Given the complexity of pain management in rehabilitation settings, pharmaco-behavioral interventions can capitalize on the self-modulatory process to enhance the effects of a drug-based intervention.

IntroductionFibromyalgia (FM) is a common debilitating condition with limited therapeutic options. Medications have low efficacy and are often associated with adverse effects. Given that FM is associated with a defective endogenous pain control system and central sensitisation, combining interventions such as transcranial direct current stimulation (tDCS) and aerobic exercise (AE) to modulate pain-processing circuits may enhance pain control.Methods and analysisA prospective, randomised (1:1:1:1), placebo-controlled, double-blind, factorial clinical trial will test the hypothesis that optimised tDCS (16 anodal tDCS sessions combined with AE) can restore of the pain endogenous control system. Participants with FM (n=148) will undergo a conditioning exercise period and be randomly allocated to one of four groups: (1) active tDCS and AE, (2) sham tDCS and AE, (3) active tDCS and non-aerobic exercise (nAE) or (4) sham tDCS and nAE. Pain inhibitory activity will be assessed using conditioned pain modulation (CPM) and temporal slow pain summation (TSPS)—primary outcomes. Secondary outcomes will include the following assessments: Transcranial magnetic stimulation and electroencephalography as cortical markers of pain inhibitory control and thalamocortical circuits; secondary clinical outcomes on pain, FM, quality of life, sleep and depression. Finally, the relationship between the two main mechanistic targets in this study—CPM and TSPS—and changes in secondary clinical outcomes will be tested. The change in the primary efficacy endpoint, CPM and TSPS, from baseline to week 4 of stimulation will be tested with a mixed linear model and adjusted for important demographic variables.Ethics and disseminationThis study obeys the Declaration of Helsinki and was approved by the Institutional Review Board (IRB) of Partners Healthcare under the protocol number 2017P002524. Informed consent will be obtained from participants. Study findings will be reported in conferences and peer-reviewed journal publications.Trial registration number NCT03371225.

Spasticity is common after a stroke and has a negative impact on functional and quality-of-life measures. There is an unmet medical need to provide safe and effective treatment using non-pharmacological approaches. Trans-spinal direct current stimulation (tsDCS) is an emerging modality for non-invasive neuromodulation that induces reduction of spinal excitability leading to a decrease in spasticity. We describe current treatment options for spasticity, including a literature review about the use of tsDCS in patients with spasticity. We found four clinical studies that used tsDCS to treat spasticity for different neurological conditions including hereditary spastic paraplegia, upper extremity spasticity following stroke, multiple sclerosis, and incomplete chronic spinal cord injury. Spasticity was the primary outcome in three of the studies and a secondary outcome in the final study. The three studies that addressed spasticity as the primary outcome found that active tsDCS decreased spasticity compared to sham. These studies suggest that tsDCS can modulate spinal motor and sensory spinal pathways through the use of specific electrode montages and stimulation parameters. This therapy can improve motor functions and may represent a viable treatment option for spasticity.