• Yan Zhang, Chaoran Wang, Lien Wang, Gregory Scott Parks, Xiuli Zhang, Zhimou Guo, Yanxiong Ke, Kang-Wu Li, Mi Kyeong Kim, Benjamin Vo, Emiliana Borrelli, Guangbo Ge, Ling Yang, Zhiwei Wang, M Julia Garcia-Fuster, Z David Luo, Xinmiao Liang, and Olivier Civelli.
• Department of Pharmacology, University of California, Irvine, Irvine, CA 92697, USA.
• Curr. Biol. 2014 Jan 20; 24 (2): 117-23.

BackgroundCurrent pain management is limited, in particular, with regard to chronic pain. In an attempt to discover novel analgesics, we combined the approach developed to characterize traditional Chinese medicine (TCM), as part of the "herbalome" project, with the reverse pharmacology approach aimed at discovering new endogenous transmitters and hormones.ResultsIn a plant used for centuries for its analgesic properties, we identify a compound, dehydrocorybulbine (DHCB), that is effective at alleviating thermally induced acute pain. We synthesize DHCB and show that it displays moderate dopamine receptor antagonist activities. By using selective pharmacological compounds and dopamine receptor knockout (KO) mice, we show that DHCB antinociceptive effect is primarily due to its interaction with D2 receptors, at least at low doses. We further show that DHCB is effective against inflammatory pain and injury-induced neuropathic pain and furthermore causes no antinociceptive tolerance.ConclusionsOur study casts DHCB as a different type of analgesic compound and as a promising lead in pain management.Copyright © 2014 Elsevier Ltd. All rights reserved.

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