title: Long-Lasting Effect of Transcranial Direct Current Stimulation in the Reversal of Hyperalgesia and Cytokine Alterations Induced by the Neuropathic Pain Model.
abstract: BACKGROUND
  Neuropathic pain (NP) is caused by an insult or dysfunction in the peripheral or central nervous system (CNS), the main symptoms being mechanical allodynia and hyperalgesia. NP often shows insufficient response to classic analgesics and its management remains a challenge. Transcranial direct current stimulation (tDCS) is a non-invasive method of cerebral stimulation and represents a promising resource for pain management.
  
  
  OBJECTIVE
  We investigated the effects of tDCS on the nociceptive response and on IL-1β, IL-10, and TNF-α levels in CNS structures of rats with NP.
  
  
  METHODS
  After induction of NP by chronic constriction injury (CCI) of the sciatic nerve, the rats received 20 min of bicephalic tDCS for 8 days. Hyperalgesia was assessed by the hot plate and von Frey tests and evaluated at baseline, 7 days, and 14 days after CCI surgery, and also immediately, 24 hours, and 7 days following tDCS treatment. The levels of IL-1β, IL-10 and TNF-α in the cortex, spinal cord, and brainstem were determined by ELISA at 48 hours and 7 days post-tDCS.
  
  
  RESULTS
  The CCI model provoked thermal and mechanical hyperalgesia until at least 30 days post-CCI; however, bicephalic tDCS relieved the nociceptive behavior for up to 7 days after treatment completion.
  
  
  CONCLUSIONS
  Bicephalic tDCS is effective to promote antinociceptive behavior in neuropathic pain, which can be reflected by a spinal neuroimmunomodulation linked to pro- and anti-inflammatory cytokine levels observed in the long-term.
authors.affiliation: Graduate Program in Medicine - Medical Sciences, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, Brazil; Laboratory of Pharmacology of Pain and Neuromodulation - Animal Models, Department of Pharmacology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90050-170 Porto Alegre, Brazil; Animal Experimentation Unit, Graduate Research Group, Hospital de Clínicas de Porto Alegre, 90035-003 Porto Alegre, Brazil.
authors.forename: Stefania Giotti
authors.initials: SG
authors.lastname: Cioato
authors.affiliation: Laboratory of Pharmacology of Pain and Neuromodulation - Animal Models, Department of Pharmacology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90050-170 Porto Alegre, Brazil; Animal Experimentation Unit, Graduate Research Group, Hospital de Clínicas de Porto Alegre, 90035-003 Porto Alegre, Brazil.
authors.forename: Liciane Fernandes
authors.initials: LF
authors.lastname: Medeiros
authors.affiliation: Graduate Program in Medicine - Medical Sciences, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, Brazil; Laboratory of Pharmacology of Pain and Neuromodulation - Animal Models, Department of Pharmacology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90050-170 Porto Alegre, Brazil; Animal Experimentation Unit, Graduate Research Group, Hospital de Clínicas de Porto Alegre, 90035-003 Porto Alegre, Brazil.
authors.forename: Paulo Ricardo
authors.initials: PR
authors.lastname: Marques Filho
authors.affiliation: Graduate Program in Biological Sciences - Physiology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90050-170 Porto Alegre, Brazil; Laboratory of Pharmacology of Pain and Neuromodulation - Animal Models, Department of Pharmacology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90050-170 Porto Alegre, Brazil; Animal Experimentation Unit, Graduate Research Group, Hospital de Clínicas de Porto Alegre, 90035-003 Porto Alegre, Brazil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Vercelino
authors.affiliation: Graduate Program in Medicine - Medical Sciences, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, Brazil; Laboratory of Pharmacology of Pain and Neuromodulation - Animal Models, Department of Pharmacology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90050-170 Porto Alegre, Brazil; Animal Experimentation Unit, Graduate Research Group, Hospital de Clínicas de Porto Alegre, 90035-003 Porto Alegre, Brazil.
authors.forename: Andressa
authors.initials: A
authors.lastname: de Souza
authors.affiliation: Graduate Program in Biological Sciences - Physiology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90050-170 Porto Alegre, Brazil; Laboratory of Pharmacology of Pain and Neuromodulation - Animal Models, Department of Pharmacology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90050-170 Porto Alegre, Brazil; Animal Experimentation Unit, Graduate Research Group, Hospital de Clínicas de Porto Alegre, 90035-003 Porto Alegre, Brazil.
authors.forename: Vanessa Leal
authors.initials: VL
authors.lastname: Scarabelot
authors.affiliation: Graduate Program in Medicine - Medical Sciences, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, Brazil; Laboratory of Pharmacology of Pain and Neuromodulation - Animal Models, Department of Pharmacology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90050-170 Porto Alegre, Brazil; Animal Experimentation Unit, Graduate Research Group, Hospital de Clínicas de Porto Alegre, 90035-003 Porto Alegre, Brazil.
authors.forename: Carla
authors.initials: C
authors.lastname: de Oliveira
authors.affiliation: Graduate Program in Medicine - Medical Sciences, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, Brazil; Laboratory of Pharmacology of Pain and Neuromodulation - Animal Models, Department of Pharmacology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90050-170 Porto Alegre, Brazil; Animal Experimentation Unit, Graduate Research Group, Hospital de Clínicas de Porto Alegre, 90035-003 Porto Alegre, Brazil.
authors.forename: Lauren Naomi Spezia
authors.initials: LN
authors.lastname: Adachi
authors.affiliation: Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Felipe
authors.initials: F
authors.lastname: Fregni
authors.affiliation: Graduate Program in Medicine - Medical Sciences, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, Brazil; Laboratory of Pharmacology of Pain and Neuromodulation - Animal Models, Department of Pharmacology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90050-170 Porto Alegre, Brazil; Animal Experimentation Unit, Graduate Research Group, Hospital de Clínicas de Porto Alegre, 90035-003 Porto Alegre, Brazil.
authors.forename: Wolnei
authors.initials: W
authors.lastname: Caumo
authors.affiliation: Graduate Program in Medicine - Medical Sciences, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, Brazil; Graduate Program in Biological Sciences - Physiology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90050-170 Porto Alegre, Brazil; Laboratory of Pharmacology of Pain and Neuromodulation - Animal Models, Department of Pharmacology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90050-170 Porto Alegre, Brazil; Animal Experimentation Unit, Graduate Research Group, Hospital de Clínicas de Porto Alegre, 90035-003 Porto Alegre, Brazil. Electronic address: iracitorres@gmail.com.
authors.forename: Iraci L S
authors.initials: IL
authors.lastname: Torres
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D006930:Hyperalgesia / Q000276:immunology / Q000378:metabolism* / Q000523:psychology / Q000628:therapy*; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D009437:Neuralgia / Q000276:immunology / Q000378:metabolism* / Q000523:psychology / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000293:injuries; D013116:Spinal Cord / Q000378:metabolism; D065908:Transcranial Direct Current Stimulation / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: Bicephalic; Cytokines; Hyperalgesia; Neuropathic pain; tDCS