Veterinary Research Forum
Vet Res Forum

Thymoquinone attenuates paw incision-induced spontaneous and evoked pain through anti-oxidative and anti-inflammatory mechanisms in rats

Document Type : Original Article

Authors

Seyed Siavash Ghoreishi 1
Saeed Azizi 2
Esmaeal Tamaddonfard 3
Safiyeh Aghazadeh 3

1 DVSc Candidate, Department of Surgery and Diagnostic Imaging, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

2 Department of Surgery and Diagnostic Imaging, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

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

https://doi.org/10.30466/vrf.2024.2025053.4204
Abstract
Surgery commonly causes post-operative pain that should be alleviated to prevent complications. In addition to the use of synthetic drugs, there has been a widespread desire to use medicinal plants for surgical pain management. Thymoquinone (TQ), a constituent of Nigella sativa black seeds, exhibits a potent anti-oxidant property. Celecoxib (CLX), a potent non-steroidal anti-inflammatory drug, is widely used in pain management. In the present study, the effects of TQ and CLX on pain caused by hind paw surgical incision were compared. Fifty-six rats were divided into four groups of 14 rats as intact, vehicle, TQ, and CLX groups. In each group, six rats were planned to record pain-related behaviors on days 1 - 10 and eight rats were designed for determination of serum biochemical alterations on days 1 (four rats) and 3 (four rats) after surgery. Oral administrations of TQ and CLX at a same dose of 10.00 mg kg-1 alleviated paw lifting number (spontaneous pain) and paw withdrawal threshold evoked by von Frey filaments on metal mesh floor, improved the decreased contents of serum total anti-oxidant capacity and superoxide dismutase, and restored the increased levels of serum malondialdehyde and tumor necrosis factor-alpha. The results suggested that TQ by employing anti-oxidant and anti-inflammatory mechanisms, might relieve the pain induced by hind paw plantar incision, being comparable with CLX.

