The Korean Journal of Pain

The Korean Pain Society (대한통증학회)
권호 표지
DOI QR코드

DOI QR Code

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

  • Jaffal, Sahar Majdi (Department of Biological Sciences, Faculty of Science, The University of Jordan) ;
  • Al-Najjar, Belal Omar (Department of Pharmaceutical Sciences, Faculty of Pharmacy, Al-Ahliyya Amman University) ;
  • Abbas, Manal Ahmad (Pharmacological and Diagnostic Research Center, Al-Ahliyya Amman University)
  • Received : 2021.01.02
  • Accepted : 2021.04.08
  • Published : 2021.07.01
Download PDF
⟨ Previous Next ⟩

Abstract

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 ㎍ CAPS into the left hind paw of male Wistar rats. Animals received an ipl injection of 100 ㎍ 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 ㎍ 4-[3-Chloro-2-pyridinyl]-N-[4-[1,1-dimethylethyl] phenyl]-1-piperazinecarboxamide [BCTC]) as well as the β2-adrenoreceptor antagonist (150 ㎍ 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

Acknowledgement

This work was published with the support of Al-Ahliyya Amman University, Amman, Jordan. The authors acknowledge the University of Jordan.

References

  1. Moran MM, Szallasi A. Targeting nociceptive transient receptor potential channels to treat chronic pain: current state of the field. Br J Pharmacol 2018; 175: 2185-203. https://doi.org/10.1111/bph.14044
  2. Cavanaugh DJ, Chesler AT, Braz JM, Shah NM, Julius D, Basbaum AI. Restriction of transient receptor potential vanilloid-1 to the peptidergic subset of primary afferent neurons follows its developmental downregulation in nonpeptidergic neurons. J Neurosci 2011; 31: 10119-27. https://doi.org/10.1523/JNEUROSCI.1299-11.2011
  3. Gilchrist HD, Allard BL, Simone DA. Enhanced withdrawal responses to heat and mechanical stimuli following intraplantar injection of capsaicin in rats. Pain 1996; 67: 179-88. https://doi.org/10.1016/0304-3959(96)03104-1
  4. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997; 389: 816-24. https://doi.org/10.1038/39807
  5. Julius D. TRP channels and pain. Annu Rev Cell Dev Biol 2013; 29: 355-84. https://doi.org/10.1146/annurev-cellbio-101011-155833
  6. Alsalem M, Wong A, Millns P, Arya PH, Chan MS, Bennett A, et al. The contribution of the endogenous TRPV1 ligands 9-HODE and 13-HODE to nociceptive processing and their role in peripheral inflammatory pain mechanisms. Br J Pharmacol 2013; 168: 1961-74. https://doi.org/10.1111/bph.12092
  7. Wongrakpanich S, Wongrakpanich A, Melhado K, Rangaswami J. A comprehensive review of non-steroidal antiinflammatory drug use in the elderly. Aging Dis 2018; 9: 143-50. https://doi.org/10.14336/AD.2017.0306
  8. Al-Eisawi DMH. Field guide to wild flowers of Jordan and neighbouring countries. Amman, Jordan Press Foundation. 1998.
  9. Al-Snafi AE. The traditional uses, constituents and pharmacological effects of Ononis spinosa. IOSR J Pharm 2020; 10: 53-9.
  10. Yolmaz BS, Ozbek H, Citoglu GS, Ugras S, Bayram I, Erdogan E. Analgesic and hepatotoxic effects of Ononis spinosa L. Phytother Res 2006; 20: 500-3. https://doi.org/10.1002/ptr.1891
  11. Ergene Oz B, Saltan Iscan G, Kupeli Akkol E, Suntar I, Keles H, Bahadir Acikara O. Wound healing and anti-inflammatory activity of some Ononis taxons. Biomed Pharmacother 2017; 91: 1096-105. https://doi.org/10.1016/j.biopha.2017.05.040
  12. Al-Khalil S. A survey of plants used in Jordanian traditional medicine. Int J Pharmacogn 1995; 33: 317-23. https://doi.org/10.3109/13880209509065385
  13. Jaffal SM, Abbas MA. Antinociceptive action of Ononis spinosa leaf extract in mouse pain models. Acta Pol Pharm 2019; 76: 299-304.
  14. Lolignier S, Eijkelkamp N, Wood JN. Mechanical allodynia. Pflugers Arch 2015; 467: 133-9. https://doi.org/10.1007/s00424-014-1532-0
  15. Khasar SG, McCarter G, Levine JD. Epinephrine produces a beta-adrenergic receptor-mediated mechanical hyperalgesia and in vitro sensitization of rat nociceptors. J Neurophysiol 1999; 81: 1104-12. https://doi.org/10.1152/jn.1999.81.3.1104
  16. Nozadze I, Tsiklauri N, Gurtskaia G, Tsagareli MG. NSAIDs attenuate hyperalgesia induced by TRP channel activation. Data Brief 2016; 6: 668-73. https://doi.org/10.1016/j.dib.2015.12.055
