Motor cortex stimulation for chronic pain: systematic review and meta-analysis of the literature.

OBJECTIVE: To conduct a systematic review and meta-analysis to quantify the efficacy of invasive and noninvasive brain stimulation for the treatment of chronic pain. METHODS: MEDLINE and other databases were searched as data sources. Reference lists and conference abstracts were examined for further relevant articles. We included studies that evaluated the effects of invasive and noninvasive brain stimulation of motor cortex on chronic pain using the visual analogue scale. Eleven studies using noninvasive brain stimulation and 22 studies using invasive brain stimulation met our inclusion criteria. The results showed that weighted responder rate was 72.6% (95% CI, 67.7-77.4) for the invasive stimulation studies and 45.3% (95% CI, 39.2-51.4) for the noninvasive stimulation studies. This difference was significant. For the noninvasive stimulation studies, the random effects model revealed that the number of responders in the active group was significantly higher as compared with sham stimulation group (risk ratio of 2.64) (95% CI, 1.63-4.30). CONCLUSIONS: This meta-analysis shows that two different techniques of brain stimulation of motor cortex--invasive and noninvasive--can exert a significant effect on pain in patients with chronic pain. We discuss potential reasons that invasive brain stimulation showed a larger effect in this meta-analysis. Our findings encourage continuation of research in this area and highlight the need for well-designed clinical trials to define the role of brain stimulation in pain management.

Low and high frequency repetitive transcranial magnetic stimulation for the treatment of spasticity.

The development of non-invasive techniques of cortical stimulation, such as transcranial magnetic stimulation (TMS), has opened new potential avenues for the treatment of neuropsychiatric diseases. We hypothesized that an increase in the activity in the motor cortex by cortical stimulation would increase its inhibitory influence on spinal excitability through the corticospinal tract and, thus, reduce the hyperactivity of the gamma and alpha neurons, improving spasticity. Seventeen participants (eight males, nine females; mean age 9y 1mo [SD 3y 2mo]) with cerebral palsy and spastic quadriplegia were randomized to receive sham, active 1Hz, or active 5Hz repetitive TMS of the primary motor cortex. Stimulation was applied for 5 consecutive days (90% of motor threshold). The results showed that there was a significant reduction of spasticity after 5Hz, but not sham or 1Hz, stimulation as indexed by the degree of passive movement; however this was not evident when using the Ashworth scale, although a trend for improvement was seen for elbow movement. The safety evaluation showed that stimulation with either 1Hz or 5Hz did not result in any adverse events as compared with sham stimulation. Results of this trial provide initial evidence to support further trials exploring the use of cortical stimulation in the treatment of spasticity.

A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury.

Past evidence has shown that motor cortical stimulation with invasive and non-invasive brain stimulation is effective to relieve central pain. Here we aimed to study the effects of another, very safe technique of non-invasive brain stimulation--transcranial direct current stimulation (tDCS)--on pain control in patients with central pain due to traumatic spinal cord injury. Patients were randomized to receive sham or active motor tDCS (2mA, 20 min for 5 consecutive days). A blinded evaluator rated the pain using the visual analogue scale for pain, Clinician Global Impression and Patient Global Assessment. Safety was assessed with a neuropsychological battery and confounders with the evaluation of depression and anxiety changes. There was a significant pain improvement after active anodal stimulation of the motor cortex, but not after sham stimulation. These results were not confounded by depression or anxiety changes. Furthermore, cognitive performance was not significantly changed throughout the trial in both treatment groups. The results of our study suggest that this new approach of cortical stimulation can be effective to control pain in patients with spinal cord lesion. We discuss potential mechanisms for pain amelioration after tDCS, such as a secondary modulation of thalamic nuclei activity.

Transcranial direct current stimulation of the unaffected hemisphere in stroke patients.

Recovery of function after a stroke is determined by a balance of activity in the neural network involving both the affected and the unaffected brain hemispheres. Increased activity in the affected hemisphere can promote recovery, while excessive activity in the unaffected hemisphere may represent a maladaptive strategy. We therefore investigated whether reduction of the excitability in the unaffected hemisphere by cathodal transcranial direct current stimulation could result in motor performance improvement in stroke patients. We compared these results with excitability-enhancing anodal transcranial direct current stimulation of the affected hemisphere and sham transcranial direct current stimulation. Both cathodal stimulation of the unaffected hemisphere and anodal stimulation of the affected hemisphere (but not sham transcranial direct current stimulation) improved motor performance significantly. These results suggest that the appropriate modulation of bihemispheric brain structures can promote motor function recovery.