The Antinociceptive Effect of Adalimumab, a TNF-Alpha Inhibitor, in a Mice Model of Inflammatory Pain

Year 2022, , 89 - 93, 29.09.2022

Mehmet Öz , Hasan Şimşek

https://doi.org/10.46810/tdfd.1150501

Cited By: 2

Abstract

The aim of this study, evaluate the nociceptive effect of adalimumab, a TNF-alpha inhibitor, on formalin-induced inflammatory pain in mice. The antinociceptive activity of adalimumab was determined on adult male BALB-C mice (6 mice in each group) by a formalin-induced inflammatory pain model and hot plate test applied. Diclofenac, which we used as a positive control, showed anti-nociceptive activity in both phases of the formalin test. The effect of the hot plate test at the thirtieth minute was statistically significantly different. Adalimumab was not effective in the neuronal phase of the formalin test but showed an antinociceptive effect in the inflammatory phase. Changes due to adalimumab in the hot plate test did not reach statistical significance. The findings of this study showed that adalimumab, which we applied as a single dose, had antinociceptive activity in the inflammatory phase of the formalin test. This result indicated that the peripheral analgesic effect of adalimumab is stronger.

Keywords

Adalimumab, TNF-alpha, formalin test, inflammatory pain, hot plate test

References

• [1] Wang J. Glial endocannabinoid system in pain modulation. Int J Neurosci 2019;129:94–100. https://doi.org/10.1080/00207454.2018.1503178.
• [2] Wang P, Wen C, Olatunji OJ. Anti-Inflammatory and Antinociceptive Effects of Boesenbergia rotunda Polyphenol Extract in Diabetic Peripheral Neuropathic Rats. J Pain Res 2022;15:779–88. https://doi.org/10.2147/JPR.S359766.
• [3] Jackson T, Thomas S, Stabile V, Han X, Shotwell M, McQueen KAK. Chronic Pain Without Clear Etiology in Low- and Middle-Income Countries: A Narrative Review. Anesth Analg 2016;122:2028–39. https://doi.org/10.1213/ANE.0000000000001287.
• [4] Woolf CJ. What is this thing called pain? J Clin Invest 2010;120:3742–4. https://doi.org/10.1172/JCI45178.
• [5] Sloot S, Boland J, Snowden JA, Ezaydi Y, Foster A, Gethin A, et al. Side effects of analgesia may significantly reduce quality of life in symptomatic multiple myeloma: a cross-sectional prevalence study. Support Care Cancer 2015;23:671–8. https://doi.org/10.1007/s00520-014-2358-1.
• [6] Medzhitov R. Origin and physiological roles of inflammation. Nature 2008;454:428–35. https://doi.org/10.1038/nature07201.
• [7] Horiuchi T, Mitoma H, Harashima S, Tsukamoto H, Shimoda T. Transmembrane TNF-alpha: structure, function and interaction with anti-TNF agents. Rheumatology (Oxford) 2010;49:1215–28. https://doi.org/10.1093/rheumatology/keq031.
• [8] Furst DE, Schiff MH, Fleischmann RM, Strand V, Birbara CA, Compagnone D, et al. Adalimumab, a fully human anti tumor necrosis factor-alpha monoclonal antibody, and concomitant standard antirheumatic therapy for the treatment of rheumatoid arthritis: results of STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis). J Rheumatol 2003;30:2563–71.
• [9] Chang C-W, Wei S-C, Chou J-W, Hsu T-C, Chuang C-H, Lin C-P, et al. Safety and Efficacy of Adalimumab for Patients With Moderate to Severe Crohn’s Disease: The Taiwan Society of Inflammatory Bowel Disease (TSIBD) Study. Intest Res 2014;12:287–92. https://doi.org/10.5217/ir.2014.12.4.287.
• [10] Park J, Lee S-Y, Shon J, Kim K, Lee HJ, Kim KA, et al. Adalimumab improves cognitive impairment, exerts neuroprotective effects and attenuates neuroinflammation in an Aβ1-40-injected mouse model of Alzheimer’s disease. Cytotherapy 2019;21:671–82. https://doi.org/10.1016/j.jcyt.2019.04.054.
• [11] Bahceci İ, Tumkaya L, Mercantepe T, Aslan N, Duran ÖF, Soztanaci US, et al. Inhibition of methotrexate induced toxicity in the adult rat spleen by adalimumab. Drug Chem Toxicol 2022:1–7. https://doi.org/10.1080/01480545.2022.2029880.
