title: Top-Down Effect of Direct Current Stimulation on the Nociceptive Response of Rats.
abstract: Transcranial direct current stimulation (tDCS) is an emerging, noninvasive technique of neurostimulation for treating pain. However, the mechanisms and pathways involved in its analgesic effects are poorly understood. Therefore, we investigated the effects of direct current stimulation (DCS) on thermal and mechanical nociceptive thresholds and on the activation of the midbrain periaqueductal gray (PAG) and the dorsal horn of the spinal cord (DHSC) in rats; these central nervous system areas are associated with pain processing. Male Wistar rats underwent cathodal DCS of the motor cortex and, while still under stimulation, were evaluated using tail-flick and paw pressure nociceptive tests. Sham stimulation and naive rats were used as controls. We used a randomized design; the assays were not blinded to the experimenter. Immunoreactivity of the early growth response gene 1 (Egr-1), which is a marker of neuronal activation, was evaluated in the PAG and DHSC, and enkephalin immunoreactivity was evaluated in the DHSC. DCS did not change the thermal nociceptive threshold; however, it increased the mechanical nociceptive threshold of both hind paws compared with that of controls, characterizing a topographical effect. DCS decreased the Egr-1 labeling in the PAG and DHSC as well as the immunoreactivity of spinal enkephalin. Altogether, the data suggest that DCS disinhibits the midbrain descending analgesic pathway, consequently inhibiting spinal nociceptive neurons and causing an increase in the nociceptive threshold. This study reinforces the idea that the motor cortex participates in the neurocircuitry that is involved in analgesia and further clarifies the mechanisms of action of tDCS in pain treatment.
authors.affiliation: Laboratory of Neuromodulation and Experimental Pain, Hospital Sírio Libanês, Rua Prof Daher Cutait, 69, Sao Paulo, SP, 01308-060, Brazil.
authors.forename: Luiz Fabio
authors.initials: LF
authors.lastname: Dimov
authors.affiliation: Laboratory of Neuromodulation and Experimental Pain, Hospital Sírio Libanês, Rua Prof Daher Cutait, 69, Sao Paulo, SP, 01308-060, Brazil.
authors.forename: Adriano Cardozo
authors.initials: AC
authors.lastname: Franciosi
authors.affiliation: Laboratory of Neuromodulation and Experimental Pain, Hospital Sírio Libanês, Rua Prof Daher Cutait, 69, Sao Paulo, SP, 01308-060, Brazil.
authors.forename: Ana Carolina Pinheiro
authors.initials: AC
authors.lastname: Campos
authors.affiliation: Service of Interdisciplinary Neuromodulation (SIN), Department and Institute of Psychiatry, Faculty of Medicine of University of São Paulo, Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of São Paulo, Rua Doutor Ovidio Pires de Campos, 785, Sao Paulo, SP, 05403-000, Brazil.|Center for Clinical and Epidemiological Research & Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Avenida Professor Lineu Prestes 2565, ext. 3, Sao Paulo, SP, 05508-000, Brazil.
authors.forename: André Russowsky
authors.initials: AR
authors.lastname: Brunoni
authors.affiliation: Laboratory of Neuromodulation and Experimental Pain, Hospital Sírio Libanês, Rua Prof Daher Cutait, 69, Sao Paulo, SP, 01308-060, Brazil.
authors.forename: Rosana Lima
authors.identifier: http://orcid.org/0000-0002-5351-6575
authors.initials: RL
authors.lastname: Pagano
mesh_terms: D000818:Animals; D004566:Electrodes; D006930:Hyperalgesia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D008297:Male; D059225:Nociception; D010487:Periaqueductal Gray / Q000473:pathology / Q000503:physiopathology*; D020671:Posterior Horn Cells / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D065908:Transcranial Direct Current Stimulation