Younger, J., Parkitny, L., & McLain, D. (2014). The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clinical Rheumatology, 33(4), 451-459. https://doi.org/10.1007/s10067-014-2517-2
Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clinical Rheumatology. 2014;33(4):451-459. doi:10.1007/s10067-014-2517-2
Younger, Jarred, et al. "The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain." Clinical Rheumatology, vol. 33, no. 4, 2014, pp. 451-459.
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RRM Academy Synopsis
Low-dose naltrexone may ease chronic pain by calming microglia
A 2014 narrative review proposes that low-dose naltrexone may act as an anti-inflammatory agent by calming microglia. These are immune cells of the central nervous system, and the review draws on small trials in fibromyalgia, Crohn's disease and multiple sclerosis.
Key Findings
In a double-blind, crossover, counterbalanced study of 30 women with fibromyalgia, 57% of the participants had a significant pain reduction of one third during low-dose naltrexone.
An earlier single-blind pilot crossover trial found that low-dose naltrexone reduced fibromyalgia pain significantly more than placebo in 6 out of the 10 women.
In 38 people with fibromyalgia, higher baseline erythrocyte sedimentation rate tended to go with greater pain reduction on low-dose naltrexone (r = 0.58). Placebo showed no link (r = 0.06).
Crohn's disease studies reported significant improvement in over 80% of participants. The authors call the multiple sclerosis evidence less robust, with many endpoints no different from placebo.
Interpretation
The paper is a narrative review. The sedimentation rate analysis pools data across the fibromyalgia studies. Much of the animal and laboratory work used naloxone, a related compound, and the authors note that results may carry over imperfectly to naltrexone. They also describe a second explanation, an opioid rebound after brief receptor blockade, and state that both mechanisms may play a role. The authors conclude that more research is needed before the approach can be widely recommended.
RRM Context
Many chronic pain conditions involve inflammation with no known source. This review reflects research interest in how inflammation in the nervous system sustains pain. Restorative reproductive medicine looks for the cause of pelvic and other chronic pain, so work on how pain persists adds to that picture. The review itself addresses fibromyalgia and other conditions outside reproductive care.
Our editorial summary of this paper, not the article's abstract.
Abstract
Low-dose naltrexone (LDN) has been demonstrated to reduce symptom severity in conditions such as fibromyalgia, Crohn's disease, multiple sclerosis, and complex regional pain syndrome. We review the evidence that LDN may operate as a novel anti-inflammatory agent in the central nervous system, via action on microglial cells. These effects may be unique to low dosages of naltrexone and appear to be entirely independent from naltrexone's better-known activity on opioid receptors. As a daily oral therapy, LDN is inexpensive and well-tolerated. Despite initial promise of efficacy, the use of LDN for chronic disorders is still highly experimental. Published trials have low sample sizes, and few replications have been performed. We cover the typical usage of LDN in clinical trials, caveats to using the medication, and recommendations for future research and clinical work. LDN may represent one of the first glial cell modulators to be used for the management of chronic pain disorders.
