title: Transcranial direct current stimulation (tDCS) reverts behavioral alterations and brainstem BDNF level increase induced by neuropathic pain model: Long-lasting effect.
abstract: BACKGROUND
  Neuropathic pain (NP) is a chronic pain modality that usually results of damage in the somatosensory system. NP often shows insufficient response to classic analgesics and remains a challenge to medical treatment. The transcranial direct current stimulation (tDCS) is a non-invasive technique, which induces neuroplastic changes in central nervous system of animals and humans. The brain derived neurotrophic factor plays an important role in synaptic plasticity process. Behavior changes such as decreased locomotor and exploratory activities and anxiety disorders are common comorbidities associated with NP.
  
  
  OBJECTIVE
  Evaluate the effect of tDCS treatment on locomotor and exploratory activities, and anxiety-like behavior, and peripheral and central BDNF levels in rats submitted to neuropathic pain model.
  
  
  METHODS
  Rats were randomly divided: Ss, SsS, SsT, NP, NpS, and NpT. The neuropathic pain model was induced by partial sciatic nerve compression at 14 days after surgery; the tDCS treatment was initiated. The animals of treated groups were subjected to a 20 minute session of tDCS, for eight days. The Open Field and Elevated Pluz Maze tests were applied 24 h (phase I) and 7 days (phase II) after the end of tDCS treatment. The serum, spinal cord, brainstem and cerebral cortex BDNF levels were determined 48 h (phase I) and 8 days (phase II) after tDCS treatment by ELISA.
  
  
  RESULTS
  The chronic constriction injury (CCI) induces decrease in locomotor and exploratory activities, increases in the behavior-like anxiety, and increases in the brainstem BDNF levels, the last, in phase II (one-way ANOVA/SNK, P<0.05 for all). The tDCS treatment already reverted all these effects induced by CCI (one-way ANOVA/SNK, P<0.05 for all). Furthermore, the tDCS treatment decreased serum and cerebral cortex BDNF levels and it increased these levels in the spinal cord in phase II (one-way ANOVA/SNK, P<0.05).
  
