Pain
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Randomized Controlled Trial
Transcranial direct current stimulation of three cortical targets is no more effective than placebo as treatment for fibromyalgia: a double-blind sham-controlled clinical trial.
Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) and the dorsolateral prefrontal cortex seem to improve pain and other symptoms of fibromyalgia (FM), although the evidence on the effectiveness of tDCS and the optimal stimulation target is not robust enough. Our main objective was to establish the optimal area of stimulation, comparing the 2 classical targets and a novel pain-related area, the operculo-insular cortex, in a sham-controlled trial. Using a double-blind design, we randomly assigned 130 women with FM to 4 treatment groups (M1, dorsolateral prefrontal cortex, operculo-insular cortex, and sham), each receiving fifteen 20-minute sessions of 2 mA anodal tDCS over the left hemisphere. ⋯ The linear mixed-model analysis of variances showed significant treatment effects across time for clinical pain and for fatigue, cognitive and sleep disturbances, and experimental pain, irrespective of the group. In mood, the 3 active tDCS groups showed a significantly larger improvement in anxiety and depression than sham. Our findings provide evidence of a placebo effect, support the use of tDCS for the treatment of affective symptoms, and challenge the effectiveness of tDCS as treatment of FM.
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We conducted a complier average causal effect (CACE) analyses for 2 pragmatic randomised controlled trials. We aimed to assess the effectiveness of telephone-based lifestyle weight loss interventions compared with usual care among compliers. Participants from 2 trials with low back pain (n = 160) and knee osteoarthritis (n = 120) with a body mass index ≥27 kg/m2 were included. ⋯ Complier average causal effect estimates showed potentially clinically meaningful effects, but with low certainty because of wide confidence intervals, for pain intensity (-1.4; 95% confidence interval, -3.1, 0.4) and small but also uncertain effects for disability (-2.1; 95% confidence interval, -8.6, 4.5) among compliers in the low back pain trial intervention compared with control but not in the knee osteoarthritis trial. Our findings showed that compliers of a telephone-based weight loss intervention in the low back pain trial generally had improved outcomes; however, there were inconsistent effects in compliers from the knee osteoarthritis trial. Complier average causal effect estimates were larger than intention-to-treat results but must be considered with caution.
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The pathophysiology of fibromyalgia syndrome (FMS) remains elusive, leading to a lack of objective diagnostic criteria and targeted treatment. We globally evaluated immune system changes in FMS by conducting multiparametric flow cytometry analyses of peripheral blood mononuclear cells and identified a natural killer (NK) cell decrease in patients with FMS. Circulating NK cells in FMS were exhausted yet activated, evidenced by lower surface expression of CD16, CD96, and CD226 and more CD107a and TIGIT. ⋯ Genetic and transcriptomic pathway analyses identified significant enrichment of cell activation pathways in FMS driven by NK cells. Skin biopsies showed increased expression of NK activation ligand, unique long 16-binding protein, on subepidermal nerves of patients FMS and the presence of NK cells near peripheral nerves. Collectively, our results suggest that chronic activation and redistribution of circulating NK cells to the peripheral nerves contribute to the immunopathology associated with FMS.
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Alpha oscillatory activity (8-13 Hz) is the dominant rhythm in the awake brain and is known to play an important role in pain states. Previous studies have identified alpha band slowing and increased power in the dynamic pain connectome (DPC) of people with chronic neuropathic pain. However, a link between alpha-band abnormalities and sex differences in brain organization in healthy individuals and those with chronic pain is not known. ⋯ In the neuropathic pain group, women exhibited lower PAF power in the subgenual anterior cingulate cortex and faster PAF in the ANP and SN than men. The within-sex analyses indicated that women had neuropathic pain-related increased PAF power in the ANP, SN, and default mode network, whereas men with neuropathic pain had increased PAF power restricted to the ANP. These findings highlight neuropathic pain-related and sex-specific abnormalities in alpha oscillations across the DPC that could underlie aberrant neuronal communication in nociceptive processing and modulation.
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Top-down processes allow the selection and prioritization of information by limiting attentional capture by distractors, and these mechanisms depend on task demands such as working memory (WM) load. However, bottom-up processes give salient stimuli a stronger neuronal representation and provoke attentional capture. The aim of this study was to examine the effect of salient nociceptive stimuli on WM while manipulating task demands. ⋯ Moreover, compared with control stimuli, nociceptive stimuli abolished the increase in contralateral delay activity amplitude for set size 4 vs set size 2 (P = 0.04). Consistent with these results, laser-evoked potential amplitude was not decreased when task demands were high (P = 0.5). These findings indicate that WM may shield cognition from nociceptive stimuli, but nociceptive stimuli disrupt WM and alter task performance when cognitive resources become insufficient to process all task-relevant information.