IL-10 Stimulates Microglia and Neurons to Produce Endogenous Opioid Peptides and Reduce Neuro-Inflammatory Chronic Pain
Journal: Journal of Clinical Medicine Research DOI: 10.32629/jcmr.v5i3.2769
Abstract
Chronic pain, persisting beyond three months, affects millions worldwide with no effective treatments. While some anti-inflammatory cytokines like IL-4 can trigger macrophages to produce pain-relieving opioid peptides, the role of IL-10 in this process remains unexplored. This study investigates IL-10's potential to stimulate opioid peptide production in neurons and glial cells and reduce pain. Using immunofluorescent staining, enzyme immunoassays, and the Von Frey test, we examined cells treated with LPS and cytokines, and assessed pain reduction in mouse models. Our findings suggest that IL-10 can trigger neurons and microglia to produce opioid peptides, albeit less efficiently than IL-4. These results indicate a potential new target for chronic pain treatment, combining IL-4 and IL-10 therapies, offering a promising alternative to current pain management strategies.
Keywords
microglia, neuroinflammation, anti-inflammation, cytokine, endogenous opioid peptide, IL-4, IL-10
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[2]Busch-Dienstfertig, M., & González-Rodríguez, S. (2013). IL-4, JAK-STAT signaling, and pain. Jak-stat, 2(4), e27638.
[3]Celik, M. Ö., Labuz, D., Keye, J., Glauben, R., & Machelska, H. (2020). IL-4 induces M2 macrophages to produce sustained analgesia via opioids. JCI Insight, 5(4). https://doi.org/10.1172/jci.insight.133093
[4]Chau, D. L., Walker, V., Pai, L., & Cho, L. M. (2008). Opiates and elderly: use and side effects. Clinical interventions in aging, 3(2), 273-278.
[5]Chou, R., Hartung, D., Turner, J., Blazina, I., Chan, B., Levander, X., McDonagh, M., Selph, S., Fu, R., & Pappas, M. (2020). Opioid treatments for chronic pain.
[6]Dubbelaar, M. L., Kracht, L., Eggen, B. J. L., & Boddeke, E. W. G. M. (2018). The Kaleidoscope of Microglial Phenotypes [Review]. Frontiers in Immunology, 9. https://doi.org/10.3389/fimmu.2018.01753
[7]Eggen, B. J., Raj, D., Hanisch, U.-K., & Boddeke, H. W. (2013). Microglial phenotype and adaptation. Journal of Neuroimmune Pharmacology, 8, 807-823.
[8]Fenn, A. M., Henry, C. J., Huang, Y., Dugan, A., & Godbout, J. P. (2012). Lipopolysaccharide-induced interleukin (IL)-4 receptor-α expression and corresponding sensitivity to the M2 promoting effects of IL-4 are impaired in microglia of aged mice. Brain, Behavior, and Immunity, 26(5), 766-777. https://doi.org/https://doi.org/10.1016/j.bbi.2011.10.003
[9]Glajchen, M. (2001). Chronic pain: treatment barriers and strategies for clinical practice. The Journal of the American Board of Family Practice, 14(3), 211-218.
[10]Holden, J. E., Jeong, Y., & Forrest, J. M. (2005). The Endogenous Opioid System and Clinical Pain Management. AACN Advanced Critical Care, 16(3), 291-301.
[11]Hylands-White, N., Duarte, R. V., & Raphael, J. H. (2017). An overview of treatment approaches for chronic pain management. Rheumatology International, 37(1), 29-42. https://doi.org/10.1007/s00296-016-3481-8
[12]Ip, W. E., Hoshi, N., Shouval, D. S., Snapper, S., & Medzhitov, R. (2017). Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages. Science, 356(6337), 513-519.
[13]Ji, R.-R., Xu, Z.-Z., & Gao, Y.-J. (2014). Emerging targets in neuroinflammation-driven chronic pain. Nature reviews Drug discovery, 13(7), 533-548.
[14]Jr, R. S. S. A. S. K. G. G. (2019-2021). Chronic Pain Among Adults — United States. MMWR Morb Mortal Wkly Rep 2023, 72, 379–385. https://doi.org/http://dx.doi.org/10.15585/mmwr.mm7215a1
[15]Jurga, A. M., Paleczna, M., & Kuter, K. Z. (2020). Overview of general and discriminating markers of differential microglia phenotypes. Frontiers in cellular neuroscience, 14, 198.
[16]Lively, S., & Schlichter, L. C. (2018). Microglia Responses to Pro-inflammatory Stimuli (LPS, IFNγ+TNFα) and Reprogramming by Resolving Cytokines (IL-4, IL-10) [Original Research]. Frontiers in cellular neuroscience, 12. https://doi.org/10.3389/fncel.2018.00215
[17]Ouyang, W., Rutz, S., Crellin, N. K., Valdez, P. A., & Hymowitz, S. G. (2011). Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annual review of immunology, 29, 71-109.
[18]Pasternak, G. W. (1993). Pharmacological mechanisms of opioid analgesics. Clinical neuropharmacology, 16(1), 1-18.
[19]Sanjabi, S., Zenewicz, L. A., Kamanaka, M., & Flavell, R. A. (2009). Anti-inflammatory and pro-inflammatory roles of TGF-β, IL-10, and IL-22 in immunity and autoimmunity. Current opinion in pharmacology, 9(4), 447-453.
[20]Shabab, T., Khanabdali, R., Moghadamtousi, S. Z., Kadir, H. A., & Mohan, G. (2017). Neuroinflammation pathways: a general review. International Journal of Neuroscience, 127(7), 624-633. https://doi.org/10.1080/00207454.2016.1212854
[21]Smith, B. H., Elliott, A. M., Chambers, W. A., Smith, W. C., Hannaford, P. C., & Penny, K. (2001). The impact of chronic pain in the community. Family Practice, 18(3), 292-299. https://doi.org/10.1093/fampra/18.3.292
[22]Ventafridda, V., Saita, L., Ripamonti, C., & De Conno, F. (1985). WHO guidelines for the use of analgesics in cancer pain. International journal of tissue reactions, 7(1), 93-96. http://europepmc.org/abstract/MED/2409039
[23]Vergne-Salle, P., & Bertin, P. (2021). Chronic pain and neuroinflammation. Joint Bone Spine, 88(6), 105222. https://doi.org/https://doi.org/10.1016/j.jbspin.2021.105222
[24]Wang, X.-s., Guan, S.-y., Liu, A., Yue, J., Hu, L.-n., Zhang, K., Yang, L.-k., Lu, L., Tian, Z., Zhao, M.-g., & Liu, S.-b. (2019). Anxiolytic effects of Formononetin in an inflammatory pain mouse model. Molecular Brain, 12(1), 36. https://doi.org/10.1186/s13041-019-0453-4
[25]Yanik, B. M., Dauch, J. R., & Cheng, H. T. (2020). Interleukin-10 Reduces Neurogenic Inflammation and Pain Behavior in a Mouse Model of Type 2 Diabetes. J Pain Res, 13, 3499-3512. https://doi.org/10.2147/jpr.S264136
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