Transcranial Direct Current Stimulation (tDCS): What Pain Practitioners Need to Know
Transcranial direct current stimulation (tDCS) is a non-invasive, painless brain stimulation technique that is showing promise in the treatment of depression and chronic pain.1 tDCS is delivered through a battery-operated device that transfers electrical current of low intensity (1-2 mA) to the surface of the head, typically with 2 large (20-35 cm2) saline-soaked sponge-electrodes (Figure 1).
The primary mechanism of tDCS is a subthreshold modulation of neuronal resting membrane potential. In other words, the electrodes provide stimulation to specific areas of the brain for a few minutes, which results in neuroplasticity of glutamatergic synapses, and, thus, alterations of cortical excitability that last for 1 hour or more.2-4 There are 2 types of stimulation with tDCS: anodal and cathodal stimulation. The effects of tDCS on cortical excitability are polarity-dependent—anodal tDCS enhances activity, whereas cathodal tDCS diminishes excitability, if delivered within certain parameters.5,6
In addition, recent evidence suggests that tDCS interacts with various neurotransmitters in the brain, such as dopamine, acetylcholine, serotonin, and g-aminobutryic acid (GABA), and also can trigger changes in brain-derived neurotrophic factor (BDNF) that are associated with pain processing.7-12 Furthermore, research findings show that tDCS can upregulate and downregulate functional connectivity within brain networks, such as those that are important for cognitive, motor, and pain processing (Figure 2, page 60).13
These data, together with findings from other studies,14,15 have demonstrated that the neurophysiologic effects of tDCS are not limited to the area under the electrodes, providing evidence of activity alterations in distant interconnected cortical and subcortical areas.
These features make tDCS a promising tool for modulation of pain syndromes, which include pathological alterations of neural activity, excitability, and connectivity at multiple levels and sites of cerebral pain processing.16,17 Since reversal of maladaptive plasticity in the pain processing cerebral system has been shown to be associated with pain relief,18-20 the potential use of tDCS to prevent or reverse such maladaptive changes, or to enhance adaptive neuroplastic changes in the pain processing network is of high relevance for pain management.
However, the effects and functional outcomes of tDCS depend on a multitude of factors such as:
- The parameters of tDCS, (ie, delivered dose,21 including polarity of the current and position of the electrodes)
- Patient population and disease etiology
- Adjunct therapies and interventions
As neurophysiologic studies indicate, the brain state determined by chronic illness, and transient adjunct therapy, such as pharmacological intervention, profoundly influence outcomes.22,23 It is likely that other factors, many of them still unknown, contribute to shaping the effects of tDCS and defining patient responsiveness to this intervention.
Exploration in Pain Management
tDCS has been explored in a variety of pain populations with various conditions, including difficult-to-treat pain syndromes such as multiple sclerosis (MS)-related pain, fibromyalgia, complex regional pain syndrome, central pain due to spinal cord injury or stroke; as well as headaches, and acute post-
operative pain.24-32 The level of evidence for tDCS ranges from case reports to small-sample Phase II, randomized controlled trials in adult populations.
Critical reviews as well as meta-analyses of randomized controlled trials of tDCS in chronic pain reveal high variability of tDCS stimulation protocols.33,34 This is not unexpected given the diversity of tDCS dose, patient populations, disease etiology, and adjunct therapies. The most common electrode montages and stimulation parameters that yielded promising findings with respect to the analgesic effects of tDCS are described below.
Pain processing in the brain is not limited to one area or one sensory system. Therefore, the variety of electrode placements used in pain studies derives from the complexity of the cerebral pain processing neural network, which mediates vegetative, sensory-discriminative, affective, and cognitive aspects of pain. The vegetative and neuroendocrine effects of pain perception are linked, for the most part, to various subcortical regions, such as the amygdala or hypothalamus. The sensory-discriminative aspects of pain are covered by the spino-thalamic tract, the lateral thalamus, somatosensory areas, and the posterior insula, with the input from descending cortico-thalamic pathways originating in the motor cortex. Lastly, affective/cognitive processing of pain is related to the anterior insular and cingulate cortices, as well as the prefrontal areas of the brain.35-37
The pattern of current flow through the brain during tDCS (hence, which brain regions are targeted during stimulation) is determined by the configuration of the electrodes and the underlying brain anatomy. The operator can control the number of electrodes (typically ≥2), electrode assembly shape and size (typically 5 x 7 or 5 x 5 cm sponges), and the position of the electrodes on the body. Brain regions that are near the anode electrode are expected to increase their excitability, whereas regions near the cathode are expected to have decreased excitability. However, these relationships will vary with dose and brain state. In general, if the goal is increasing or decreasing brain function in a specific region, the anode or cathode, respectively, will be placed over that brain target and the other “return” electrode usually will be placed over the contralateral supra-orbital region.
Systems used to determine the electrode positioning vary; the most common is the International 10-20 EEG positioning system, but sophisticated electronic neuronavigational systems also are available. Reflecting the major components of the pain processing network, the main tDCS paradigms and electrode montages probed for analgesic effects include: