Anti-nociceptive mechanisms of Melilotus officinalis Linn. ethanoic extract in mice: Involvement of opioidergic, nitrergic and muscarinic receptors

Document Type : Research Paper

Authors

1 Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran

2 Department of Clinical Sciences, Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran

3 Division of Physiology, Department of Basic Sciences, Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran

Abstract

Background and Objective: Pain is a physiologic protective function with regard to external or internal harmful stimulus or tissue damage. The aim of the current study was to determine anti-nociceptive activity of Melilotus officinalis (Linn.) extract on formalin-induced pain in mice.
Materials and Methods: In experiment 1, adult male mice were injected (i.p) with saline, ethanoic extract of Melilotus officinalis (Linn.) (EEMO) (100, 200 and 400 mg/kg) or morphine (5 mg/kg). In experiment 2, mice were injected with saline, EEMO (400 mg/kg), naloxone (2 mg/kg) and co-injection of EEMO (400 mg/kg) + naloxone (2 mg/kg). In experiment 3, animal received i.p injection of saline, EEMO (400 mg/kg), L-NAME (10 mg/kg) and EEMO (400 mg/kg) + L-NAME (10 mg/kg). In experiment 4, mice were injected (i.p) with saline, EEMO (400 mg/kg), atropine (1 mg/kg) and co-administration of EEMO (400 mg/kg) + atropine (1 mg/kg). Then, the time spent for paw licking was determined the in first and second phase after formalin injection. Then, licking and biting time of the injected paw was recorded after formalin injection in first and second phases.   
Results: According to the results, EEMO in a dose dependent manner significantly diminished licking and biting time of injected paw (pain response) in comparison with the control group (P<0.05). Co-injection of the naloxone + EEMO significantly amplified pain response compared to the EEMO group (P<0.05). Co-injection of the L-NAME + EEMO significantly decreased pain response in comparison with the EEMO group (P<0.05). Pretreatment with atropine significantly enhanced pain response in comparison with the EEMO group (P<0.05).
Conclusion: These findings suggest that anti-nociceptive activity of the EEMO is mediated via opioidergic, nitrergic and muscarinergic systems in mice.

