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.
Highlights
Transcranial direct current stimulation is a noninvasive brain stimulation technique with promising clinical outcomes for various conditions, including Parkinson’s disease [1], stroke [2], multiple sclerosis [3], schizophrenia [4], major depression [5] and pain [6]
The analgesia induced by Transcranial direct current stimulation (tDCS) when applied over the primary motor cortex (M1) has been attributed to modulation of areas associated with pain processing, including the anterior cingulate, insula, thalamic nuclei and upper brainstem [9,20,21,22,23,24,25], as well as to regulation of glutamate, GABA and opioid activity, which results in the activation of descending analgesic pathways [25,26,27,28]
The results obtained in the nociceptive tests, before electrode implantation in the basal measurement, were equal to the data observed after 5 days of the surgical procedure, showing that the increase of nociceptive threshold after the direct current stimulation (DCS) was a consequence of the electrical stimulation
Summary
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique with promising clinical outcomes for various conditions, including Parkinson’s disease [1], stroke [2], multiple sclerosis [3], schizophrenia [4], major depression [5] and pain [6]. This approach is relatively safe, well tolerated, affordable and deployable and consists of the application of a weak electric current to the scalp via two electrodes (anode and cathode); its efficacy depends critically on parameters such as electrode position and current strength [7]. Both anodal and cathodal tDCS are known to increase the nociceptive threshold in healthy subjects [22,44,45,46,47]; until now, no experimental studies have been conducted to evaluate the cathodal DCS-induced antinociception in naive rats to better understand the neurocircuitry that mediates this response
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