Pain Part 4 - less mainstream options - LDN and acupuncture

LDN from Johnson Compounding: https://naturalcompounder.com/compounding/low-dose-naltrexone/

LDN aka Low Dose Naltrexone has received some attention from the medical community, as it can help provide relief from chronic pain while reducing inflammation - and has been gaining popularity in Sjogren’s Syndrome treatment. From a review article de Carvalho JF, Skare T. Low-Dose Naltrexone in Rheumatological Diseases. Mediterr J Rheumatol. 2023 Mar 31;34(1):1-6. doi: 10.31138/mjr.34.1.1. PMID: 37223594; PMCID: PMC10201089.

In their introduction, they write:

“Low dose naltrexone (LDN) has been proposed as a new form of analgesic and anti-inflammatory treatment for several chronic pain conditions.1 This compound is functionally and structurally similar to the opioid antagonist naloxone, but with longer half-life and better oral bioavailability, and it is usually prescribed for treatment of opioid addiction.2 The typical dosage of naltrexone used for treatment of opioid addiction ranges from 50 to 100mg/day1; LDN refers to a dosage of 1–6 mg/day.2 At such low levels, naltrexone exhibits paradoxical anti-inflammatory and analgesic properties. The analgesic effect of LDN results from the blockage of mu- and delta-opioid receptors and to a lesser extent kappa-opioid receptors in the central nervous system leading to a feedback-mediated increase of these receptors and improving the endorphin system.1,3,4 The anti-inflammatory effects are due to blockage of the toll like receptor 4 (TLR-4) in the microglia cells, at central nervous system.5 These microglia cells, when chronically stimulated produce several pro-inflammatory cytokines, substance P, nitric oxide, and excitatory amino acids that are associated to the so-called sickness behaviour: cognitive impairment, mood and sleep disorders, fatigue, pain amplification and malaise, a group of symptoms similar to those found in patients with fibromyalgia (FM).1

LDN has been used as an alternative for treatment of several rheumatologic conditions such as FM, dermatomyositis and Sjögren’s syndrome.6–19” I should note that endorphins are our body’s own “opioids” which are capable of blocking pain and allowing our body’s to endure what some might term “superhuman” levels of exertion during exercise.

Since advanced dry eye conditions can result in chronic pain (including Sjogren’s Syndrome), I’ve begun to prescribe this medication for some and have been variably impressed by results. In this study compiling data from a broad base of published studies and case reports (which still resulted in small numbers of reported patient experiences), side effects ranged from mild gastrointestinal (abdominal pain, diarrhea) and minor insomnia and vivid dreams, to no side effects and results were at least equal to placebo (which can still be a significant positive). I should note that the side effects were reported in treatment of fibromyalgia patients and not for the Sjogren’s or other rheumatological treatments, so it isn’t clear if this shows a difference relatable to the spectrum of diseases or to the reporting.

Since inflammation is a common component of many diseases - including dry eye, it makes sense that any treatment resulting in less inflammation is likely to help. Unfortunately, LDN is not yet available through common pharmacies and as of this posting, must be ordered through “compounding pharmacies.” As such, it has yet to be covered by most health insurance companies and the compounding varies by the pharmacy producing it. One company I’ve used has a useful webpage on LDN and their compounding here: https://naturalcompounder.com/compounding/low-dose-naltrexone/ Because it can complicate treatment for those who might need opioids for greater levels of pain control and can trigger release of our body’s own forms of opioids, it is generally best to work alongside primary care physicians and may at times even require the expertise of pain specialists - so this form of treatment is still somewhat controversial and probably not appropriate for every dry eye sufferer.

While LDN is fairly “new age",” and can be “complicated,” acupuncture is definitely “old age” and perhaps less complicated. To assure that acupuncture has a place in relieving pain outside of Far Eastern Medicine, it is worth noting that it has found its way into military applications that include battlefield injuries: https://jts.health.mil/assets/docs/education/Battlefield_Acupuncture_Handbook.pdf

In a text covering the history of acupuncture A. White, E. Ernst, A brief history of acupuncture, Rheumatology, Volume 43, Issue 5, May 2004, Pages 662–663, https://doi.org/10.1093/rheumatology/keg005 an excerpt states:

“Acupuncture is generally held to have originated in China, being first mentioned in documents dating from a few hundred years leading up to the Common Era. Sharpened stones and bones that date from about 6000 bce have been interpreted as instruments for acupuncture treatment [1, 2], but they may simply have been used as surgical instruments for drawing blood or lancing abscesses [3]. Documents discovered in the Ma-Wang-Dui tomb in China, which was sealed in 198 bce, contain no reference to acupuncture as such [3], but do refer to a system of meridians, albeit very different from the model that was accepted later [4]. Speculation surrounds the tattoo marks seen on the ‘Ice Man’ who died in about 3300 bce and whose body was revealed when an Alpine glacier melted [5]. These tattoos might indicate that a form of stimulatory treatment similar to acupuncture developed quite independently of China.

The first document that unequivocally described an organized system of diagnosis and treatment which is recognized as acupuncture is The Yellow Emperor’s Classic of Internal Medicine, dating from about 100 bce. The information is presented in the form of questions by the Emperor and learned replies from his minister, Chhi-Po [6]. The text is likely to be a compilation of traditions handed down over centuries [7], presented in terms of the prevailing Taoist philosophy, and is still cited in support of particular therapeutic techniques [8]. The concepts of channels (meridians or conduits [3]) in which the Qi (vital energy or life force) flowed are well established by this time, though the precise anatomical locations of acupuncture points developed later [9]”

Focusing on the use in treating eye pain, an excellent review: Eye acupuncture for pain conditions: a scoping review of clinical studies - can be found here: https://pmc.ncbi.nlm.nih.gov/articles/PMC7989101/ While this does not look specifically at dry eyes and related eye pain, it does cover migraine and trigeminal nerve pain - which are common dry eye issues. These China-based studies found good efficacy with few side effects (with a few reports of fainting, dizziness, chest and abdominal discomfort). A dry eye specific report: “(This was) a prospective, randomized, double-blinded, sham-acupuncture-controlled study” can be found here: https://pmc.ncbi.nlm.nih.gov/articles/PMC6497118/#S0002 The conclusion of the article was: “Both true and sham acupuncture improved OSDI (a common means of scoring dry eye-related symptoms) at 1 week after treatment, however, the improvement in OSDI was significantly greater in the true treatment groups than the sham group at 6 months after acupuncture. True acupuncture treatment improved many subjective assessments of dry eye symptoms, however, other common indicators used to objectively assess dry eye (tear flow, corneal staining, TBUT) remained unchanged. While there were trends towards improvement in the sham acupuncture group, this did not reach statistical significant during the study period. This suggests a true treatment effect of acupuncture rather than a placebo effect. Acupuncture can, therefore, be an effective adjunct to routine clinical treatment of dry eye.”

While I have limited experience with either LDN or acupuncture for dry eye pain relief in my patient population, I remain open to novel treatments with a scientifically studied degree of safety and efficacy. Further research seems warranted and it is also worth noting that other integrative medicine and pharmacological approaches to pain continue to be researched and appear to show promise. I will be quick to share as I learn more!

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To schedule an appointment with Dr. Jaccoma, call Excellent Vision at either of these two dry eye offices:

(1) 155 Griffin Rd, Portsmouth, NH 03801 (603) 574-2020

(2) 3 Woodland Rd, STE 112 Stoneham, MA 02180 (near Boston) (781) 321-6463