Melatonin and the intervertebral disc: a potential intervention for lower back pain?
Melatonin and the intervertebral disc
Keywords:
Melatonon, Intervertebral disc, reactive oxygen species, senescence, inflammation
Abstract
Lower back pain is a common disability associated with aging that continues to carry a huge economic and health burden globally. Importantly, lower back pain is strongly associated with diseases involving intervertebral discs (IVDs), and many of the treatment options for the repair and maintenance of the IVDs are insufficient. Being a well-tolerated and endogenously produced molecule, melatonin is a suitable candidate for the treatment and prevention of a wide variety of skeletal conditions. In this review, we have evaluated current updates regarding melatonin’s activities in IVD degenerative disease and discuss multiple mechanisms related to its effects on inflammation, oxidative stress, autophagy and senescence that contribute towards its support of the IVDs as well as its benefits in the treatment of IVD disease.
References
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2. Chen S, et al. (2021) Global, regional and national burden of low back pain 1990–2019: A systematic analysis of the Global Burden of Disease study 2019. J. Orthop. Translat. 32: 49-58.
3. Dieleman JL, et al. (2020) US health care spending by payer and health condition, 1996-2016. JAMA 323: 863.
4. Dutmer AL, et al. (2019) Personal and societal impact of low back pain: The groningen spine cohort. Spine 44: E1443.
5. Brinjikji W, et al. (2015) MRI findings of disc degeneration are more prevalent in adults with low back pain than in asymptomatic controls: A systematic review and meta-analysis. AJNR Am. J. Neuroradiol. 36: 2394-2399.
6. Mohd IIL, et al. (2023) Discogenic low back pain: anatomy, pathophysiology and treatments of intervertebral disc degeneration. Int. J. of Mol. Sci. 24: 208.
7. Lu X, et al. (2021) Insight into the roles of melatonin in bone tissue and bone‑related diseases (Review). Int. J. Mol. Med. 47: 82.
8. Reiter RJ, et al. (2019) Melatonin: Protection of the Intervertebral Disc. Melatonin Res. 2: 1-9.
9. Xie W, et al. (2021) Melatonin: Effects on cartilage homeostasis and therapeutic prospects in cartilage-related diseases. Aging Dis. 12: 297-307.
10. Alonso F, et al. (2014) "Intervertebral Disk" in Encyclopedia of the Neurological Sciences (Second Edition), Aminoff MJ, Daroff RB, Eds. (Academic Press, Oxford, 2014), https://doi.org/10.1016/B978-0-12-385157-4.01154-4, pp. 724-729.
11. Sharabi M (2022) Structural mechanisms in soft fibrous tissues: A review. Front. Materi. 8: 1-28.
12. Clouet J, et al. (2009) The intervertebral disc: From pathophysiology to tissue engineering. Joint, bone, spine 76: 614-618.
13. Singh K, et al. (2009) Age-related changes in the extracellular matrix of nucleus pulposus and anulus fibrosus of human intervertebral disc. Spine (Phila Pa 1976) 34: 10-16.
14. Iatridis JC, et al. (2005) Mechanical damage to the intervertebral disc annulus fibrosus subjected to tensile loading. J. Biomech. 38: 557-565.
15. Urban JPG, et al. (2003) Degeneration of the intervertebral disc. Arthritis Res. Ther. 5: 120.
16. Fields AJ, et al. (2018) Contribution of the endplates to disc degeneration. Cur.Mol. Biol. Rep: 4: 151-160.
17. Nerlich AG, et al. (2007) Temporo-spatial distribution of blood vessels in human lumbar intervertebral discs. Eur. Spine J. 16: 547-555.
18. Bernick S, et al. (1982) Vertebral end-plate changes with aging of human vertebrae. Spine 7: 97-102.
19. Dudek M, et al. (2017) The intervertebral disc contains intrinsic circadian clocks that are regulated by age and cytokines and linked to degeneration. Ann. Rheum. Dis. 76: 576-584.
20. Newell N, et al. (2017) Biomechanics of the human intervertebral disc: A review of testing techniques and results. J. Mech. Behav. Biomed. Mater. 69: 420-434.
21. Zhang T, et al. (2020) The circadian rhythm in intervertebral disc degeneration: an autophagy connection. Exp. Mol. Med. 52: 31-40.
22. Turgut M, et al. (2006) Surgical pinealectomy accelerates intervertebral disc degeneration process in chicken. Eur. Spine J. 15: 605-612.
23. Bian Q, et al. (2017) Mechanosignaling activation of TGFβ maintains intervertebral disc homeostasis. Bone Res. 5: 17008.
24. Latorre A, et al. (1998) Experimental model of multidirectional disc hernia in rats. Int. Orthop. 22: 44-48.
25. Turgut M, et al. (2006) The effect of exogenous melatonin administration on trabecular width, ligament thickness and TGF-β1 expression in degenerated intervertebral disk tissue in the rat. J. Clin. Neurosci. 13: 357-363.
