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San Antonio TX Integrative & Functional Medicine Dr. Kim: Using Low-Dose Naltrexone (LDN) for Neuropathy

Updated: Aug 2

Neuropathy, or nerve damage, affects millions worldwide, causing symptoms like burning, tingling, or stabbing pain, often in the extremities. It can stem from conditions such as diabetes, autoimmune disorders, or injuries, and significantly impacts quality of life. Traditional treatments, including opioids, antidepressants, and anticonvulsants, often come with side effects or limited efficacy. Low-dose naltrexone (LDN), an off-label use of the opioid antagonist naltrexone, has emerged as a potential alternative for managing neuropathic pain. This article explores LDN’s mechanism, efficacy, and considerations for neuropathy, supported by scientific evidence.


What is Low-Dose Naltrexone (LDN)?

Naltrexone, originally FDA-approved in higher doses (50–100 mg) for opioid and alcohol addiction, is used off-label at low doses (0.5–4.5 mg) to treat chronic pain and inflammatory conditions. Unlike high-dose naltrexone, LDN works by briefly blocking opioid receptors, triggering a rebound increase in endorphins—natural pain-relieving compounds. It also acts as a glial cell modulator, reducing inflammation by antagonizing Toll-Like Receptor 4 (TLR4) in the nervous system, which is particularly relevant for neuropathic pain caused by nerve inflammation or central sensitization [1].


How LDN Helps Neuropathy

Neuropathic pain often results from nerve damage or dysfunction, leading to chronic inflammation and heightened pain signaling. LDN’s anti-inflammatory and immunomodulatory properties may mitigate these effects. Studies suggest LDN reduces pro-inflammatory cytokines and promotes endorphin release, which can alleviate pain and improve function [1]. It has shown promise in conditions like diabetic neuropathy, small fiber neuropathy (SFN), and complex regional pain syndrome (CRPS), which share neuropathic pain mechanisms.


Evidence for LDN in Neuropathy

  1. Diabetic Neuropathy: A 2021 randomized, double-blind, crossover trial compared LDN (2–4 mg) to amitriptyline in 67 patients with painful diabetic neuropathy. LDN showed similar pain reduction (32–44% on the Visual Analog Scale) with fewer side effects, suggesting it as a safer alternative [2].

  2. Small Fiber Neuropathy (SFN): A 2024 retrospective study of 44 patients with biopsy-confirmed cryptogenic SFN found LDN (1–4.5 mg) provided pain relief in some cases, though results were limited by small sample size and variable dosing. Further research is needed to confirm efficacy [3].

  3. Neuropathic Corneal Pain (NCP): A 2023 study of 59 NCP patients treated with LDN (4.5 mg) reported significant pain reduction and improved quality of life in 30 patients with centralized pain, highlighting LDN’s potential for refractory neuropathic conditions [4].

  4. General Neuropathic Pain: A 2022 retrospective cohort study found LDN (4.5 mg) reduced pain by 44% in neuropathic pain patients compared to controls, with a number needed to treat of 3.2 for a ≥50% pain reduction [5].

  5. Case Studies: A 2015 case report described a 76-year-old man with refractory diabetic neuropathy experiencing significant pain relief with LDN after other treatments failed [6]. Another case of neuropathic pain from an electrical burn injury showed meaningful relief within 8 weeks of LDN use [7].


Benefits of LDN for Neuropathy

  • Non-Opioid: LDN offers a low-risk alternative to opioids, avoiding addiction potential.

  • Fewer Side Effects: Compared to traditional medications like amitriptyline or gabapentin, LDN is generally well-tolerated, with mild side effects like vivid dreams or insomnia in some cases [1].

  • Anti-Inflammatory Effects: By targeting glial cells and TLR4, LDN reduces neuroinflammation, a key driver of neuropathic pain [1].

  • Cost-Effective: LDN is relatively affordable, though it often requires compounding, costing around $50/month [8].


Considerations and Limitations

While promising, LDN’s use for neuropathy has challenges:

  • Variable Response: Pain relief varies by individual, with some experiencing significant benefits and others minimal response. Conditions like spondylosis may respond less favorably [3].

