Melatonin analgesia is associated with improvement of the descending endogenous pain-modulating system in fibromyalgia: a phase II, randomized, double-dummy, controlled trial

Abstract

BackgroundCentral disinhibition is a mechanism involved in the physiopathology of fibromyalgia. Melatonin can improve sleep quality, pain and pain threshold. We hypothesized that treatment with melatonin alone or in combination with amitriptyline would be superior to amitriptyline alone in modifying the endogenous pain-modulating system (PMS) as quantified by conditional pain modulation (CPM), and this change in CPM could be associated with serum brain-derived neurotrophic factor (BDNF). We also tested whether melatonin improves the clinical symptoms of pain, pain threshold and sleep quality.MethodsSixty-three females, aged 18 to 65, were randomized to receive bedtime amitriptyline (25 mg) (n = 21), melatonin (10 mg) (n = 21) or melatonin (10 mg) + amitriptyline (25 mg) (n = 21) for a period of six weeks. The descending PMS was assessed with the CPM-TASK. It was assessed the pain score on the Visual Analog Scale (VAS 0-100 mm), the score on Fibromyalgia Impact Questionnaire (FIQ), heat pain threshold (HPT), sleep quality and BDNF serum. Delta values (post- minus pre-treatment) were used to compare the treatment effect. The outcomes variables were collected before, one and six weeks after initiating treatment.ResultsMelatonin alone or in combination with amitriptyline reduced significantly pain on the VAS compared with amitriptyline alone (P < 0.01). The delta values on the VAS scores were-12.85 (19.93),-17.37 (18.69) and-20.93 (12.23) in the amitriptyline, melatonin and melatonin+amitriptyline groups, respectively. Melatonin alone and in combination increased the inhibitory PMS as assessed by the Numerical Pain Scale [NPS(0-10)] reduction during the CPM-TASK:-2.4 (2.04) melatonin + amitriptyline,-2.65 (1.68) melatonin, and-1.04 (2.06) amitriptyline, (P < 0.05). Melatonin + amitriptyline treated displayed better results than melatonin and amitriptyline alone in terms of FIQ and PPT improvement (P < 0.05, fort both).ConclusionMelatonin increased the inhibitory endogenous pain-modulating system as assessed by the reduction on NPS(0-10) during the CPM-TASK. Melatonin alone or associated with amitriptyline was better than amitriptyline alone in improving pain on the VAS, whereas its association with amitriptyline produced only marginal additional clinical effects on FIQ and PPT.Trial registrationCurrent controlled trail is registered at clinical trials.gov upon under number NCT02041455. Registered January 16, 2014.

Current Understanding of Fibromyalgia: Diagnosis, Treatment, and Theories About Causes

“…In an RCT of women with FM (N = 63), mela- tonin alone (10 mg) or in combination with amitriptyline (25 mg) for 6 weeks, proved to be significantly more effective than melatonin or the antidepressant alone for reducing pain. 46 This result supported the researchers' hypothesis that melatonin increases the inhibitory endogenous painmodulating system involved in the pathophysiology of FM. Because there is a similarity in the symptoms of FM and magnesium deficiency, a pilot clinical trial is underway to study the effect of a transdermal magnesium chloride solution on patients' QoL.…”

Recent strategies for drug development in fibromyalgia syndrome

“…To study the effect of melatonin in FMS patients, de Zanette et al [27] performed a prospective, randomized trial comparing amitriptylene plus placebo, melatonin plus placebo and amitriptyline plus melatonin. There were 21 FMS patients in each group.…”

Current Treatments to Counter Sleep Dysfunction as a Pathogenic Stimulus of Fibromyalgia

“…In a control trial of melatonin in 63 patients with fibromyalgia, patients were randomized to receive 25 mg amitriptyline, 10 mg melatonin or a combination of both for 6 weeks [74]. Melatonin alone or in combination with amitriptyline reduced significantly pain and increased the inhibitory pain-modulating system as assessed by conditional pain modulation by hot heat task and pressure pain threshold.…”