU - Noguchi,Koichi, AU - Dai,Yi, Y1 - 2015/07/19/ PY - 2015/04/21/received PY - 2015/07/05/accepted PY - 2015/7/20/entrez PY - 2015/7/21/pubmed PY - 2016/7/28/medline KW - Desensitization KW - Evodiamine KW - Goshuyu KW - Hyperalgesia KW - TRPV1 KW - Wu-Zhu-Yu SP - 1 EP - 7 JF - Journal of natural medicines JO - J Nat Med VL - 70 IS - 1 N2 - Evodiae fructus (EF), a fruit of Evodia rutaecarpa Bentham, has long been used as an analgesic drug in traditional Chinese and Japanese medicine. However, the underlying molecular mechanism of its pharmacological action is unclear. Here, using calcium imaging, whole-cell patch-clamp recording, and behavioral analysis, we investigated the pharmacological action of EF and its principal compound, evodiamine, on the transient receptor potential (TRP) V1 channels. Dorsal root ganglion (DRG) neurons and TRPV1- or TRPA1-transfected human embryonic kidney-derived (HEK) 293 cells were used for calcium imaging or whole-cell patch-clamp recording. Twenty male adult Sprague-Dawley rats were used for the capsaicin-induced thermal hyperalgesia behavioral analyses. We found that evodiamine induced significant increases in intracellular calcium and robust inward currents in a subpopulation of isolated rat DRG neurons, most of which were also sensitive to capsaicin. The effect of evodiamine was completely blocked by capsazepine, a competitive antagonist of TRPV1. Evodiamine induced significant inward currents in TRPV1-, but not TRPA1-transfected HEK293 cells. Pretreatment with evodiamine reduced capsaicin-induced currents significantly. Furthermore, the in vivo pre-treatment of evodiamine suppressed thermal hyperalgesia induced by intraplantar injection of capsaicin in rats. These results identify that the analgesic effect of EF and evodiamine may be due to the activation and subsequent desensitization of TRPV1 in sensory neurons. SN - 1861-0293 UR - https://www.unboundmedicine.com/medline/citation/26188960/Evodiamine_suppresses_capsaicin_induced_thermal_hyperalgesia_through_activation_and_subsequent_desensitization_of_the_transient_receptor_potential_V1_channels_ L2 - https://dx.doi.org/10.1007/s11418-015-0929-1 DB - PRIME DP - Unbound Medicine ER -