Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Sep 28;11(9):e40025.
doi: 10.2196/40025.

Melatonin for Neuropathic Pain: Protocol for a Double-blind, Randomized Controlled Trial

Ian Gilron  1 , Dongsheng Tu  2 , Ronald R Holden  2 , Dwight E Moulin  3 , Scott Duggan  1 , Roumen Milev  2
Affiliations

Melatonin for Neuropathic Pain: Protocol for a Double-blind, Randomized Controlled Trial

Ian Gilron et al. JMIR Res Protoc. .

Abstract

Background: Neuropathic pain (NP), a complication of several conditions (eg, diabetic neuropathy and varicella zoster), is a common challenging problem, and there is a growing need to develop safe and effective nonopioid treatments. Sleep disturbance is commonly associated with NP because pain intensity in NP conditions is often worse at night. The pineal hormone melatonin has been shown to reduce pain in both preclinical and clinical settings, in addition to multiple trials demonstrating efficacy for primary insomnia and delayed sleep phase syndrome.

Objective: We propose to conduct a clinical trial to evaluate the efficacy and safety of melatonin for NP.

Methods: Using a double-blind, placebo-controlled, crossover design, 30 adults with NP will be randomly allocated to one of two sequences of treatment with melatonin and placebo. During each of the two treatment periods, participants will take capsules containing melatonin or placebo for 4 weeks, followed by a 7-day washout period. The primary outcome will be mean daily pain intensity (scored 0-10) at maximally tolerated doses (MTDs) during each period. Secondary outcomes, assessed at MTDs, will include global improvement, adverse events, mood, and quality of life.

Results: This trial was registered in the International Standard Randomized Controlled Trial registry May 4, 2022 (ISRCTN #16215617), attained conditional ethics approval May 9, 2022 (Queen's University Health Sciences & Affiliated Teaching Hospitals Research Ethics Board protocol number ANAE-387-22), and recruitment is set to start August 2022.

Conclusions: This trial will provide rigorous evidence comparing the efficacy of melatonin to that of placebo in the treatment of NP.

Trial registration: ISRCTN Registry 16215617; https://www.isrctn.com/ISRCTN16215617.

International registered report identifier (irrid): PRR1-10.2196/40025.

Keywords: analgesic therapy; chronic pain; clinical; clinical trials; efficacy; insomnia; melatonin; neuropathic; neuropathic pain; nonopioid; pain; placebo; preclinical; sleep; treatment.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: IG reports receiving personal fees from Adynxx, Biogen, Eupraxia, Novaremed, and Teva outside the submitted work. DEM reports receiving personal fees from Canopy Growth outside the submitted work. RM reports receiving consulting and speaking honoraria from AbbVie, Allergan, Eisai, Janssen, KYE Pharmaceuticals, Lallemand, Lundbeck, Neonmind, Otsuka, and Sunovion, and research grants from Canadian Biomarker Integration Network in Depression, Canadian Institutes of Health Research, Janssen, Lallemand, Lundbeck, Nubiyota, Ontario Brain Institute, and Ontario Mental Health Foundation. He owns shares of Neonmind Inc.

Figures

Figure 1
Figure 1
Clinical Trial Schema.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Jensen TS, Baron R, Haanpää M, Kalso E, Loeser JD, Rice ASC, Treede R. A new definition of neuropathic pain. Pain. 2011 Oct;152(10):2204–2205. doi: 10.1016/j.pain.2011.06.017.00006396-201110000-00008 - DOI - PubMed
    1. Scholz J, Finnerup NB, Attal N, Aziz Q, Baron R, Bennett MI, Benoliel R, Cohen M, Cruccu G, Davis KD, Evers S, First M, Giamberardino MA, Hansson P, Kaasa S, Korwisi B, Kosek E, Lavand'homme P, Nicholas M, Nurmikko T, Perrot S, Raja SN, Rice ASC, Rowbotham MC, Schug S, Simpson DM, Smith BH, Svensson P, Vlaeyen JWS, Wang S, Barke A, Rief W, Treede R, Classification Committee of the Neuropathic Pain Special Interest Group (NeuPSIG) The IASP classification of chronic pain for ICD-11: chronic neuropathic pain. Pain. 2019 Jan;160(1):53–59. doi: 10.1097/j.pain.0000000000001365. https://europepmc.org/abstract/MED/30586071 00006396-201901000-00007 - DOI - PMC - PubMed
    1. van Hecke O, Austin SK, Khan RA, Smith BH, Torrance N. Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain. 2014 Apr;155(4):654–662. doi: 10.1016/j.pain.2013.11.013.00006396-201404000-00004 - DOI - PubMed
    1. O'Connor AB. Neuropathic pain: quality-of-life impact, costs and cost effectiveness of therapy. Pharmacoeconomics. 2009;27(2):95–112. doi: 10.2165/00019053-200927020-00002.2 - DOI - PubMed
    1. Smith BH, Torrance N. Epidemiology of neuropathic pain and its impact on quality of life. Curr Pain Headache Rep. 2012 Jun;16(3):191–198. doi: 10.1007/s11916-012-0256-0. - DOI - PubMed