Low-Dose Naltrexone Applications in Chronic Pain and Inflammatory Disorders
Summary
Low-dose naltrexone (LDN), administered at 1–5 mg daily, has emerged as a novel modality for ameliorating symptoms in a range of chronic pain and inflammatory conditions. Unlike the higher 50 mg dose used in addiction, LDN exerts anti-inflammatory effects largely through transient blockade of opioid receptors, leading to rebound upregulation of endogenous opioids and attenuation of glial cell activation. Clinical experience and mechanistic investigations suggest that modulation of Toll-like receptor 4 signalling and reduction of proinflammatory cytokine release are central to its efficacy. The safety profile of LDN, coupled with low cost and minimal adverse events, has fostered interest in fibromyalgia, Crohn’s disease, multiple sclerosis and complex regional pain syndrome. Ongoing studies are exploring optimal dosing strategies, treatment duration and combination with standard therapies, while also probing biomarkers of response. The global burden of chronic pain and inflammatory disease underscores the potential for LDN to offer an accessible adjunctive option, with implications for reducing opioid use and improving quality of life.
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Low-Dose Naltrexone Applications in Chronic Pain and Inflammatory Disorders publication trend
The graph below shows the total number of articles in low-dose naltrexone applications in chronic pain and inflammatory disorders across all publications each year (not limited to Nature Index journals).
Technical terms
Glial cells: Non-neuronal cells in the central nervous system that mediate immune responses and inflammation.
Toll-like receptor 4 (TLR4): A pattern-recognition receptor on glia and immune cells that drives proinflammatory cytokine production.
Endogenous opioids: Naturally occurring peptides (e.g. endorphins) that bind opioid receptors to modulate pain and mood.
Ultra low-dose naltrexone (ULDN): Submicrogram dosing that enhances opioid analgesia via scaffolding proteins such as filamin A.
References
- Low-Dose Naltrexone (LDN)—Review of Therapeutic Utilization. Medical Sciences (2018).
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