26. Shen C, et al. (2020) Melatonin prevents the binding of vascular endothelial growth factor to its receptor and promotes the expression of extracellular matrix-associated genes in nucleus pulposus cells. Exp. Ther. Med. 20: 106.
27. Oh C, et al. (2016) SOX9 directly Regulates CTGF/CCN2 transcription in growth plate chondrocytes and in nucleus pulposus cells of intervertebral disc. Sci. Rep. 6: 29916.
28. Wang S. et al. (2013) Effects of TGF-β1 and IL-1β on expression of ADAMTS enzymes and TIMP-3 in human intervertebral disc degeneration. Exp. Ther. Med. 6: 1522-1526.
29. Yang H, et al. (2015) TGF-βl suppresses inflammation in cell therapy for intervertebral disc degeneration. Sci. Rep. 5: 13254.
30. Yang H, et al. (2015) TGF- β 1 antagonizes TNF- α induced up-regulation of matrix metalloproteinase 3 in nucleus pulposus cells: role of the ERK1/2 pathway. Connect. Tissue Res. 56: 461-468.
31. Ge J, et al. (2019) Melatonin protects intervertebral disc from degeneration by improving cell survival and function via activation of the ERK1/2 signaling pathway. Oxid. Med. Cell. Longev. 2019: 5120275.
32. Dou X, et al. (2023) Therapeutic potential of melatonin in the intervertebral disc degeneration through inhibiting the ferroptosis of nucleus pulpous cells. J. Cell. Mol. Med. 27: 2340-2353.
33. Feng C, et al. (2016) Disc cell senescence in intervertebral disc degeneration: Causes and molecular pathways. Cell Cycle 15: 1674-1684.
34. Roberts S, et al. (2006) Histology and pathology of the human intervertebral disc. J. Bone Joint Surg. Am. 88 Suppl 2: 10-14.
35. Li Z. et al. (2017) Melatonin inhibits nucleus pulposus (NP) cell proliferation and extracellular matrix (ECM) remodeling via the melatonin membrane receptors mediated PI3K-Akt pathway. J. Pineal Res. 63: e12435.
36. Qiu X. et al. (2022) Melatonin reverses tumor necrosis factor-alpha-induced metabolic disturbance of human nucleus pulposus cells via MTNR1B/Gαi2/YAP signaling. Int. J. Biol. Sci. 18: 2202-2219.
37. Zhao B, et al. (2010) A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCFβ-TRCP. Genes Dev. 24: 72-85.
38. Chen F, et al. (2020) Melatonin activates autophagy via the NF-κB signaling pathway to prevent extracellular matrix degeneration in intervertebral disc. Osteoarthritis Cartilage 28: 1121-1132.
39. Oktem G, et al. (2006) Evaluation of the relationship between inducible nitric oxide synthase (iNOS) activity and effects of melatonin in experimental osteoporosis in the rat. Surg. Radiol. Anat. 28: 157-162.
40. Simon PS, et al. (2015) The NF-κB p65 and p50 homodimer cooperate with IRF8 to activate iNOS transcription. BMC Cancer 15: 770.
41. Ma H, et al. (2021) ROR: Nuclear receptor for melatonin or not? Molecules 26 (9): 2693.
42. Liang T, et al. (2021) Inverse agonist of retinoid-related orphan receptor-alpha prevents apoptosis and degeneration in nucleus pulposus cells via upregulation of YAP. Mediators Inflamm. 2021: 9954909.
43. Wang Y, et al. (2020) The role of IL-1β and TNF-α in intervertebral disc degeneration. Biomed. Pharmacother. 131: 110660.
44. Zhang Y, et al. (2019) Melatonin modulates IL-1β-induced extracellular matrix remodeling in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration and inflammation. Aging 11: 10499-10512.
45. Chen F, et al. (2020) Melatonin alleviates intervertebral disc degeneration by disrupting the IL-1β/NF-κB-NLRP3 inflammasome positive feedback loop. Bone Res. 8: 10.
46. Le MCL, et al. (2005) The role of interleukin-1 in the pathogenesis of human intervertebral disc degeneration. Arthritis Res. Ther. 7: R732.
47. Huang Y, et al. (2020) Nicotinamide phosphoribosyl transferase controls NLRP3 inflammasome activity through MAPK and NF-κB signaling in nucleus pulposus cells, as suppressed by melatonin. Inflammation 43: 796-809.
48. Shi C, et al. (2018) Nicotinamide phosphoribosyltransferase inhibitor APO866 prevents IL-1β-induced human nucleus pulposus cell degeneration via autophagy. Cell. Physiol. Biochem. 49: 2463-2482.
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Published
2024-04-30
How to Cite
[1]
File, C. and Sharma, R. 2024. Melatonin and the intervertebral disc: a potential intervention for lower back pain?. Melatonin Research. 7, 1 (Apr. 2024), 84-102. DOI:https://doi.org/https://doi.org/10.32794/mr112500169.
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