  17. Ferrier J, Marchand F, Balayssac D. Assessment of mechanical allodynia in rats using the electronic von frey test. Bio Protoc 2016; 6: e1933.
  18. Gao Y, Cao E, Julius D, Cheng Y. TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action. Nature 2016; 534: 347-51. https://doi.org/10.1038/nature17964
  19. Walpole CS, Bevan S, Bovermann G, Boelsterli JJ, Breckenridge R, Davies JW, et al. The discovery of capsazepine, the first competitive antagonist of the sensory neuron excitants capsaicin and resiniferatoxin. J Med Chem 1994; 37: 1942-54. https://doi.org/10.1021/jm00039a006
  20. ACD/Labs. ACD/Structure Elucidator [computer program]. Version 2018.1 Toronto (ON).
  21. BIOVIA, Dassault Systemes. BIOVIA discovery studio visualizer [computer program]. Version 2002-2021 San Diego (CA).
  22. Abbas MA, Kandil YI, Abbas MM. Efficacy of extract from Ononis spinosa L. on ethanol-induced gastric ulcer in rats. J Tradit Chin Med 2021; 41: 270-5.
  23. Fricker PC, Gastreich M, Rarey M. Automated drawing of structural molecular formulas under constraints. J Chem Inf Comput Sci 2004; 44: 1065-78. https://doi.org/10.1021/ci049958u
  24. Stierand K, Maass PC, Rarey M. Molecular complexes at a glance: automated generation of two-dimensional complex diagrams. Bioinformatics 2006; 22: 1710-6. https://doi.org/10.1093/bioinformatics/btl150
  25. Matsushita Y, Manabe M, Kitamura N, Shibuya I. Adrenergic receptors inhibit TRPV1 activity in the dorsal root ganglion neurons of rats. PLoS One 2018; 13: e0191032. https://doi.org/10.1371/journal.pone.0191032
  26. Filippi A, Caruntu C, Gheorghe RO, Deftu A, Amuzescu B, Ristoiu V. Catecholamines reduce transient receptor potential vanilloid type 1 desensitization in cultured dorsal root ganglia neurons. J Physiol Pharmacol 2016; 67: 843-50.
  27. Jeske NA, Diogenes A, Ruparel NB, Fehrenbacher JC, Henry M, Akopian AN, et al. A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1. Pain 2008; 138: 604-16. https://doi.org/10.1016/j.pain.2008.02.022
  28. Chakraborty S, Elvezio V, Kaczocha M, Rebecchi M, Puopolo M. Presynaptic inhibition of transient receptor potential vanilloid type 1 (TRPV1) receptors by noradrenaline in nociceptive neurons. J Physiol 2017; 595: 2639-60. https://doi.org/10.1113/JP273455
  29. Nack ley AG, Tan KS, Fecho K, Flood P, Diatchenko L, Maixner W. Catechol-O-methyltransferase inhibition increases pain sensitivity through activation of both beta2- and beta3-adrenergic receptors. Pain 2007; 128: 199-208. https://doi.org/10.1016/j.pain.2006.09.022
  30. Zhu L, Zhao L, Qu R, Zhu HY, Wang Y, Jiang X, et al. Adrenergic stimulation sensitizes TRPV1 through upregulation of cystathionine β-synthetase in a rat model of visceral hypersensitivity. Sci Rep 2015; 5: 16109. https://doi.org/10.1038/srep16109
  31. Coutaux A, Adam F, Willer JC, Le Bars D. Hyperalgesia and allodynia: peripheral mechanisms. Joint Bone Spine 2005; 72: 359-71. https://doi.org/10.1016/j.jbspin.2004.01.010
  32. Benarroch EE. Dorsal horn circuitry: complexity and implications for mechanisms of neuropathic pain. Neurology 2016; 86: 1060-9. https://doi.org/10.1212/WNL.0000000000002478
  33. Al-Najjar BO. Synthesis, molecular docking and antioxidant evaluation of benzylidene ketone derivatives. Jordan J Biol Sci 2018; 11: 307-13.
  34. Benedec D, Vlase L, Oniga I, Toiu A, Tamas M, Tiperciuc B. Isoflavonoids from Glycyrrhiza sp. and Ononis spinosa. Farmacia 2012; 60: 615-20.
  35. Peres MTLP, Monache FD, Pizzolatti MG, Santos ARS, Beirith A, Calixto JB, et al. Analgesic compounds of Croton urucurana Baillon. Pharmaco-chemical criteria used in their isolation. Phytother Res 1998; 12: 209-11. https://doi.org/10.1002/(SICI)1099-1573(199805)12:3<209::AID-PTR215>3.0.CO;2-P
  36. Lee CW. Introduction of visceral pain model to test of visceral nociception in the rats. J Korean Pain Soc 1995; 8: 25-30.
  37. Julius D, Basbaum AI. Molecular mechanisms of nociception. Nature 2001; 413: 203-10. https://doi.org/10.1038/35093019
  38. Walker CIB, Oliveira SM, Tonello R, Rossato MF, da Silva Brum E, Ferreira J, et al. Anti-nociceptive effect of stigmasterol in mouse models of acute and chronic pain. Naunyn Schmiedebergs Arch Pharmacol 2017; 390: 1163-72. https://doi.org/10.1007/s00210-017-1416-x