www.elsevier.com/locate/brainres Available online at www.sciencedirect.com Research Report Reversal of chronic stress-induced pain by transcranial direct current stimulation (tDCS) in an animal model Lauren Naomi Spezia Adachi a,b,c , Wolnei Caumo a,b , Gabriela Laste a,b,c , Liciane Fernandes Medeiros a,c , Joanna Ripoll Rozisky a,b,c,d , Andressa de Souza a,b,c,d , Felipe Fregni d , Iraci L.S. Torres a,b,c,n Q1 a Pain Q11 Pharmacology and Neuromodulation, Animals Models Laboratory, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90050-170, Brazil b Graduate Program in Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil c Animal Experimentation Unit and Graduate Research Group, Hospital de Clı ´nicas de Porto Alegre, Porto Alegre, RS 90035-003, Brazil d Laboratory of Q12 Neuromodulation, Department of Physical Medicine & Rehabilitation, Spaulding Rehabilitation Hospital & Massachusetts General Hospital. Harvard Medical School and Center for Non-invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA article info Article history: Accepted 4 October 2012 Keywords: Chronic restraint stress Hyperalgesia Allodynia Transcranial direct current stimulation (tDCS) Neuromodulation TNFa abstract Transcranial direct current stimulation (tDCS) has been suggested as a therapeutic tool for pain syndromes. Although initial results in human subjects are encouraging, it still remains unclear whether the effects of tDCS can reverse maladaptive plasticity associated with chronic pain. To investigate this question, we tested whether tDCS can reverse the specific behavioral effects of chronic stress in the pain system, and also those indexed by corticosterone and interleukin-1b levels in serum and TNFa levels in the hippocampus, in a well-controlled rat model of chronic restraint stress (CRS). Forty-one adult male Wistar rats were divided into two groups control and stress. The stress group was exposed to CRS for 11 weeks for the establishment of hyperalgesia and mechanical allodynia as shown by the hot plate and von Frey tests, respectively. Rats were then divided into four groups control, stress, stressþsham tDCS and stressþtDCS. Anodal or sham tDCS was applied for 20 min/ day over 8 days and the tests were repeated. Then, the animals were killed, blood collected and hippocampus removed for ELISA testing. This model of CRS proved effective to induce chronic pain, as the animals exhibited hyperalgesia and mechanical allodynia. The hot plate test showed an analgesic effect, and the von Frey test, an anti-allodynic effect after the last tDCS session, and there was a significant decrease in hippocampal TNFa levels. BRES : 42581 Model7 pp:  3210ðcol:fig: : NILÞ 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 0006-8993/$ - see front matter & 2012 Published by Elsevier B.V. http://dx.doi.org/10.1016/j.brainres.2012.10.009 Abbreviations: tDCS, Transcranial direct current stimulation; CRS, chronic restraint stress; HPA, hypothalamic-pituitary-adrenal axis; HD-tDCS, High-definition tDCS; DC, direct current; IL1b, interleukin-1b; TNFa , tumor necrosis factor-a; BDNF, brain-derived neurotrophic factor; LTP, long-term potentiation n Corresponding author at: Departamento de Farmacologia – ICBS, UFRGS, Rua Sarmento Leite, 500 sala 202, Porto Alegre, RS 90050-170, Brazil. Fax: þ55 51 3308 3121. E-mail addresses: lauren_adachi@hotmail.com (L.N. Spezia Adachi), caumo@cpovo.net (W. Caumo), gabrielalaste@gmail.com (G. Laste), licimedeiros@hotmail.com (L. Fernandes Medeiros), joannarozisky@gmail.com (J. Ripoll Rozisky), andressasz@gmail.com (A. de Souza), fregni.felipe@mgh.harvard.edu (F. Fregni), iracitorres@gmail.com (I.L.S. Torres). brain research ] ( ]]]] ) ]]] – ]]] Please cite this article as: Spezia Adachi, L.N., et al., Reversal of chronic stress-induced pain by transcranial direct current stimulation (tDCS) in an animal model. Brain Research (2012), http://dx.doi.org/10.1016/j.brainres.2012.10.009