Pain
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Several different reporting biases cited in scientific literature have raised concerns about the overestimation of effects and the subsequent potential impact on the practice of evidence-based medicine and human health. Up to 7% to 8% of the population experiences neuropathic pain (NP), and established treatment guidelines are based predominantly on published clinical trial results. Therefore, we examined published randomized controlled trials (RCTs) of first-line drugs for NP and assessed the relative proportions with statistically significant (ie, positive) and nonsignificant (ie, negative) results and their rates of citation. ⋯ The time to publication, journal impact factor, and conflict of interest did not differ statistically between positive and negative studies. Our observations that negative and positive RCTs were published in journals with similar impact at comparable time-lags after study completion are encouraging. However, the citation bias for positive studies could affect the validity and generalization of conclusions in literature and potentially influence clinical practice.
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Group I metabotropic glutamate receptors (group I mGluRs) have been implicated in several central nervous system diseases including chronic pain. It is known that activation of group I mGluRs results in the production of inositol triphosphate (IP3) and diacylglycerol that leads to activation of extracellular signal-regulated kinases (ERKs) and an increase in neuronal excitability, but how group I mGluRs mediate this process remains unclear. We previously reported that Orai1 is responsible for store-operated calcium entry and plays a key role in central sensitization. ⋯ Dihydroxyphenylglycine-induced activation of ERKs and modulation of neuronal excitability are abolished in cultured Orai1-deficient neurons. Moreover, DHPG-induced nociceptive behavior is markedly reduced in Orai1-deficient mice. Our findings reveal previously unknown functional coupling between Orai1 and group I mGluRs and shed light on the mechanism underlying group I mGluRs-mediated neuronal plasticity.
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Yoga is frequently used for back pain relief. However, the evidence was judged to be of only low to moderate certainty. To assess the efficacy and safety of yoga in patients with low back pain, a meta-analysis was performed. ⋯ Compared with passive control, yoga was associated with short-term improvements in pain intensity (15 RCTs; mean difference [MD] = -0.74 points on a numeric rating scale; 95% confidence interval [CI] = -1.04 to -0.44; standardized mean difference [SMD] = -0.37 95% CI = -0.52 to -0.22), pain-related disability (15 RCTs; MD = -2.28; 95% CI = -3.30 to -1.26; SMD = -0.38 95% CI = -0.55 to -0.21), mental health (7 RCTs; MD = 1.70; 95% CI = 0.20-3.20; SMD = 0.17 95% CI = 0.02-0.32), and physical functioning (9 RCTs; MD = 2.80; 95% CI = 1.00-4.70; SMD = 0.28 95% CI = 0.10-0.47). Except for mental health, all effects were sustained long-term. Compared with an active comparator, yoga was not associated with any significant differences in short-term or long-term outcomes.
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Poststroke pain (PSP) is a heterogeneous term encompassing both central neuropathic (ie, central poststroke pain [CPSP]) and nonneuropathic poststroke pain (CNNP) syndromes. Central poststroke pain is classically related to damage in the lateral brainstem, posterior thalamus, and parietoinsular areas, whereas the role of white matter connecting these structures is frequently ignored. In addition, the relationship between stroke topography and CNNP is not completely understood. ⋯ Our exploratory analysis showed that, besides known thalamic and parietoinsular areas, significant voxels carrying a high risk for CPSP were located in the white matter encompassing thalamoinsular connections (one-tailed threshold Z > 3.96, corrected P value <0.05, odds ratio = 39.7). These results show that the interruption of thalamocortical white matter connections is an important component of CPSP, which is in contrast with findings from nonneuropathic PSP and from strokes without pain. These data can aid in the selection of patients at risk to develop CPSP who could be candidates to pre-emptive or therapeutic interventions.
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Clinical evidence indicates dorsal root ganglion (DRG) stimulation effectively reduces pain without the need to evoke paresthesia. This paresthesia-free anesthesia by DRG stimulation can be promising to treat pain from the viscera, where paresthesia usually cannot be produced. Here, we explored the mechanisms and parameters for DRG stimulation using an ex vivo preparation with mouse distal colon and rectum (colorectum), pelvic nerve, L6 DRG, and dorsal root in continuity. ⋯ Midrange frequencies (50-500 Hz) are more efficient at blocking transmission than lower or higher frequencies. In addition, DRG stimulation at 50 and 100 Hz significantly attenuates in vivo visceromotor responses to noxious colorectal balloon distension. This reversible conduction block in C-type and Aδ-type afferents by subkilohertz DRG stimulation likely underlies the paresthesia-free anesthesia by DRG stimulation, thereby offering a promising new approach for managing chronic visceral pain.