Euphorbia bicolor (Euphobiaceae) Latex Extract Induces Antinociception and Analgesia in a Rat Inflammatory Pain Model
Authors: Basu Paramita , Harris Taylor , Tongkhuya Sirima , Riley Angela , Wojtaszek Jennie , Granger John , Averitt Dayna L. , Maier Camelia 
Published: June 2021

Cancer patients or those suffering form severe injury are treated with opioids and nonsteroidal anti‐inflammatory drugs (NSAIDs) to relieve pain. Opioids cause addiction and tolerance mediated by the central nervous system, while NSAIDs cause gastrointestinal disorders. These side effects underscore the search for plant bioactive compounds for use in pain treatment. One potential target for pain management is through the transient receptor potential V1 ion channel (TRPV1). Activation of TRPV1 induces calcitonin gene‐related peptide (CGRP) release, which contributes to peripheral sensitization and hyperalgesia. Potent agonists such as capsaicin and resiniferatoxin (RTX) target TRPV1 and induce peripheral analgesia via receptor desensitization. Resiniferatoxin was identified in Euphorbia resinifera latex. The present work studies the analgesic properties of Euphorbia bicolor (Euphorbiaceae), species native to the Southern United States and related to exotic E. resinifera. It was expected that E. bicolor latex extract, similarly to that of E. resinifera, would contain phytochemicals that attenuate nociceptive signaling in cultured sensory neurons and evoke analgesia in an animal model of inflammatory pain. Cultured rat trigeminal sensory neurons were treated with E. bicolor latex (0, 12.5, 25, 50, 100, 300 μg/ml) or vehicle for 15 minutes followed by stimulation with capsaicin (50 nM) and CGRP was quantified by ELISA. In another experiment, rats received an intraplantar injection of complete Freund's adjuvant to induce inflammatory pain and 24 hours later inflamed paws were treated with E. bicolor extract (300 μg/ml in 100 μl) or vehicle and latencies were reassessed at 1, 3, 6, 24, 48, and 72 hours, then weekly for 4 weeks. A subset of rats was pretreated with the TRPV1 antagonist capsazepine (100 μM) or vehicle prior to E. bicolor latex extract injection. These experiments resulted in significantly reduced capsaicin‐evoked CGRP release and significantly reduced inflammatory thermal hyperalgesia within 6 hours post E. bicolor latex extract (50 and 100 μg/ml) injections that lasted at least 24 hours. Capsazepine prevented analgesia indicating that TRPV1 may be involved in pain modulation by latex extract. Latex phytochemicals were analyzed by UPLC‐ESI‐MS/MS performed on a Waters Acquity UPLC coupled with electrospray ionization Xevo TQD triple quadrupole mass spectrometer operated in positive ionization mode. Chromatographic analyte separations were carried out using a gradient mobile phase consisting of (A) 0.1% formic acid, 10 mM ammonium formate and (B) 0.1% formic acid in acetonitrile (B) under linear gradient conditions (A:B % v/v, 0 min: 95:5; 9 min: 60:40; 10 min: 95:5) at 0.4 mL/min flow rate. Ion detection was performed in the multiple‐reaction monitoring (MRM) mode by monitoring the transition pairs. Several compounds, among those abietic acid, biochanin A, chalcone, coumestrol, daidzein, genistein, ingenol angelate, kaempferol, naringenin, quercetin, RTX, and rutin were identified in E. bicolor latex extract. Future work will focus on determining the compounds or mixture of compounds that contribute to the analgesic properties of E. bicolor latex and their mechanism of actions. E. bicolor latex phytochemicals may provide novel, non‐narcotic analgesics that could act on peripheral nervous system, thus avoiding the negative side effects exerted via the central nervous system.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.