Relationship of Anti-interleukin-6 Receptor Antibody to Interleukin-6 Level and Inducible Nitrite Oxide Levels in Peripheral Nerve Injury in Chronic Constriction Injury-Induced Rats: A Case-Control Study in Indonesia

Riki Sukiandra; Eti Yerizel; Yuliarni Syafrita; Eryati Darwin

doi:10.3889/oamjms.2022.7604

Authors

Riki Sukiandra Doctoral Student, Postgraduate Biomedical Science Program, Faculty of Medicine, Universitas Andalas, Padang, Indonesia
Eti Yerizel Department of Biochemistry, Faculty of Medicine, Universitas Andalas, Padang, Indonesia
Yuliarni Syafrita Department of Neurology, Faculty of Medicine, Universitas Andalas, Padang, Indonesia
Eryati Darwin Department of Histology, Faculty of Medicine, Universitas Andalas, Padang, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2022.7604

Keywords:

Neuropathic pain, Peripheral nerve injury, Interleukin-6, Inducible nitric oxide

Abstract

BACKGROUND: Interleukin-6 (IL-6) and inducible Nitric oxide Synthase (iNOS) have an effect on neuropathic pain in the inflammatory process in peripheral nerve injuries.

AIM: This study aims to examine the effect of anti-IL-6 receptor antibody on IL-6 and iNOS levels as a consideration for the treatment of neuropathic pain in a rat model of peripheral nerve injury.

METHODS: Twenty-eight young adult male Wistar rats were treated for peripheral nerve injury and then divided into two groups. Fourteen treatment groups (Group P) were given anti-IL-6 receptor antibody by injection at a dose of 100 g/day by injection into the saphenous vein in the rat’s leg for 3 days. In both groups, the serum IL-6 and iNOS levels were assessed on the 3^rdday after administration of anti-IL-6 receptor antibody in group P, using the sandwich ELISA method.

RESULTS: The results showed that the administration of anti-IL-6 receptor antibody did not have a significant effect on reducing IL-6 and iNOS levels in group P (p > 0.05). Administration of anti-IL-6 receptor antibody had more effect on IL-6 levels on iNOS levels, where a decrease in IL-6 levels caused a decrease in iNOS levels in group P (p = 0.004 and r = 0.693).

CONCLUSIONS: We conclude that the present administration of anti-IL-6 receptor antibody cannot be considered as a treatment for neuropathic pain in peripheral nerve injuries, but can be used to influence IL-6 levels on iNOS levels.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Nicholson B. Differential diagnosis: Nociceptive and neuropathic pain. Am J Manag Care. 2006;12 Suppl 9:S256-62. PMid:16774457

Borda AP, Sonnek FC, Fonteyne V, Papaioannou EG. Guidelines on Pain Management and Palliative Care. Arnhem, Netherlands: European Association of Urology; 2013. p. 70.

Akkurt HE, Gümüs H, Göksu H, Odaba OF, Yilmaz H. Gabapentin treatment for neuropathic pain in a child with sciatic nerve injury. Case Rep Med. 2015;2015:873157. DOI: https://doi.org/10.1155/2015/873157

McMahon SB, Malcangio M. Current challenges in glia-pain biology. Neuron. 2009;64(1):46-54. https://doi.org/10.1016/j.neuron.2009.09.033 PMid:19840548 DOI: https://doi.org/10.1016/j.neuron.2009.09.033

McCarberg BH, Billington R. Consequences of neuropathic pain: Quality-of-life issues and associated costs. Am J Manag Care. 2006;12 Suppl 9:S263-8. PMid:16774458

Childers WE Jr., Baudy RB. N-methyl-D-aspartate antagonists and neuropathic pain: The search for relief. J Med Chem. 2007;50(11):2557-62. https://doi.org/10.10a/jm060728b PMid:17489572 DOI: https://doi.org/10.1021/jm060728b

Inoue K, Tsuda M. Microglia and neuropathic pain. Glia. 2009;57(14):1469-79. https://doi.org/10.1002/glia.20871 PMid:19306358 DOI: https://doi.org/10.1002/glia.20871

Milligan ED, Watkins LR. Pathological and protective roles of glia in chronic pain. Nat Rev Neurosci. 2009;10(1):23-36. https://doi.org/10.1038/nrn2533 PMid:19096368 DOI: https://doi.org/10.1038/nrn2533

