title: Melatonin analgesia is associated with improvement of the descending endogenous pain-modulating system in fibromyalgia: a phase II, randomized, double-dummy, controlled trial.
abstract: BACKGROUND
  Central 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.
  
  
  METHODS
  Sixty-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.
  
  
  RESULTS
  Melatonin 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).
  
  
  CONCLUSIONS
  Melatonin 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.
  
  
  BACKGROUND
  Current controlled trail is registered at clinical trials.gov upon under number NCT02041455. Registered January 16, 2014.
authors: Simone Azevedo
authors: SA
authors: de Zanette
authors: Rafael
authors: R
authors: Vercelino
authors: Gabriela
authors: G
authors: Laste
authors: Joanna Ripoll
authors: JR
authors: Rozisky
authors: André
authors: A
authors: Schwertner
authors: Caroline Buzzatti
authors: CB
authors: Machado
authors: Fernando
authors: F
authors: Xavier
authors: Izabel Cristina Custódio
authors: IC
authors: de Souza
authors: Alicia
authors: A
authors: Deitos
authors: Iraci L S
authors: IL
authors: Torres
authors: Pain and Palliative Care Service at the Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. caumo@cpovo.net.
authors: Wolnei
authors: W
authors: Caumo
mesh_terms: D000293:Adolescent; D000328:Adult; D000639:Amitriptyline / Q000008:administration & dosage / Q000627:therapeutic use; D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005356:Fibromyalgia / Q000150:complications*; D006801:Humans; D008550:Melatonin / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D010146:Pain / Q000150:complications / Q000188:drug therapy*; D011795:Surveys and Questionnaires; D064232:Visual Analog Scale; D055815:Young Adult
chemical_list: D000700:Analgesics; D019208:Brain-Derived Neurotrophic Factor; D000639:Amitriptyline; D008550:Melatonin