**4. Translation for patient pain relief ?**

Early studies using tDCS in patient studies have had variable success and lack strong evidence of treatment efficacy [61]. Initial randomized controlled trials of anodal tDCS to primary motor cortex (M1) as an intervention for neuropathic pain found the intervention to be ineffective [62]. However, recent studies provide support for tDCS of M1 as a treatment intervention for knee osteoarthritis [63], fibromyalgia [64] and inflammatory bowel disease [29]. There have also been randomized clinical trials using prefrontal tDCS demonstrating tDCS to be effective in pain reduction in patients with multiple sclerosis [65] and fibromyalgia [49] and also reduce post-surgical opioid use [66]. A recent meta-analysis of selected randomized controlled trials of tDCS for non-cancer pain included predominantly M1 tDCS but also left dorsolateral prefrontal tDCS [48]. The meta-analysis showed active stimulation was consistently better than sham stimulation with stronger evidence for the efficacy of anodal M1 tDCS [48]. However, overall there remain shortcomings in the current literature on tDCS in patient groups; the study numbers are

**197**

**clinic**

*From Mechanisms to Analgesia: Towards the Use of Non-Invasive Neuromodulation for Pain…*

with standardized protocols and patient cohorts are necessary.

small; the tDCS protocols differ across studies; the patient groups are heterogeneous making meta-analysis challenging; and the study designs used inconsistent, with some studies favoring a cross-over design to a control group. For tDCS to become an established treatment intervention, large multi-centre randomized controlled trials

Studies using VNS in patient groups report beneficial effects of this form of stimulation in patients with pain associated with inflammatory conditions, for instance rheumatoid arthritis or migraine. Indeed recent studies have provided strong support for the use of vagal nerve stimulation in arthritis patients [56]. The combination of anti-inflammatory effects of VNS [67] with the previously mentioned analgesic effects via the endogenous opioid system may explain the potential for this technique in these patient groups. In fibromyalgia, although the disease etiology is uncertain, patients are known to experience systemic inflammation and neuroinflammation, and so may be a patient group that particularly benefits from this intervention.

**5. Methodology for translation of electric current stimulation to the** 

Evidence for the efficacy of non-invasive application of electric currents in humans for neuromodulatory effects has been rapidly increasing, with many proposed applications, including pain. The potential applications explored have been extensive as the technique is easy to implement, cheap and well tolerated by participants. Additionally an interesting potential development of non-invasive neuromodulation interventions suggests the method is a viable technique for patients to use in their homes with remote monitoring [68]. However there is not currently a consensus on the optimal protocols and variability in effects across individuals have been widely reported. For translation to the clinic, systematic study into the effect of altering the amplitude and duration of the applied electrical current is essential. These parameters include; electrode montage when targeting a given area; size of the electrodes; magnitude of stimulation and duration of stimulation [69]. As with many therapeutic interventions key questions are; how can neurostimulation dose be determined?; how can treatment fidelity be ensured?; how can individual vari-

In tDCS the stimulation electrodes are typically two saline soaked sponge elec-

of interest and the reference electrode is positioned at another cortical region [70]. Early studies with tDCS used a very simple electrode montage, with two electrodes of the same size often with the assumption that the effect of the active electrode would be independent of the placement and size of the second, reference electrode. For motor cortex stimulation the typical electrode montage is to have the reference electrode placed over the contralateral orbit. It has been suggested that anodal stimulation protocols can be optimized by having the cathodal reference electrode as a larger size, thus rendering it functionally inert [71]. Another montage option has been the selection of an extracephalic reference electrode; typically the deltoid or buccinator muscles. Regardless of site used the montage of the two electrodes will inevitably impact on the regions where brain modulation will occur due to stimulation. Further the different forms of electrodes now available will also influence the applied stimulation as it is known that the electrode-skin interface has variable impedance that will be dependent on a number of factors that lead to variability in the delivered current. Modern

placed above the region

*DOI: http://dx.doi.org/10.5772/intechopen.93277*

ability be controlled when determining dose?

trodes; an anode and a cathode; that range from 25 to 35 cm2

**5.1 Electrode montage in tDCS**

*From Mechanisms to Analgesia: Towards the Use of Non-Invasive Neuromodulation for Pain… DOI: http://dx.doi.org/10.5772/intechopen.93277*

small; the tDCS protocols differ across studies; the patient groups are heterogeneous making meta-analysis challenging; and the study designs used inconsistent, with some studies favoring a cross-over design to a control group. For tDCS to become an established treatment intervention, large multi-centre randomized controlled trials with standardized protocols and patient cohorts are necessary.

Studies using VNS in patient groups report beneficial effects of this form of stimulation in patients with pain associated with inflammatory conditions, for instance rheumatoid arthritis or migraine. Indeed recent studies have provided strong support for the use of vagal nerve stimulation in arthritis patients [56]. The combination of anti-inflammatory effects of VNS [67] with the previously mentioned analgesic effects via the endogenous opioid system may explain the potential for this technique in these patient groups. In fibromyalgia, although the disease etiology is uncertain, patients are known to experience systemic inflammation and neuroinflammation, and so may be a patient group that particularly benefits from this intervention.
