Document Type : Original Article

Authors

1 PhD Candidate, Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

2 Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

Abstract

Thymoquinone (TQ) is the main biologically active substance of Nigella sativa (black seeds). It has anti-cancer, anti-inflammatory, anti-diabetic, anti-oxidative and anti-nociceptive properties. This study was aimed to explore the effect of TQ on acetic acid-induced visceral nociception. The central mechanisms of the effect of TQ were investigated using cannabinergic (AM251) and α2-adrenergic (yohimbine [Yoh]) antagonists. The lateral ventricle of the brain was cannulated for intracerebroventricular (ICV) injections. Visceral nociception was induced by intra-peritoneal (IP) injection of acetic acid (1.00% in a volume of 1.00 mL). Measuring the latency time to the first writhing appearance and counting the number of writhing in 5-min intervals for a period of 60 min were performed. Locomotor activity was determined using an open-field test. Oral administration (PO) of 2.50 and 10.00 mg kg-1 TQ increased the latency time to the first writhing appearance and decreased the number of writhing. The AM251 (5.00 µg per rat; ICV) and Yoh (5.00 µg per rat; ICV) partially prevented TQ (10.00 mg kg-1; PO)-induced anti-nociception. Locomotor activity was not altered by these treatments. The results of the present study showed that TQ had the ability to reduce visceral nociception caused by IP injection of acetic acid. The central mechanisms of this action of TQ might be partially mediated by cannabinergic and α2-adrenegic receptors.