Keywords

Celecoxib
Incision
Pain
Rats
Thymoquinone

Subjects

  1. Ghoneim MM, O'Hara MW. Depression and post-operative complications: an overview. BMC Surg 2016; 16: 5. doi: 10.1186/s12893-016-0120-y.
  2. Chapman CR, Vierck CJ. The transition of acute postoperative pain to chronic pain: an integrative overview of research on mechanisms. J Pain 2017; 18(4):359.e1-359.e38. doi: 10.1016/j.jpain.2016.11.004.
  3. Small C, Laycock H. Acute postoperative pain management. Br J Surg 2020; 107(2): e70-e80. doi: 10.1002/bjs.11477.
  4. Harirforoosh S, Asghar W, Jamali F. Adverse effects of nonsteroidal antiinflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications J Pharm Pharm Sci 2013; 16(5): 821-847.
  5. Benyamin R, Trescot AM, Datta S, et al. Opioid complications and side effects. Pain Physician 2008; 11(2 Suppl): S105-S120.
  6. Mitra S, Carlyle D, Kodumudi G, et al. New advances in acute postoperative pain management. Curr Pain Headache Rep 2018; 22(5): 35. doi: 10.1007/s11916-018-0690-8.
  7. Park KM, Kim JH. Herbal medicine for the management of postoperative pain: a protocol for the systematic review of randomized controlled trials. Medicine (Baltimore). 2019; 98(1): e14016. doi: 10.1097/MD.0000000000014016.
  8. Arruda APN, Ayala AP, Lopes LC, et al. Herbal medications for surgical patients: a systematic review protocol. BMJ Open 2017; 7(7): e014290. doi: 10.1136/bmjopen-2016-014290.
  9. Biddlestone L, Corbett AD, Dolan S. Oral administration of Ginkgo biloba extract, EGb-761 inhibits thermal hyperalgesia in rodent models of inflammatory and post-surgical pain. Br J Pharmacol 2007; 151(2):
    285-291.
  10. Hannan MA, Rahman MA, Sohag AAM, et al. Black cumin (Nigella sativa ): a comprehensive review on phytochemistry, health benefits, molecular pharmacology, and safety. Nutrients 2021; 13(6): 1784. doi: 10.3390/nu13061784.
  11. Pottoo FH, Ibrahim AM, Alammar A, et al. Thymoquinone: review of its potential in the treatment of neurological diseases. Pharmaceuticals (Basel) 2022; 15(4): 408. doi: 10.3390/ph15040408.
  12. 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.
  13. Amin B, Taheri MM, Hosseinzadeh H. Effects of intraperitoneal thymoquinone on chronic neuropathic pain in rats. Planta Med 2014; 80(15): 1269-1277.
  14. Pogatzki-Zahn EM, Segelcke D, Schug SA. Postoperative pain-from mechanisms to treatment. Pain Rep 2017; 2(2): e588. doi: 10.1097/PR9.0000000000000588.
  15. Gupta A, Bah M. NSAIDs in the treatment of postoperative pain. Curr Pain Headache Rep 2016; 20(11): 62. doi: 10.1007/s11916-016-0591-7.
  16. Whiteside GT, Harrison J, Boulet J, et al. Pharmacological characterization of a rat model of incisional pain. Br J Pharmacol 2004; 141(1): 85-91.
  17. Brennan TJ, Vandermeulen EP, Gebhart GF. Characterization of a rat model of incisional pain. Pain 1996; 64(3): 493-502. 
  18. Naderi S, Tamaddonfard E, Nafisi S, et al. Effect of thymoquinone on acetic acid-induced visceral nociception in rats: role of central cannabinoid and α2-adrenergic receptors. Vet Res Forum 2024; 15(3): 131-138.
  19. Craft RM, Hewitt KA, Britch SC. Antinociception produced by nonsteroidal anti-inflammatory drugs in female vs male rats. Behav Pharmacol 2021; 32(2&3): 153-169.
  20. Kumar R, Gupta S, Gautam M, et al. Diverse characters of Brennan's paw incision model regarding certain parameters in the rat. Korean J Pain 2019; 32(3): 168-177.
  21. Kabadi R, Kouya F, Cohen HW, et al. Spontaneous pain-like behaviors are more sensitive to morphine and buprenorphine than mechanically evoked behaviors in a rat model of acute postoperative pain. Anesth Analg 2015; 120(2): 472-478.
  22. Ying YL, Wei XH, Xu XB, et al. Over-expression of P2X7 receptors in spinal glial cells contributes to the development of chronic postsurgical pain induced by skin/muscle incision and retraction (SMIR) in rats. Exp Neurol 2014; 261: 836-843.
  23. Chen H, Jiang YS, Sun Y, et al. p38 and interleukin-1 beta pathway via toll-like receptor 4 contributed to the skin and muscle incision and retraction-induced allodynia. J Surg Res 2015; 197(2): 339-347.
  24. Wang Y, Liu Y, Liu J, et al. Coadministration of curcumin and hydromorphone hydrochloride alleviates postoperative pain in rats. Biol Pharm Bull 2022; 45(1): 27-33.
  25. Joksimovic SL, Lamborn N, Jevtovic-Todorovic V, et al. Alpha lipoic acid attenuates evoked and spontaneous pain following surgical skin incision in rats. Channels (Austin) 2021; 15(1): 398-407.
  26. Hämäläinen MM, Gebhart GF, Brennan TJ. Acute effect of an incision on mechanosensitive afferents in the plantar rat hind paw. J Neurophysiol 2002; 87(2): 712-720.
  27. Pogatzki EM, Gebhart GF, Brennan TJ. Characterization of Adelta- and C-fibers innervating the plantar rat hind paw one day after an incision. J Neurophysiol 2002; 87(2): 721-731.
  28. Silvestrini A, Meucci E, Ricerca BM, et al. Total antioxidant capacity: biochemical aspects and clinical significance. Int J Mol Sci 2023; 24(13): 10978. doi: 10.3390/ijms241310978.
  29. Ayala A, Muñoz MF, Argüelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev 2014; 2014: 360438. doi: 10.1155/ 2014/360438.
  30. Varfolomeev E, Vucic D. Intracellular regulation of TNF activity in health and disease. Cytokine 2018; 101:
    26-32.
  31. Bedir Z, Ozkaloglu Erdem KT, Doymus O, et al. Effects of benidipine, paracetamol, and their combination on postoperative and normal tissue pain thresholds. Front Pharmacol 2024; 14: 1326128. doi: 10.3389/fphar. 2023.1326128.
  32. Lv CC, Xia ML, Shu SJ, et al. Attenuation of remifentanil-induced hyperalgesia by betulinic acid associates with inhibiting oxidative stress and inflammation in spinal dorsal horn. Pharmacology 2018; 102(5-6): 300-306.
  33. Loram LC, Themistocleous AC, Fick LG, et al. The time course of inflammatory cytokine secretion in a rat model of postoperative pain does not coincide with the onset of mechanical hyperalgesia. Can J Physiol Pharmacol 2007; 85(6): 613-620.
  34. Finnerty CC, Mabvuure NT, Ali A, et al. The surgically induced stress response. JPEN J Parenter Enteral Nutr 2013; 37(5 Suppl): 21S-29S.
  35. Celik F, Göçmez C, Karaman H, et al. Therapeutic effects of thymoquinone in a model of neuropathic pain. Curr Ther Res Clin Exp 2014; 76: 11-16.
  36. Chang RW, Tompkins DM, Cohn SM. Are NSAIDs safe? Assessing the risk-benefit profile of nonsteroidal anti-inflammatory drug use in postoperative pain management. Am Surg 2021; 87(6): 872-879.
  37. Moore RA, Derry S, McQuay HJ, et al. Single dose oral analgesics for acute postoperative pain in adults. Cochrane Database Syst Rev 2011; 9: CD008659. doi: 10.1002/14651858.CD008659.pub2.
  38. Merlos M, Portillo-Salido E, Brenchat A, et al. Administration of a co-crystal of tramadol and celecoxib in a 1:1 molecular ratio produces synergistic antinociceptive effects in a postoperative pain model in rats. Eur J Pharmacol 2018; 833: 370-378.
  39. Abd-Elmawla MA, Abdelalim E, Ahmed KA, et al. The neuroprotective effect of pterostilbene on oxaliplatin-induced peripheral neuropathy via its anti-inflammatory, anti-oxidative and anti-apoptotic effects: comparative study with celecoxib. Life Sci 2023; 315: 121364. doi: 10.1016/j.lfs.2022.121364.
  40. Hanzawa A, Handa T, Kohkita Y, et al. A comparative study of oral analgesics for postoperative pain after minor oral surgery Anesth Prog 2018; 65(1): 24-29.
  41. Vieira SF, Ferreira H, Neves NM. Antioxidant and anti-Inflammatory activities of cytocompatible Salvia officinalis extracts: a comparison between traditional and soxhlet extraction. Antioxidants (Basel) 2020; 9(11): 1157. doi: 10.3390/antiox9111157.
Veterinary Research Forum
Volume 16, Issue 2
February 2025
Pages 89-96

  • Receive Date 16 March 2024
  • Revise Date 17 April 2024
  • Accept Date 07 May 2024

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