Keywords


 Mahdian Dehkordi F, Kaboutari J, Zendehdel M, Javdani M. The antinociceptive effect of artemisinin on the inflammatory pain and role of GABAergic and opioidergic systems. The Korean Journal of Pain 2019;32(3):160.
de Oliveira JRG, Ferraz CAA, Silva JC, de Oliveira AP, Diniz TC, Silva MG, et al. Antinociceptive Effect of the Essential Oil from Croton conduplicatus Kunth (Euphorbiaceae). Molecules 2017 30;22(6):900.
Grace PM, Hutchinson MR, Maier SF, Watkins LR. Pathological pain and the neuroimmune interface. Nature Reviews. Immunology 2014; 14(4):217-31.
Fathi M, Hosseinmardi N, Rohampour K, Janahmadi M, Sonboli A, Zaringhalam J. Anti-nociceptive effect of Tanacetum Fisherae on formalin-induced inflammatory pain in rats. Physiology and Pharmacology 2016;20(3):189-96.
Galvão GM, Florentino IF, Sanz G, Vaz BG, Lião LM, Sabino JR, Cardoso CS, da Silva DP, Costa EA, Silva AL, da Silva AC. Anti-inflammatory and antinociceptive activity profile of a new lead compound–LQFM219. International Immunopharmacology 2020;88:106893.
Al-Snafi AE. Chemical constituents and pharmacological effects of Melilotus Officinalis-A review. IOSR Journal of Pharmacy 2020;10(1):26-36.
Chorepsima S, Tentolouris K, Dimitroulis D, Tentolouris N. Melilotus: Contribution to wound healing in the diabetic foot. Journal of Herbal Medicine 2013;3(3):81-6.
Jaiswal AK, Gupta S, Abu-Ghannam N. Kinetic evaluation of colour, texture, polyphenols and antioxidant capacity of Irish York cabbage after blanching treatment. Food Chemistry 2012;131(1):63-72.
Jasicka-Misiak I, Makowicz E, Stanek N. Polish yellow sweet clover (Melilotus officinalis L.) honey, chromatographic fingerprints, and chemical markers. Molecules 2017;22(1):138.
Heydari MR, Najafi F, Asadipour A, Ansari M, Zahedi MJ, Vahedian M. Analgesic and ulcerogenic effect of Methanolic extract of Melilotus Officinalis. Journal of Kerman University of Medical Sciences 2018; (4): 210 -219.
De Almeida Barros TA, De Freitas LA, Filho JM, Nunes XP, Giulietti AM, De Souza GE, Dos Santos RR, Soares MB, Villarreal CF. Antinociceptive and anti‐inflammatory properties of 7‐hydroxycoumarin in experimental animal models: potential therapeutic for the control of inflammatory chronic pain. Journal of Pharmacy and Pharmacology 2010;62(2):205-13.
Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain 1983: 16(2):109-110.), pp. 109- 10.
Kim DH, Sun20g B, Kang YJ, Jang JY, Hwang SY, Lee Y, Kim M, Im E, Yoon JH, Kim CM, Chung HY. Anti-inflammatory effects of betaine on AOM/DSS induced colon tumorigenesis in ICR male mice. International Journal of Oncology 2014;45(3):1250-6.
Stefanović OD, Tešić JD, Čomić LR. Melilotus albus and Dorycnium herbaceum extracts as source of phenolic compounds and their antimicrobial, antibiofilm, and antioxidant potentials. Journal of Food and Drug Analysis 2015;23(3):417-24.
Hunskaar S, Hole K. The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain 1987;30(1):103-14.
Abbott FV, Bonder M. Options for management of acute pain in the rat. Vet Record 1997;140: 553-57.
Hajhashemi V, Sajjadi SE, Zomorodkia M. Antinociceptive and anti-inflammatory activities of Bunium persicum essential oil, hydroalcoholic and polyphenolic extracts in animal models. Pharmaceutical Biology 2011;49(2):146-51.
Zendehdel M, Torabi Z, Hassanpour S. Antinociceptive mechanisms of Bunium persicum essential oil in the mouse writhing test: role of opioidergic and histaminergic systems. Veterinarni Medicina 2015;60(2):63-70.
Hassanpour S, Rezaei H, Razavi SM. 2020. Anti-nociceptive and antioxidant activity of Betaine on Formalin- and Writhing tests induced pain in mice. Behavioural Brain Research 2020; 15;390:112699.390: 112699.
Shi GN, Liu YL, Lin HM, Yang SL, Feng YL, Reid PF, Qin ZH. Involvement of cholinergic system in suppression of formalin-induced inflammatory pain by cobratoxin. Acta Pharmacologica Sinica 2011;32(10):1233-1238.
Labuz D, Celik MÖ, Zimmer A, Machelska H. Distinct roles of exogenous opioid agonists and endogenous opioid peptides in the peripheral control of neuropathy-triggered heat pain. Scientific Reports 2016;6:32799.
Markus J, Wang D, Kim YJ, Ahn S, Mathiyalagan R, Wang C, Yang DC. Biosynthesis, characterization, and bioactivities evaluation of silver and gold nanoparticles mediated by the roots of Chinese herbal Angelica pubescens Maxim. Nanoscale Research Letters 2017;12(1):46.
Silva, K., Gritsenko, K., & Wahezi, S. E. (2017). Animal Models of Nociception and Pain. In Pain Medicine (pp. 23-24). Springer, Cham.
Park SH, Sim YB, Kang YJ, Kim SS, Kim CH, Kim SJ, Lim SM, Suh HW. Antinociceptive profiles and mechanisms of orally administered coumarin in mice. Biological and Pharmaceutical Bulletin 2013;36(6):925-30.
Li R, Dang S, Yao M, Zhao C, Zhang W, Cui J, Wang J, Wen A. Osthole alleviates neuropathic pain in mice by inhibiting the P2Y1-receptor-dependent JNK signaling pathway. Aging  2020;12(9):7945.
De Feo M, Paladini A, Ferri C, Carducci A, Del Pinto R, Varrassi G, Grassi D. Anti-Inflammatory and Anti-Nociceptive Effects of Cocoa: A Review on Future Perspectives in Treatment of Pain. Pain and Therapy 2020 ;9(1):231-240.
Chen Y, Boettger MK, Reif A, Schmitt A, Üçeyler N, Sommer C. Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice. Molecular Pain 2010;6(1):13.
Gonçalves GM, Marinho DG, Almança CC, Marinho BG. Anti-nociceptive and anti-oedematogenic properties of the hydroethanolic extract of Sidastrum micranthum leaves in mice. Revista Brasileira de Farmacognosia 2013;23(5):836-43.
Liu YT, Gong PH, Xiao FQ, Shao S, Zhao DQ, Yan MM, Yang XW. Chemical constituents and antioxidant, anti-inflammatory and anti-tumor activities of melilotus officinalis (linn.) pall. Molecules 2018;23(2):271.
De Lima FO, Nonato FR, Couto RD, Barbosa Filho JM, Nunes XP, Ribeiro dos Santos R, Soares MB, Villarreal CF. Mechanisms involved in the antinociceptive effects of 7-hydroxycoumarin. Journal of Natural Products 2011;74(4):596-602.