title: Repetitive transcranial magnetic stimulation increases the corticospinal inhibition and the brain-derived neurotrophic factor in chronic myofascial pain syndrome: an explanatory double-blinded, randomized, sham-controlled trial.
abstract: Chronic myofascial pain syndrome has been related to defective descending inhibitory systems. Twenty-four females aged 19 to 65 years with chronic myofascial pain syndrome were randomized to receive 10 sessions of repetitive transcranial magnetic stimulation (rTMS) (n = 12) at 10 Hz or a sham intervention (n = 12). We tested if pain (quantitative sensory testing), descending inhibitory systems (conditioned pain modulation [quantitative sensory testing + conditioned pain modulation]), cortical excitability (TMS parameters), and the brain-derived neurotrophic factor (BDNF) would be modified. There was a significant interaction (time vs group) regarding the main outcomes of the pain scores as indexed by the visual analog scale on pain (analysis of variance, P < .01). Post hoc analysis showed that compared with placebo-sham, the treatment reduced daily pain scores by -30.21% (95% confidence interval = -39.23 to -21.20) and analgesic use by -44.56 (-57.46 to -31.67). Compared to sham, rTMS enhanced the corticospinal inhibitory system (41.74% reduction in quantitative sensory testing + conditioned pain modulation, P < .05), reduced the intracortical facilitation in 23.94% (P = .03), increased the motor evoked potential in 52.02% (P = .02), and presented 12.38 ng/mL higher serum BDNF (95% confidence interval = 2.32-22.38). No adverse events were observed. rTMS analgesic effects in chronic myofascial pain syndrome were mediated by top-down regulation mechanisms, enhancing the corticospinal inhibitory system possibly via BDNF secretion modulation.
  
  
  CONCLUSIONS
  High-frequency rTMS analgesic effects were mediated by top-down regulation mechanisms enhancing the corticospinal inhibitory, and this effect involved an increase in BDNF secretion.
authors.affiliation: Postgraduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Letizzia
authors.initials: L
authors.lastname: Dall'Agnol
authors.affiliation: Postgraduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Postgraduate Program in Biologic Sciences: Physiology, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Liciane Fernandes
authors.initials: LF
authors.lastname: Medeiros
authors.affiliation: Postgraduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Postgraduate Program in Biologic Sciences: Physiology, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Pharmacology Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Iraci L S
authors.initials: IL
authors.lastname: Torres
authors.affiliation: Postgraduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Alicia
authors.initials: A
authors.lastname: Deitos
authors.affiliation: Postgraduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Brietzke
authors.affiliation: Postgraduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Postgraduate Program in Biologic Sciences: Physiology, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Laste
authors.affiliation: Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Pain and Palliative Care Service at Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: Andressa
authors.initials: A
authors.lastname: de Souza
authors.affiliation: Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Júlia Lima
authors.initials: JL
authors.lastname: Vieira
authors.affiliation: Spaulding Center of Neuromodulation, Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts.
authors.forename: Felipe
authors.initials: F
authors.lastname: Fregni
authors.affiliation: Postgraduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Pharmacology Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Pain and Palliative Care Service at Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. Electronic address: caumo@cpovo.net.
authors.forename: Wolnei
authors.initials: W
authors.lastname: Caumo
mesh_terms: D000328:Adult; D000368:Aged; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D002908:Chronic Disease; D004311:Double-Blind Method; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007266:Inhibition, Psychological; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009209:Myofascial Pain Syndromes / Q000097:blood* / Q000188:drug therapy / Q000628:therapy*; D010147:Pain Measurement; D011712:Pyramidal Tracts / Q000502:physiology*; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000700:Analgesics; D019208:Brain-Derived Neurotrophic Factor
keywords: Myofascial pain syndrome; brain-derived neurotrophic factor; clinical trial; quantitative sensory testing; transcranial magnetic simulation