title: Electroacupuncture analgesia is associated with increased serum brain-derived neurotrophic factor in chronic tension-type headache: a randomized, sham controlled, crossover trial.
abstract: BACKGROUND
  Chronic tension-type headache (CTTH) is characterized by almost daily headaches and central sensitization, for which electroacupuncture (EA) might be effective. The central nervous system (CNS) plasticity can be tracked in serum using the brain-derived neurotrophic factor (BDNF), a neuroplasticity mediator. Thus, we tested the hypothesis that EA analgesia in CTTH is related to neuroplasticity indexed by serum BDNF.
  
  
  METHODS
  We enrolled females aged 18-60 years with CTTH in a randomized, blinded, placebo-controlled crossover trial, comparing ten EA sessions applied for 30 minutes (2-10 Hz, intensity by tolerance) in cervical areas twice per week vs. a sham intervention. Treatment periods were separated by two washout weeks. Pain on the 10-cm visual analog scale (VAS) and serum BDNF were assessed as primary outcomes.
  
  
  RESULTS
  Thirty-four subjects underwent randomization, and twenty-nine completed the protocol. EA was superior to sham to alleviate pain (VAS scores 2.38 ± 1.77 and 3.02 ± 2.49, respectively, P = 0.005). The VAS scores differed according to the intervention sequence, demonstrating a carryover effect (P < 0.05). Using multiple regression, serum BDNF was adjusted for the Hamilton depression rating scale (HDRS) and the VAS scores (r-squared = 0.07, standard β coefficients = -0.2 and -0.14, respectively, P < 0.001). At the end of the first intervention period, the adjusted BDNF was higher in the EA phase (29.31 ± 3.24, 27.53 ± 2.94 ng/mL, Cohen's d = 0.55).
  
  
  CONCLUSIONS
  EA analgesia is related to neuroplasticity indexed by the adjusted BDNF. EA modulation of pain and BDNF occurs according to the CNS situation at the moment of its administration, as it was related to depression and the timing of its administration.
authors.affiliation: Post-Graduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. monicachassot@hotmail.com.|Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre at UFRGS, Rua Ramiro Barcelos, 2350 - CEP 90035-003 Bairro Rio Branco, Porto, Brazil. monicachassot@hotmail.com.
authors.forename: Mônica
authors.initials: M
authors.lastname: Chassot
authors.affiliation: Post-Graduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. jadussans@gmail.com.|Pain and Palliative Care Service at Hospital de Clínicas de Porto Alegre (HCPA), UFRGS, Porto Alegre, Brazil. jadussans@gmail.com.|Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre at UFRGS, Rua Ramiro Barcelos, 2350 - CEP 90035-003 Bairro Rio Branco, Porto, Brazil. jadussans@gmail.com.
authors.forename: Jairo Alberto
authors.initials: JA
authors.lastname: Dussan-Sarria
authors.affiliation: Post-Graduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. francisehn@ibest.com.br.|Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre at UFRGS, Rua Ramiro Barcelos, 2350 - CEP 90035-003 Bairro Rio Branco, Porto, Brazil. francisehn@ibest.com.br.
authors.forename: Francislea Cristina
authors.initials: FC
authors.lastname: Sehn
authors.affiliation: Post-Graduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. aliciadeitos@gmail.com.|Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre at UFRGS, Rua Ramiro Barcelos, 2350 - CEP 90035-003 Bairro Rio Branco, Porto, Brazil. aliciadeitos@gmail.com.
authors.forename: Alícia
authors.initials: A
authors.lastname: Deitos
authors.affiliation: Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre at UFRGS, Rua Ramiro Barcelos, 2350 - CEP 90035-003 Bairro Rio Branco, Porto, Brazil. andressasz@gmail.com.|Post-Graduate Program in Health and Human Development, Unilasalle Universitary Center, Canoas, Brazil. andressasz@gmail.com.
authors.forename: Andressa
authors.initials: A
authors.lastname: de Souza
authors.affiliation: Post-Graduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. rvercelino@gmail.com.|Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre at UFRGS, Rua Ramiro Barcelos, 2350 - CEP 90035-003 Bairro Rio Branco, Porto, Brazil. rvercelino@gmail.com.
authors.forename: Rafael
authors.initials: R
authors.lastname: Vercelino
authors.affiliation: Post-Graduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. iracitorres@gmail.com.|Pharmacology Department, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, Brazil. iracitorres@gmail.com.
authors.forename: Iraci L S
authors.initials: IL
authors.lastname: Torres
authors.affiliation: Spaulding Center of Neuromodulation, Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts, USA. felipe.fregni@gmail.com.
authors.forename: Felipe
authors.initials: F
authors.lastname: Fregni
authors.affiliation: Post-Graduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. caumo@cpovo.net.|Pain and Palliative Care Service at Hospital de Clínicas de Porto Alegre (HCPA), UFRGS, Porto Alegre, Brazil. caumo@cpovo.net.|Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre at UFRGS, Rua Ramiro Barcelos, 2350 - CEP 90035-003 Bairro Rio Branco, Porto, Brazil. caumo@cpovo.net.|Surgery Department, School of Medicine at UFRGS, Porto Alegre, Brazil. caumo@cpovo.net.
authors.forename: Wolnei
authors.initials: W
authors.lastname: Caumo
mesh_terms: D015667:Acupuncture Analgesia; D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D002490:Central Nervous System / Q000502:physiology; D018592:Cross-Over Studies; D003863:Depression / Q000150:complications; D015671:Electroacupuncture; D005260:Female; D006801:Humans; D008875:Middle Aged; D059408:Pain Management / Q000379:methods*; D010147:Pain Measurement; D018781:Tension-Type Headache / Q000097:blood / Q000628:therapy*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human