  
  CONCLUSIONS
  tDCS reverts behavioral alterations associated to neuropathic pain, indicating possible analgesic and anxiolytic tDCS effects. tDCS treatment induces changes in the BDNF levels in different regions of the central nervous system (CNS), and this effect can be attributed to different cellular signaling activations.
authors.affiliation: Post-Graduate Program in Medicine: Medical Sciences - Medicine School, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil; Pharmacology of Pain and Neuromodulation Laboratory: Pre-clinical Researches Department of Pharmacology, Universidade Federal do Rio Grande do Sul, ICBS, Porto Alegre, RS 90050-170, Brazil; Animal Experimentation Unit and Graduate Research Group, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS 90035-003, Brazil.
authors.forename: Paulo Ricardo Marques
authors.initials: PR
authors.lastname: Filho
authors.affiliation: Pharmacology of Pain and Neuromodulation Laboratory: Pre-clinical Researches Department of Pharmacology, Universidade Federal do Rio Grande do Sul, ICBS, Porto Alegre, RS 90050-170, Brazil; Animal Experimentation Unit and Graduate Research Group, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS 90035-003, Brazil; Post-Graduate Program in Biological Sciences - Physiology, Universidade Federal do Rio Grande do Sul, ICBS, Porto Alegre, RS 90050-170, Brazil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Vercelino
authors.affiliation: Post-Graduate Program in Medicine: Medical Sciences - Medicine School, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil; Pharmacology of Pain and Neuromodulation Laboratory: Pre-clinical Researches Department of Pharmacology, Universidade Federal do Rio Grande do Sul, ICBS, Porto Alegre, RS 90050-170, Brazil; Animal Experimentation Unit and Graduate Research Group, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS 90035-003, Brazil.
authors.forename: Stefania Giotti
authors.initials: SG
authors.lastname: Cioato
authors.affiliation: Pharmacology of Pain and Neuromodulation Laboratory: Pre-clinical Researches Department of Pharmacology, Universidade Federal do Rio Grande do Sul, ICBS, Porto Alegre, RS 90050-170, Brazil; Animal Experimentation Unit and Graduate Research Group, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS 90035-003, Brazil; Post-Graduate Program in Biological Sciences: Pharmacology and Experimental Therapeutic, Universidade Federal do Rio Grande do Sul, ICBS, Porto Alegre, RS 90050-170, Brazil.
authors.forename: Liciane Fernandes
authors.initials: LF
authors.lastname: Medeiros
authors.affiliation: Post-Graduate Program in Medicine: Medical Sciences - Medicine School, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil; Pharmacology of Pain and Neuromodulation Laboratory: Pre-clinical Researches Department of Pharmacology, Universidade Federal do Rio Grande do Sul, ICBS, Porto Alegre, RS 90050-170, Brazil; Animal Experimentation Unit and Graduate Research Group, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS 90035-003, Brazil.
authors.forename: Carla
authors.initials: C
authors.lastname: de Oliveira
authors.affiliation: Pharmacology of Pain and Neuromodulation Laboratory: Pre-clinical Researches Department of Pharmacology, Universidade Federal do Rio Grande do Sul, ICBS, Porto Alegre, RS 90050-170, Brazil; Animal Experimentation Unit and Graduate Research Group, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS 90035-003, Brazil; Post-Graduate Program in Biological Sciences - Physiology, Universidade Federal do Rio Grande do Sul, ICBS, Porto Alegre, RS 90050-170, Brazil.
authors.forename: Vanessa Leal
authors.initials: VL
authors.lastname: Scarabelot
authors.affiliation: Pharmacology of Pain and Neuromodulation Laboratory: Pre-clinical Researches Department of Pharmacology, Universidade Federal do Rio Grande do Sul, ICBS, Porto Alegre, RS 90050-170, Brazil.
authors.forename: Andressa
authors.initials: A
authors.lastname: Souza
authors.affiliation: Post-Graduate Program in Medicine: Medical Sciences - Medicine School, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil; Animal Experimentation Unit and Graduate Research Group, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS 90035-003, Brazil.
authors.forename: Joanna Ripoll
authors.initials: JR
authors.lastname: Rozisky
authors.affiliation: Pharmacology of Pain and Neuromodulation Laboratory: Pre-clinical Researches Department of Pharmacology, Universidade Federal do Rio Grande do Sul, ICBS, Porto Alegre, RS 90050-170, Brazil.
authors.forename: Alexandre da Silva
authors.initials: Ada S
authors.lastname: Quevedo
authors.affiliation: Post-Graduate Program in Medicine: Medical Sciences - Medicine School, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil; Pharmacology of Pain and Neuromodulation Laboratory: Pre-clinical Researches Department of Pharmacology, Universidade Federal do Rio Grande do Sul, ICBS, Porto Alegre, RS 90050-170, Brazil; Animal Experimentation Unit and Graduate Research Group, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS 90035-003, Brazil.
authors.forename: Lauren Naomi Spezia
authors.initials: LN
authors.lastname: Adachi
authors.affiliation: Biomedical Engineering of Hospital de Clínicas de Porto Alegre, Porto Alegre, RS 90035-003, Brazil.
authors.forename: Paulo Roberto S
authors.initials: PR
authors.lastname: Sanches
authors.affiliation: Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Felipe
authors.initials: F
authors.lastname: Fregni
authors.affiliation: Post-Graduate Program in Medicine: Medical Sciences - Medicine School, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil.
authors.forename: Wolnei
authors.initials: W
authors.lastname: Caumo
authors.affiliation: Post-Graduate Program in Medicine: Medical Sciences - Medicine School, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil; Pharmacology of Pain and Neuromodulation Laboratory: Pre-clinical Researches Department of Pharmacology, Universidade Federal do Rio Grande do Sul, ICBS, Porto Alegre, RS 90050-170, Brazil; Animal Experimentation Unit and Graduate Research Group, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS 90035-003, Brazil; Post-Graduate Program in Biological Sciences - Physiology, Universidade Federal do Rio Grande do Sul, ICBS, Porto Alegre, RS 90050-170, Brazil; Post-Graduate Program in Biological Sciences: Pharmacology and Experimental Therapeutic, Universidade Federal do Rio Grande do Sul, ICBS, Porto Alegre, RS 90050-170, Brazil. Electronic address: iracitorres@gmail.com.
authors.forename: Iraci L S
authors.initials: IL
authors.lastname: Torres
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology / Q000628:therapy; D001921:Brain / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005106:Exploratory Behavior / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D009437:Neuralgia / Q000503:physiopathology* / Q000628:therapy*; D011897:Random Allocation; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000293:injuries; D013116:Spinal Cord / Q000503:physiopathology; D065908:Transcranial Direct Current Stimulation / Q000379:methods*
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: Anxiety-like behavior; BDNF; Locomotor and exploratory activities; Neuropathic pain; Rats; Transcranial direct current stimulation (tDCS)