Keywords

Main Subjects

  1. Collett B. Visceral pain: the importance of pain management services. Br J Pain 2013; 7(1): 6-7.
  2. Joshi SK, Gebhart GF. Visceral pain. Curr Rev Pain 2000; 4(6): 499-506.
  3. Lyubashina OA, Sivachenko IB, Panteleev SS. Supraspinal mechanisms of intestinal hypersensitivity. Cell Mol Neurobiol 2022; 42(2): 389-417.
  4. Yang M, Wang J, Yang C, et al. Oral administration of curcumin attenuates visceral hyperalgesia through inhibiting phosphorylation of TRPV1 in rat model of ulcerative colitis. Mol Pain 2017; 13: 17448069177 26416. doi: 10.1177/1744806917726416.
  5. Grothenhermen F. Cannabinoids. Curr Drug Targets CNS Neurol Disord 2005; 4(5): 507-530.
  6. Fraguas-Sánchez AI, Torres-Suárez AI. Medical use of cannabinoids. Drugs 2018; 78(16): 1665-1703.
  7. Finn DP, Haroutounian S, Hohmann AG, et al. Cannabinoids, endocannabinoid system, and pain: a review of preclinical studies. Pain 2021; 162(Suppl 1): S5-S25.
  8. Holland N, Robbins TW, Rowe JB. The role of noradrenaline in cognition and cognitive disorders. Brain 2021; 144(8): 2243-2256.
  9. Aldera H, AlQahtani OA, AlQahtani MA, et al. The neuronal cotransmission: mechanistic insights from the autonomic nervous system. Cureus 2023; 15(2): e35124. doi: 10.7759/cureus.35124.
  10. Gilsbach R, Hein L. Are the pharmacology and physiology of α2-adrenoceptors determined by α2-heteroreceptors and autoreceptors respectively? Br J Pharmacol 2012; 165(1): 90-102.
  11. Millan MJ. Descending control of pain. Prog Neurobiol 2002; 66(6): 355-474.
  12. Ahmad MF, Ahmad FA, Ashraf SA, et al. An updated knowledge of black seed (Nigella sativa Linn): review of phytochemical constituents and pharmacological properties. J Herb Med 2021; 25: 100404. doi: 10.1016/j.hermed.2020.100404.
  13. Khan MA, Afzal M. Chemical composition of Nigella sativa Linn: part 2 recent advances. Inflammo-pharmacology 2016; 24(2-3): 67-79.
  14. Sarkar C, Jamaddar S, Islam T, et al. Therapeutic pers-pectives of the black cumin component thymoquinone: a review. Food Funct 2021; 12(14): 6167-6213.
  15. Shad KF, Soubra W, Cordato DJ. The role of thymoquinone, a major constituent of Nigella sativa, in the treatment of inflammatory and infectious diseases. Clin Exp Pharmacol Physiol 2021; 48(11): 1445-1453.
  16. Verma R, Sartaj A, Qizilbash FF, et al. An overview of the neuropharmacological potential of thymoquinone and its targeted delivery prospects for CNS disorder. Curr Drug Metab 2022; 23(6): 447-459.
  17. Anaeigoudari A. Antidepressant and anti-nociceptive effects of Nigella sativa and its main constituent, thymoquinone: a literature review. Asian Pac J Trop Biomed 2022; 12(12): 495-503.
  18. Johnson AC, Meerveld BG-V. The pharmacology of visceral pain. Adv Pharmacol 2016; 75: 273-301.
  19. Farzaei MH, Bahramsoltani R, Abdollahi M, et al. The role of visceral hypersensitivity in irritable bowel syndrome: pharmacological targets and novel treatments. Neurogastroenterol Motil 2016; 22(4): 558-574.
  20. Safaei F, Tamaddonfard E, Nafisi S, et al. Effects of intraperitoneal and intracerebroventricular injection of cinnamaldehyde and yohimbine on blood glucose and serum insulin concentrations in ketamine-xylazune induced acute hyperglycemia. Vet Res Forum 2021; 12(2): 149-156.
  21. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 6th San Diego, USA: Academic Press 2007; 42-169.
  22. Kuzay D, Dileköz E, Özer Ç. Effects of thymoquinone in a rat model of reserpine-induced depression. Braz J Pharm Sci 2022; 58: e19847. doi: 10.1590/s2175-97902022e19847.
  23. Fraga D, Zanoni CIS, Zamprino AR, et al. Endo-cannabinoids, through opioids and prostaglandins, contribute to fever induced by key pyrogenic mediators. Brain Behav Immun 2016; 51: 204-211.
  24. Anbaraian F, Tamaddonfard E, Erfanparast A, et al. Cerebellar fastigial nucleus histamine and its H2 but not H1 receptors might inhibit acetic acid-induced visceral nociception and improve motor coordination in rats. Vet Res Forum 2023; 14(10): 549-557.
  25. Hajhashemi V, Ghannadi A, Jafarabadi H. Black cumin seed essential oil, as a potent analgesic and anti-inflammatory drug. Phytother Res 2004; 18(3): 195-199.
  26. Bashir MU, Qureshi HJ. Analgesic effect of Nigella sativa seeds extract on experimentally induced pain in albino mice. J Coll Physicians Surg Pak 2010; 20(7): 464-467.
  27. Alenezi SK. The ameliorative effect of thymoquinone on vincristine-induced peripheral neuropathy in mice by modulating cellular oxidative stress and cytokine. Life (Basel) 2022; 13(1): 101. doi: 10.3390/life13010101.
  28. Amin B, Taheri MMH, Hosseinzadeh H. Effects of intraperitoneal thymoquinone on chronic neuropathic pain in rats. Planta Med 2014; 80(15): 1269-1277.
  29. Micheli L, Di Cesare Mannelli L, Mosti E, et al. Antinociceptive action of thymoquinone-loaded liposomes in an in vivo model of tendinopathy. Pharmaceutics 2023; 15(5): 1516. doi: 10.3390/pharmaceutics15051516.
  30. Abdel-Fattah AM, Matsumoto K, Watanabe H. Antinociceptive effects of Nigella sativa oil and its major component, thymoquinone, in mice. Eur J Pharmacol 2000; 400(1): 89-97.
  31. Woodhams SG, Chapman V, Finn DP, et al. The cannabinoid system and pain. Neuropharmacology 2017; 124: 105-120.
  32. Bajic D, Monory K, Conrad A, et al. Cannabinoid receptor type 1 in the brain regulates the affective component of visceral pain in mice. Neuroscience 2018; 384: 397-405.
  33. Booker L, Naidu PS, Razdan RK, et al. Evaluation of prevalent phytocannabinoids in the acetic acid model of visceral nociception. Drug Alcohol Depend 2009; 105(1-2): 42-47.
  34. Aguiar DD, Gonzaga ACR, Teófilo ALH, et al. Curcumin induces peripheral antinociception by opioidergic and cannabinoidergic mechanism: Pharmacological evidence. Life Sci 2022; 293: 120279. doi: 10.1016/ j.lfs.2021.120279.
  35. Yimam M, O'Neal A, Horm T, et al. Antinociceptive and anti-Inflammatory properties of cannabidiol alone and in combination with standardized bioflavonoid composition. Med Food 2021; 24(9): 960-967.
  36. Pertovaara A. Noradrenergic pain modulation. Prog Neurobiol 2006; 80(2): 53-83.
  37. Korzeniewska-Rybicka I, Płaźnik A. Role of seretonergic and noradrenergic systems in a model of visceral pain. Pol J Pharmacol 2001; 53(5): 475-480.
  38. Wang T-X, Wu G-J, Jiang J-G. Natural products with analgesic effect from herbs and nutraceuticals used in traditional Chinese medicines. Curr Mol Med 2020; 20(6): 461-483.
  39. Ishola IO, Oreagba IA, OkekeOgochukwu N, et al. Analgesic and anti-inflammatory actions of Alafia barteri: involvement of monoaminergic, nitrergic and opioidergic pathway. Nig Q J Hosp Med 2015; 25(2): 118-123.
  40. Erfanparast A, Tamaddonfard A, Henareh-Chareh F. Central histaminergic H2 and alpha2-adrenergic receptor involvement in crocetin-induced antinociception in orofacial formalin pain in rats. Vet Res Forum 2020; 11(3): 229-234.
  41. Parvardeh S, Sabetkasaei M, Moghimi M, et al. Role of L-arginine/NO/cGMP/KATP channel signaling pathway in the central and peripheral antinociceptive effect of thymoquinone in rats. Iran J Basic Med Sci 2018; 21(6): 625-633.
  42. Erfanparast A, Tamaddonfard E, Tamaddonfard S, et al. Opioid and CB1 receptor involvement in central anti-nociceptive effect of vitamin C in the formalin-induced pain model in rats [Persian]. Iran J Physiol Pharmacol 2022; 5(15): 223-232.
  43. Cortright DN, Matson DJ, Broom DC. New frontiers in assessing pain and analgesia in laboratory animals. Expert Opin Drug Discov 2008; 3(9): 1099-1108.
  44. Czigle S, Fialová SB, Tóth J, et al. Treatment of gastrointestinal disorders-plants and potential mechanisms of action of their constituents. Molecules 2022; 27(9): 2881. doi: 10.3390/molecules27092881.
  45. Roudsari NM, Lashgari N-A, Momtaz S, et al. Natural polyphenols for the prevention of irritable bowel syndrome: molecular mechanisms and targets; a comprehensive review. Daru 2019: 27(2): 755-780.
  46. Shakeri F, Gholamnezhad Z, Mégarbane B, et al. Gastrointestinal effects of Nigella sativa and its main constituent, thymoquinone: a review. Avicenna J Phytomed 2016; 6(1): 9-20.
  47. Jarmakiewicz-Czaja S, Zielińska M, Helma K, et al. Effect of Nigella sativa on selected gastrointestinal diseases. Curr Issues Mol Biol 2023; 45(4): 3016-3034.