Pain
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Pain is an alarm mechanism to prevent body damage in response to noxious stimuli. The nerve growth factor (NGF)/TrkA axis plays an essential role as pain mediator, and several clinical trials using antibodies against NGF have yielded promising results, but side effects have precluded their clinical approval. A better understanding of the mechanism of NGF/TrkA-mediated nociception is needed. ⋯ Simultaneous deletion of brain-derived neurotrophic factor (BDNF) reversed the effects of ARMS/Kidins220 knock down alone. Mechanistically, ARMS/Kidins220 levels are reduced in vitro and in vivo in response to capsaicin through calpains, and this reduction leads to enhanced regulated BDNF secretion from dorsal root ganglion. Altogether, these data indicate that ARMS/Kidins220 protein levels have a role as a pain modulator in the NGF/TrkA axis regulating BDNF secretion.
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Complex regional pain syndrome (CRPS) clinical trials have historically captured a diverse range of outcomes. A minimum set of CRPS patient-reported outcomes has been agreed for inclusion in a future CRPS international clinical research registry and data bank. This study aimed to identify a complementary set of core clinical outcomes. ⋯ Final outcomes recommended for inclusion in the core clinical set were record of medications, presence of posttraumatic stress disorder, extent of allodynia, and skin temperature difference between limbs. Study findings provide robust recommendations for core clinical outcome data fields in the future CPRS international clinical research registry. Alongside patient-reported outcomes, these data will enable a better understanding of CRPS.
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The potential consequences of the number of chronic pain sites (referred to multisite chronic pain) on the risk of cardiovascular diseases (CVDs) remain unclear. We attempted to investigate the causality of multisite chronic pain with CVDs and its possible causal mediators. Using summary genome-wide association statistics, two-sample Mendelian randomization (MR) analyses were performed to assess whether multisite chronic pain has a causal effect on the 3 CVDs including coronary artery disease, atrial fibrillation, and stroke. ⋯ We also found positive causal effects of multisite chronic pain on BMI, smoking, and depression and causal effects of BMI, smoking, and depression on coronary artery disease. In multivariable MR analyses, the excess risk of coronary artery disease was attenuated after adjusting for BMI (OR 1.43, 95% CI 1.05-1.93), smoking (OR 1.49, 95% CI 1.11-2.00), depression (OR 1.44, 95% CI 1.03-2.01), and 3 risk factors combined (OR 1.34, 95% CI 0.88-2.05). Our findings demonstrated that multisite chronic pain led to higher risk of coronary artery disease, which is partly mediated through BMI, smoking, and depression.
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Despite a preponderance of pain-related attentional bias research, little is known about how these biases arise and change over time. We tested whether the degree of attentional bias malleability , that is, ability to acquire and relinquish patterns of selective attention towards pain information, predicts daily pain interference. Individuals with chronic pain (N = 66) completed a novel attentional bias malleability procedure based on a modified dot-probe paradigm. ⋯ Greater attentional bias (F 1,391 = 3.97, P = 0.047), greater readiness to acquire an attentional bias (F 1,389 = 4.92, P = 0.027), and less readiness to lose an acquired attentional bias toward pain (F 1,354 = 5.18, P = 0.024) all predicted less pain interference. There was also an interaction between pain severity and overall attentional bias malleability (F 1,62 = 5.48, P = 0.023), such that as pain severity increased, those who showed greater attentional bias malleability showed less corresponding increase in their pain interference than those who showed less attentional bias malleability. This study adds new thinking to the dynamic nature of attentional bias and how such biases might arise and influence pain outcomes.
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Primary provoked vestibulodynia (PVD) is marked by the onset of symptoms at first provoking vulvar contact, whereas secondary PVD refers to symptom onset after some period of painless vulvar contact. Different pathophysiological processes are believed to be involved in the development and maintenance of primary PVD and secondary PVD. The primary aim of this study was to test the hypotheses that the resting state functional connectivity of the brain and brain stem regions differs between these subtypes. ⋯ Direct statistical comparisons by onset type indicated that women with secondary PVD have increased dorsal attention-somatomotor network connectivity, whereas women with primary PVD predominantly show increased intrinsic resting state connectivity within the brain stem and the default mode network. Furthermore, compared with women with primary PVD, those with secondary PVD reported greater incidence of early life sexual abuse, greater pain catastrophizing, greater 24-hour symptom unpleasantness, and less sexual satisfaction. The findings suggest that women with secondary PVD show greater evidence for central amplification of sensory signals, whereas women with primary PVD have alterations in brain stem circuitry responsible for the processing and modulation of ascending and descending peripheral signals.