Topical Naltrexone helps with Corneal Neuropathy?



Topical Naltrexone helps with Corneal Neuropathy?

It may. 





Naltrexone is an opiate receptor antagonist and is long lasting. Low Dose Naltrexone (LDN) (4.5 mg daily) has been shown to block opioid receptors temporarily, which in turn leads to improved mood by enhancing endorphin and dopamine activity. It appears to increase β-endorphin, which is an opioid peptide with is known to affect pain modulation and mood via the hypothalamus, and on endocrine secretion.[1]


I have been prescribing LDN for about a year now in patients with corneal neuropathy with good results. It is NOT treating the underlying cause of pain, we think, but it is helping patients be able to not live in chronic pain in many cases. It is not a 100% guarantee but I have 3 patients that could not live without it. 

There is some hope that topical Naltrexone would also help and would avoid the negative side effects (though general mild) of LDN.

Here are some studies to show its benefit. 

Conclusion of below for Diabetic Ulcers on body:
0.03% NTX cream is comparable to standard care in preclinical studies

How they made it:
NTX was dissolved in sterile saline (v/v) for a final dosage of 0.03% NTX in Neutrogena moisturizing cream,





2016 Mar;32(2):127-32. doi: 10.1089/jop.2015.0070. Epub 2016 Jan 7.

Topical Application of Naltrexone to the Ocular Surface of Healthy Volunteers: A Tolerability Study.

Abstract

PURPOSE:

A short-term, randomized double-masked study was conducted to test the tolerability of topical application of naltrexone to the corneal surface.

METHODS:

Healthy human volunteers were recruited at the Penn State Hershey Medical Center between 2010 and 2013. Study groups of 4 subjects were established to receive escalating dosages of naltrexone; within each group, 1 subject received placebo. Four drops of 4 different dosages of naltrexone dissolved in commercial moxifloxacin solution were administered over a 24-h period of time; 1 group of subjects received only 1 drop. The naltrexone dosages tested were 1 × 10(-6) M (1 drop), 1 × 10(-6) M (4 drops), 5 × 10(-6) M (4 drops), 1 × 10(-5) M (4 drops), and 5 × 10(-5) M (4 drops). Drops were administered over a 24-h period. Consenting subjects had complete eye examinations, including visual acuity (ETDRS), external and slit-lamp examinations, corneal sensitivity, pachymetry, corneal topography, endothelial specular microscopy, Schirmer testing with anesthetic, and fundus photography, before receiving naltrexone. Individuals were reexamined at 24 h and 7 days following naltrexone or placebo application.

RESULTS:

Twenty subjects were recruited for the study; 62% were male, 90% were Caucasian; and 19 subjects completed the study. No significant differences were noted in ocular health between left (treated) and right (untreated) eyes of subjects receiving naltrexone or placebo. No significant adverse events were reported.

CONCLUSIONS:

Topical naltrexone was well tolerated in healthy human subjects after 1 or 4 eye drops of naltrexone at dosages up to 50 μM administered over a 24-h treatment period and observed for 1 week.


2014 Jun 1;3(6):419-427.

Topical Naltrexone as Treatment for Type 2 Diabetic Cutaneous Wounds.

Abstract

Objective: Type 2 diabetes (T2D) is associated with impaired cutaneous wound healing and can result in ulceration, infection, and/or amputation. More than 25 million people in the United States have T2D and are vulnerable to epithelial-related complications. Current therapies are limited in their efficacy. New treatments for full-thickness cutaneous wounds that focus on underlying diabetic pathways are needed. Approach: Topical application of the opioid receptor antagonist naltrexone (NTX) dissolved in cream reverses delayed wound closure in type 1 diabetic rat by the acceleration of reepithelialization and enhancement of angiogenesis and remodeling. NTX blocks the opioid growth factor (OGF)-OGF receptor (OGFr) axis and upregulates DNA synthesis and cell proliferation. To investigate whether NTX is an effective therapy for T2D wound closure, genetically obese mice (db/db) and normal C57Bl/6J mice received full-thickness cutaneous wounds. Wounds (5 mm in diameter) were treated topically three times daily with 10-5 M NTX or sterile saline dissolved in cream and photographed every 2 days. Results: Wounds in db/db mice treated with saline were 11-92% larger than those in normal mice throughout the 2-week observation. Topical NTX therapy in T2D mice reduced the residual wound size by 13-30% between days 8 and 14 relative to diabetic mice receiving saline. Reepithelialization and DNA synthesis, as analyzed by epithelial thickness and BrdU labeling indexes, respectively, were accelerated in NTX-treated wounds. Innovation and Conclusion: These data suggest that the OGF-OGFr axis plays a role in epithelial-related complications of T2D and that blockade of this pathway by NTX may be an effective treatment for wound repair.


References:
1. https://www-ncbi-nlm-nih-gov.ezp.welch.jhmi.edu/pmc/articles/PMC5592845/



Platelet-derived growth factor (PDGF)
https://regranex.com/mechanism-of-action

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