Chronic pain is a multifaceteddebilitating experience
often associated with significant physical and emotional burden. Low dose
naltrexone (LDN) has gained attention in recent years for its potential utility
in the management of fibromyalgia, irritable
bowel syndrome, multiple sclerosis, and painful diabetic neuropathy. LDN’s analgesic effects have been
associated with its ability to increase the production of endorphins
while reducing the production of tumor
necrosis factor-alpha, interleukin-6, reactive oxygen species and nitric
oxide. This meta-analysis aims to
systematically review and synthesize the available evidence on efficacy
of LDN as an analgesic in pain syndromes, with a focus on chronic (neuro)
inflammatory diseases. The goal is to provide clinicians with a more
comprehensive estimate of the effectiveness of LDN as a non-opioid option for
managing chronic pain and guide future research in the area. Thirteen randomized control trials, published from 1990 to 2022,
were selected for the analysis that satisfied inclusion criteria. The overall effects
in these studies were calculated using the standardized mean difference (SMD)
between the LDN and placebo groups. We found an overall SMD of -10.77 (95% CI:-13.96 to -7.58)
with a p-value of 0.002. This indicated that the LDN group experienced a
statistically significant reduction in pain
compared to placebo. This meta-analysis provides evidence for the potential
efficacy of low dose naltrexone in reducing pain and enhancing analgesia in
various pain syndromes. LDN may be a useful treatment option for patients
suffering from chronic pain, particularly with fibromyalgia, multiple
sclerosis, or diabetic neuropathy. However,
References
[1]
Institute of Medicine (US) Committee on Advancing Pain Research, Care, and Education (2011) Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. National Academies Press, Washington DC.
[2]
Häuser, W., Petzke, F. and Radbruch, L. (2017) The Opioid Epidemic and National Guidelines for Opioid Therapy for Chronic Noncancer Pain: A Perspective from Different Continents. Pain Reports, 2, e599. https://doi.org/10.1097/PR9.0000000000000599
[3]
Toljan, K. and Vrooman, B. (2018) Low-Dose Naltrexone (LDN)—Review of Therapeutic Utilization. Medical Sciences (Basel), 6, Article 82. https://doi.org/10.3390/medsci6040082
[4]
Parkitny, L. and Younger, J. (2015) Reduced Pro-Inflammatory Cytokines after Eight Weeks of Low-Dose Naltrexone for Fibromyalgia. Biomedicines, 3, 294-304.
[5]
Kariv, R., Tiomny, E., Grenshpon, R., Dekel, R., Waisman, G. and Ringel, Y. (2006) Low-Dose Naltrexone for the Treatment of Irritable Bowel Syndrome: A Pilot Randomized, Double-Blind, Placebo-Controlled Trial. Pain Practice, 6, 98-105.
[6]
Younger, J. and Mackey, S. (2009) Fibromyalgia Symptoms Are Reduced by Low-Dose Naltrexone: A Pilot Study. Pain Medicine, 10, 663-672. https://doi.org/10.1111/j.1526-4637.2009.00613.x
[7]
Younger, J., Parkitny, L. and McLain, D. (2014) The Use of Low-Dose Naltrexone (LDN) as a Novel Anti-Inflammatory Treatment for Chronic Pain. Clinical Rheumatology, 33, 451-459. https://doi.org/10.1007/s10067-014-2517-2
[8]
(2012) LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda MD. https://www.ncbi.nlm.nih.gov/books/NBK548583/
[9]
Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G. and PRISMA Group (2009) Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLOS MEDICINE, 6, e1000097. https://doi.org/10.1371/journal.pmed.1000097
[10]
Srinivasan, A., Dutta, P., Bansal, D., Chakrabarti, A., et al. (2021) Efficacy and Safety of Low-Dose Naltrexone in Painful Diabetic Neuropathy: A Randomized, Double-Blind, Active-Control, Crossover Clinical Trial. Journal of Diabetes, 13, 770-778. https://doi.org/10.1111/1753-0407.13202
[11]
Younger, J., Noor, N., McCue, R. and Mackey, S. (2013) Low-Dose Naltrexone for the Treatment of Fibromyalgia: Findings of a Small, Randomized, Double-Blind, Placebo-Controlled, Counterbalanced, Crossover Trial Assessing Daily Pain Levels. Arthritis Rheumatism, 65, 529-538. https://doi.org/10.1002/art.37734
[12]
Cree, B.A., Kornyeyeva, E. and Goodin, D.S. (2010) Pilot Trial of Low-Dose Naltrexone and Quality of Life in Multiple Sclerosis. Annals of Neurology, 68, 145-150. https://doi.org/10.1002/ana.22006
[13]
Sharafaddinzadeh, N., Moghtaderi, A., Kashipazha, D., Majdinasab, N. and Shalbafan, B. (2010) The Effect of Low-Dose Naltrexone on Quality of Life of Patients with Multiple Sclerosis: A Randomized Placebo-Controlled Trial. Multiple Sclerosis Journal, 16, 964-969. https://doi.org/10.1177/1352458510366857
[14]
Dieckmann, G., Ozmen, M.C., Cox, S.M., Engert, R.C. and Hamrah, P. (2021) Low-Dose Naltrexone Is Effective and Well-Tolerated for Modulating Symptoms in Patients with Neuropathic corneal Pain. The Ocular Surface, 20, 33-38. https://doi.org/10.1016/j.jtos.2020.12.003
[15]
Hamann, S. and Sloan, P. (2007) Oral Naltrexone to Enhance Analgesia in Patients Receiving Continuous Intrathecal Morphine for Chronic Pain: A Randomized, Double-Blind, Prospective Pilot Study. Journal of Opioid Management, 3, 137-144. https://doi.org/10.5055/jom.2007.0051
[16]
Bruun-Plesner, K., Blichfeldt-Eckhardt, M.R., Vaegter, H.B., Lauridsen, J.T., Amris, K. and Toft, P. (2020) Low-Dose Naltrexone for the Treatment of Fibromyalgia: Investigation of Dose-Response Relationships. Pain Medicine, 21, 2253-2261. https://doi.org/10.1093/pm/pnaa001
[17]
Gironi, M., Martinelli-Boneschi, F., Sacerdote, P., et al. (2008) A Pilot Trial of Low-Dose Naltrexone in Primary Progressive Multiple Sclerosis. Multiple Sclerosis Journal, 14, 1076-1083. https://doi.org/10.1177/1352458508095828
[18]
Metyas, S., Chen, C.L., Yeter, K., Solyman, J. and Arkfeld, D. (2018) Low Dose Naltrexone (LDN) for the Treatment of Chronic Pain. Journal of Clinical Rheumatology, 24, 44-48.
[19]
Webster, L.R., Butera, P.G., Moran, L.V., Wu, N., Burns, L.H. and Friedmann, N. (2006) Oxytrex Minimizes Physical Dependence While Providing Effective Analgesia: A Randomized Controlled Trial in Low Back Pain. The Journal of Pain, 7, 937-946. https://doi.org/10.1016/j.jpain.2006.05.005