• [12] Sarioğlu N, Sunay FB, Yay AH, Korkut O, Erel F, Hişmioğullari AA, et al. Anti-inflammatory effects of adalimumab, tocilizumab, and steroid on lipopolysaccharide-induced lung injury. Turk J Med Sci 2021. https://doi.org/10.3906/sag-2010-303.
• [13] Xu J-J, Guo S, Xue R, Xiao L, Kou J-N, Liu Y-Q, et al. Adalimumab ameliorates memory impairments and neuroinflammation in chronic cerebral hypoperfusion rats. Aging 2021;13:14001–14. https://doi.org/10.18632/aging.203009.
• [14] Correger E, Marcos J, Laguens G, Stringa P, Cardinal-Fernández P, Blanch L. Pretreatment with adalimumab reduces ventilator-induced lung injury in an experimental model. Rev Bras Ter Intensiva 2020;32:58–65. https://doi.org/10.5935/0103-507x.20200010.
• [15] Durmaz S, Kurtoğlu T, Barbarus E, Eliyatkın N, Yılmaz M. TNF-alpha inhibitor adalimumab attenuates endotoxin induced cardiac damage in rats. Acta Cirurgica Brasileira 2020;35:e202000202. https://doi.org/10.1590/s0102-865020200020000002.
• [16] Shuwa HA, Dallatu MK, Yeldu MH, Ahmed HM, Nasir IA. Effects of Adalimumab, an Anti-tumour Necrosis Factor-Alpha (TNF-α) Antibody, on Obese Diabetic Rats. Malays J Med Sci 2018;25:51–62. https://doi.org/10.21315/mjms2018.25.4.5.
• [17] Börcek AÖ, Çivi S, Öcal Ö, Gülbahar Ö. Effects of tumor necrosis factor alpha blocker adalimumab in experimental spinal cord injury. J Korean Neurosurg Soc 2015;57:73–6. https://doi.org/10.3340/jkns.2015.57.2.73.
• [18] Gray MA, Chao C-Y, Staudacher HM, Kolosky NA, Talley NJ, Holtmann G. Anti-TNFα therapy in IBD alters brain activity reflecting visceral sensory function and cognitive-affective biases. PLoS One 2018;13:e0193542. https://doi.org/10.1371/journal.pone.0193542.
• [19] Valle-Dorado MG, Hernández-León A, Nani-Vázquez A, Ángeles-López GE, González-Trujano ME, Ventura-Martínez R. Antinociceptive effect of Mansoa alliacea polar extracts involves opioid receptors and nitric oxide in experimental nociception in mice. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 2022;152:113253. https://doi.org/10.1016/j.biopha.2022.113253.
• [20] Zadeh-Ardabili PM, Rad SK. Anti-pain and anti-inflammation like effects of Neptune krill oil and fish oil against carrageenan induced inflammation in mice models: Current statues and pilot study. Biotechnol Rep (Amst) 2019;22:e00341. https://doi.org/10.1016/j.btre.2019.e00341.
• [21] Damas J, Liégeois JF. The inflammatory reaction induced by formalin in the rat paw. Naunyn Schmiedebergs Arch Pharmacol 1999;359:220–7. https://doi.org/10.1007/pl00005345.
• [22] Yin Z-Y, Li L, Chu S-S, Sun Q, Ma Z-L, Gu X-P. Antinociceptive effects of dehydrocorydaline in mouse models of inflammatory pain involve the opioid receptor and inflammatory cytokines. Sci Rep 2016;6:27129. https://doi.org/10.1038/srep27129.
• [23] Hunskaar S, Hole K. The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain 1987;30:103–14. https://doi.org/10.1016/0304-3959(87)90088-1.
• [24] Torres-Acosta N, O’Keefe JH, O’Keefe EL, Isaacson R, Small G. Therapeutic Potential of TNF-α Inhibition for Alzheimer’s Disease Prevention. J Alzheimers Dis 2020;78:619–26. https://doi.org/10.3233/JAD-200711.
• [25] Tsentemeidou A, Sotiriou E, Sideris N, Kourouklidou A, Lallas A, Ioannides D, et al. Adalimumab Effect on Pain in Hidradenitis Suppurativa Patients: Systematic Review and Meta-Analysis. Dermatol Pract Concept 2022;12:e2022099. https://doi.org/10.5826/dpc.1202a99.
• [26] Jaffal SM, Al-Najjar BO, Abbas MA, Oran SA. Antinociceptive Action of Moringa peregrina is Mediated by an Interaction with α2-Adrenergic Receptor. Balkan Med J 2020;37:189–95. https://doi.org/10.4274/balkanmedj.galenos.2020.2019.11.14.
• [27] Mannan MA, Khatun A, Khan MFH. Antinociceptive effect of methanol extract of Dalbergia sissoo leaves in mice. BMC Complement Altern Med 2017;17:72. https://doi.org/10.1186/s12906-017-1565-y.