Experimental Research Article

Korean J Pain 2021; 34(3): 262-270

Published online July 1, 2021 https://doi.org/10.3344/kjp.2021.34.3.262

Copyright © The Korean Pain Society.

Ononis spinosa alleviated capsaicin-induced mechanical allodynia in a rat model through transient receptor potential vanilloid 1 modulation

Sahar Majdi Jaffal1 , Belal Omar Al-Najjar2,3 , Manal Ahmad Abbas3,4

1Department of Biological Sciences, Faculty of Science, The University of Jordan, Amman, Jordan
2Department of Pharmaceutical Sciences, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan
3Pharmacological and Diagnostic Research Center, Al-Ahliyya Amman University, Amman, Jordan
4Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman, Jordan

Correspondence to:Sahar Majdi Jaffal
Department of BiologicalSciences, Faculty of Science, The University of Jordan, Amman 11942, Jordan
Tel: +962787924254
Fax: +96265300253
E-mail: sjaff333@gmail.com

Handling Editor: Sang Hun Kim

Received: January 2, 2021; Revised: April 7, 2021; Accepted: April 8, 2021

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background: Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel implicated in pain sensation in response to heat, protons, and capsaicin (CAPS). It is well established that TRPV1 is involved in mechanical allodynia. This study investigates the effect of Ononis spinosa (Fabaceae) in CAPS-induced mechanical allodynia and its mechanism of action.
Methods: Mechanical allodynia was induced by the intraplantar (ipl) injection of 40 μg CAPS into the left hind paw of male Wistar rats. Animals received an ipl injection of 100 μg O. spinosa methanolic leaf extract or 2.5% diclofenac sodium 20 minutes before CAPS injection. Paw withdrawal threshold (PWT) was measured using von Frey filament 30, 90, and 150 minutes after CAPS injection. A molecular docking tool, AutoDock 4.2, was used to study the binding energies and intermolecular interactions between O. spinosa constituents and TRPV1 receptor.
Results: The ipsilateral ipl injection of O. spinosa before CAPS injection increased PWT in rats at all time points. O. spinosa decreased mechanical allodynia by 5.35-fold compared to a 3.59-fold decrease produced by diclofenac sodium. The ipsilateral pretreatment with TRPV1 antagonist (300 μg 4-[3-Chloro-2-pyridinyl]- N-[4-[1,1-dimethylethyl] phenyl]-1-piperazinecarboxamide [BCTC]) as well as the β2-adrenoreceptor antagonist (150 μg butoxamine) attenuated the action of O. spinosa. Depending on molecular docking results, the activity of the extract could be attributed to the bindings of campesterol, stigmasterol, and ononin compounds to TRPV1.
Conclusions: O. spinosa alleviated CAPS-induced mechanical allodynia through 2 mechanisms: the direct modulation of TRPV1 and the involvement of β2 adrenoreceptor signaling.

Keywords: Butoxamine, Capsaicin, Fabaceae, Hyperalgesia, Molecular Docking Simulation, Neuralgia, Ononis, Pain, Stigmasterol, TRPV Cation Channels.