Motor cortex stimulation for chronic neuropathic pain: results of a double-blind randomized study.

Motor cortex stimulation via surgically implanted electrodes has been used as an off-label treatment for chronic neuropathic pain, but its efficacy has not been fully established. We aimed to objectively study the efficacy of motor cortex stimulation and characterize potential predictors of response. In this randomized, double-blind, sham-controlled, single centre trial, we recruited 18 patients with chronic neuropathic pain who did not adequately respond to conventional treatment and had a numerical pain rating scale (NRS) score ≥6. Patients were initially assigned to receive 3 months of active ('on') or sham ('off') stimulation in a double-blind cross-over phase. This was followed by a 3-month single-blind phase, and 6 months of open-label follow-up. A meaningful response in our trial was defined as a ≥30% or 2-point reduction in NRS scores during active stimulation. Using Bayesian statistics, we found a 41.4% probability of response towards on versus off motor cortex stimulation. The probability of improvement during active stimulation (double-blind, single-blind and open-label phases) compared to baseline was 47.2-68.5%. Thirty nine per cent of the patients were considered long-term responders, 71.4% of whom had facial pain, phantom limb pain or complex regional pain syndrome. In contrast, 72.7% of non-responders had either post-stroke pain or pain associated with brachial plexus avulsion. Thirty-nine per cent of patients had a substantial postoperative analgesic effect after electrode insertion in the absence of stimulation. Individuals with diagnoses associated with a good postoperative outcome or those who developed an insertional effect had a near 100% probability of response to motor cortex stimulation. In summary, we found that ∼40% of patients responded to motor cortex stimulation, particularly those who developed an insertional effect or had specific clinical conditions that seemed to predict an appropriate postoperative response.

Quality of Life After Motor Cortex Stimulation: Clinical Results and Systematic Review of the Literature.

BACKGROUND: Motor cortex stimulation (MCS) is routinely used for the treatment of chronic neuropathic pain but its effect on quality of life remains uncertain. OBEJCTIVE: To systematically review the published literature on MCS and quality of life and report the effects of this therapy in a series of patients prospectively followed in our center. METHODS: The systematic literature review was conducted using the search words "motor cortex stimulation and pain and neurosurgery" and "motor cortex stimulation and pain and quality of life." Quality of life in our clinical trial was investigated in a series of 10 patients with chronic neuropathic pain prospectively followed for 12 mo after MCS. RESULTS: Two hundred eighteen nonreplicated articles were pooled for analysis. Of these, 6 described measures of quality of life in the pre- and postoperative period. In these studies, 64 patients with different clinical conditions associated with neuropathic pain were followed for 6 to 84 mo after MCS surgery. Improvement in quality of life ranged from 35% to 85%. In our clinical series, visual analog scale (VAS), SF-12 physical (PhysCS), and mental scores (MenCS) recorded 12 mo after MCS were improved by 60 ± 10% (P = .002), 50 ± 13% (P = .002), and 22 ± 6% (P = .01), respectively. No significant correlation was found between postoperative improvement in pain and either PhysCS (r = 0.18; P = .6) or MenCS (r = -0.24; P = .5). CONCLUSION: MCS improves quality of life in patients with chronic refractory neuropathic pain. Additional factors other than a simple analgesic effect may contribute to these results.

Epigenetics insights into chronic pain: DNA hypomethylation in fibromyalgia-a controlled pilot-study.

To evaluate changes in DNA methylation profiles in patients with fibromyalgia (FM) compared to matched healthy controls (HCs). All individuals underwent full clinical and neurophysiological assessment by cortical excitability (CE) parameters measured by transcranial magnetic stimulation. DNA from the peripheral blood of patients with FM (n = 24) and HC (n = 24) were assessed using the Illumina-HumanMethylation450 BeadChips. We identified 1610 differentially methylated positions (DMPs) in patients with FM displaying a nonrandom distribution in regions of the genome. Sixty-nine percent of DMP in FM were hypomethylated compared to HC. Differentially methylated positions were enriched in 5 genomic regions (1p34; 6p21; 10q26; 17q25; 19q13). The functional characterization of 960 genes related to DMPs revealed an enrichment for MAPK signaling pathway (n = 18 genes), regulation of actin cytoskeleton (n = 15 genes), and focal adhesion (n = 13 genes). A gene-gene interaction network enrichment analysis revealed the participation of DNA repair pathways, mitochondria-related processes, and synaptic signaling. Even though DNA was extracted from peripheral blood, this set of genes was enriched for disorders such as schizophrenia, mood disorders, bulimia, hyperphagia, and obesity. Remarkably, the hierarchical clusterization based on the methylation levels of the 1610 DMPs showed an association with neurophysiological measurements of CE in FM and HC. Fibromyalgia has a hypomethylation DNA pattern, which is enriched in genes implicated in stress response and DNA repair/free radical clearance. These changes occurred parallel to changes in CE parameters. New epigenetic insights into the pathophysiology of FM may provide the basis for the development of biomarkers of this disorder.