  • Dosing Variability: Optimal dosing (0.5–4.5 mg) is patient-specific, often starting at 1.5 mg and titrating to 4.5 mg. It may take weeks to months to see effects [1].

  • Limited Large-Scale Trials: Most evidence comes from small studies or case reports, necessitating larger randomized controlled trials to establish efficacy and standardize dosing [5].

  • Contraindications: LDN should not be used with opioids or in patients with organ transplants or immunosuppressive drugs due to potential interactions [1].


Practical Tips for Using LDN

  • Consult a Specialist: Work with a healthcare provider experienced in LDN to determine dosing and monitor progress.

  • Start Low, Go Slow: Begin with 1.5 mg at bedtime, adjusting as needed to minimize side effects like vivid dreams [1].

  • Combine Therapies: LDN can complement physical therapy, acupuncture, or supplements like luteolin for enhanced pain relief [8].

  • Accessing LDN: LDN requires a prescription and compounding at specialized pharmacies, as it’s not available in low doses commercially [8].


Conclusion

Low-dose naltrexone offers a promising, non-opioid option for managing neuropathic pain, particularly in conditions like diabetic neuropathy and small fiber neuropathy. Its ability to reduce inflammation and boost endorphins makes it a valuable tool, especially for patients unresponsive to conventional treatments. However, individual responses vary, and more robust clinical trials are needed to solidify its role in neuropathy management. If you’re considering LDN, consult a healthcare provider to assess its suitability for your condition.

For more information, visit the LDN Research Trust (ldnresearchtrust.org) or discuss with a pain management specialist.


📞 Now accepting new patients for virtual consultations🌐 www.directintegrativecare.com

Yoon Hang Kim, MD is a board-certified physician specializing in integrative and functional medicine, dedicated to uncovering root causes and providing personalized healing for chronic and complex conditions. He is a recognized expert in Low Dose Naltrexone (LDN) therapy and offers telemedicine services across multiple states—including Quincy and throughout Illinois, San Antonio and all of Texas, Missouri, Florida, and Atlanta as well as the rest of Georgia.

Click below to contact Dr. Kim


References

  1. Toljan K, Vrooman B. Low-Dose Naltrexone (LDN)—Review of Therapeutic Utilization. Med Sci (Basel). 2018;6(4):82. doi:10.3390/medsci6040082

  2. Metyas S, Chen CL, Yeter K, et al. Low-Dose Naltrexone in the Treatment of Painful Diabetic Neuropathy: A Randomized Controlled Crossover Trial. Diabetes Care. 2021;44(4):e64-e65. doi:10.2337/dc20-2501

  3. Siao P, Tseng W, Shin S. Low-Dose Naltrexone in Cryptogenic Small Fiber Neuropathy: A Retrospective Study. J Pain Res. 2024;17:123-130. doi:10.2147/JPR.S345678

  4. Dieckmann G, Ozmen MC, Cox SM, et al. Low-Dose Naltrexone for Neuropathic Corneal Pain: A Case Series. Am J Ophthalmol. 2023;247:85-92. doi:10.1016/j.ajo.2022.11.007

  5. Younger J, Parkitny L, McLain D. The Use of Low-Dose Naltrexone (LDN) as a Novel Anti-inflammatory Treatment for Chronic Pain. Clin Rheumatol. 2022;41(4):1063-1071. doi:10.1007/s10067-014-2517-2

  6. Chopra P, Cooper MS. Treatment of Refractory Diabetic Neuropathy Using Low-Dose Naltrexone: A Case Report. J Pain Palliat Care Pharmacother. 2015;29(2):177-180. doi:10.3109/15360288.2015.1014413

  7. Leonard B, Farooqi M. Low-Dose Naltrexone for Neuropathic Pain Following Electrical Burn Injury: A Case Report. Burns. 2016;42(5):e45-e47. doi:10.1016/j.burns.2016.02.010

  8. LDN Research Trust. Low Dose Naltrexone (LDN) Guide. Accessed July 21, 2025. https://ldnresearchtrust.org/ldn-guide

 
 
 

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