Zhuo M. A synaptic model for pain: Long-term potentiation in the anterior cingulate cortex. Mol Cells. 2007;23(3):259-71. PMid:17646700

Kandel ER. The molecular biology of memory storage: A dialogue between genes and synapses. Science. 2001;294(5544):1030-8. https://doi.org/10.1126/science.1067020 PMid:11691980 DOI: https://doi.org/10.1126/science.1067020

Vallance P, Leiper J. Blocking no synthesis: How, where and why? Nat Rev Drug Discov. 2002;1(12):939-50. https://doi.org/10.1038/nrd960 PMid:12461516 DOI: https://doi.org/10.1038/nrd960

Zhang W, Liu LY, Xu TL. Reduced potassium-chloride co-transporter expression in spinal cord dorsal horn neurons contributes to inflammatory pain hypersensitivity in rats. Neuroscience. 2008;152(2):502-10. https://doi.org/10.1016/j.neuroscience.2007.12.037 PMid:18262726 DOI: https://doi.org/10.1016/j.neuroscience.2007.12.037

Li P, Wilding TJ, Kim SJ, Calejesan AA, Huettner JE, Zhuo M. Kainate-receptor-mediated sensory synaptic transmission in mammalian spinal cord. Nature. 1999;397(6715):161-4. https://doi.org/10.1038/16469 PMid:9923678 DOI: https://doi.org/10.1038/16469

Wu LJ, Zhuo M. Targeting the NMDA receptor subunit NR2B for the treatment of neuropathic pain. Neurotherapeutics. 2009;6(4):693-702. https://doi.org/10.1016/j.nurt.2009.07.008 PMid:19789073 DOI: https://doi.org/10.1016/j.nurt.2009.07.008

Ji RR, Kohno T, Moore KA, Woolf CJ. Central sensitization and LTP: Do pain and memory share similar mechanisms? Trends Neurosci. 2003;26(12):696-705. https://doi.org/10.1016/j.tins.2003.09.017 PMid:14624855 DOI: https://doi.org/10.1016/j.tins.2003.09.017

Ikeda H, Heinke B, Ruscheweyh R, Sandkuhler J. Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia. Science. 2003;299(5610):1237-40. https://doi.org/10.1126/science.1080659 PMid:12595694 DOI: https://doi.org/10.1126/science.1080659

Sandkuhler J. Understanding LTP in pain pathways. Mol Pain. 2007;3:9. https://doi.org/10.1186/1744-8069-3-9. PMid:17407590 DOI: https://doi.org/10.1186/1744-8069-3-9

Murakami A, Kanchiku T. Anti-interleukin-6 receptor antibody reduces neuropathic pain following spinal cord injury in mice. Exp Ther Med. 2013;6(5):1194-8. https://doi.org/10.3892/etm.2013.1296 PMid:24223643 DOI: https://doi.org/10.3892/etm.2013.1296

Kolios G, Brown Z, Robson RL, Robertson DA, Westwick J. Inducible nitric oxide synthase activity and expression in a human colonic epithelial cell line, HT-29. Br J Pharmacol. 1995;116(7):2866-72. https://doi.org/10.1111/j.1476-5381.1995.tb15938.x PMid:8680718 DOI: https://doi.org/10.1111/j.1476-5381.1995.tb15938.x

Amin B, Hosseinzadeh H. Evaluation of aqueous and ethanolic extracts of saffron, Crocus sativus L., and its constituents, safranal and crocin in allodynia and hyperalgesia induced by chronic constriction injury model of neuropathic pain in rats. Fitoterapia. 2012;83(5):888-95. https://doi.org/10.1016/j.fitote.2012.03.022 PMid:22484092 DOI: https://doi.org/10.1016/j.fitote.2012.03.022

Bhardwaj HC, Muthuraman A, Hari KS, Navis S. Antioxidative and anti-inflammatory potentials of ambroxol in ameliorating vincristine induced peripheral neuropathic pain in rats. J Neuroinfect Dis. 2016;7:202.

Fregnan F, Muratori L, Simões AR, Giacobini-Robecchi MG, Raimondo S. Role of inflammatory cytokines in peripheral nerve injury. Neural Regen Res. 2012;7(29):2259-66. https://doi.org/10.3969/j.issn.1673-5374.2012.29.003 PMid:25538747