Pain
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Randomized Controlled Trial
Vaso-occlusive crisis pain intensity, frequency, and duration: which best correlates with health-related quality of life in adolescents and adults with sickle cell disease?
In a cross-sectional analysis of baseline data from a randomized clinical trial, we studied 198 adolescents and adults aged 15+ with sickle cell disease. Interest was in assessing the relative strengths of the relationship of vaso-occlusive crisis (VOC) pain domains of intensity, frequency, and duration, with health-related quality of life (HRQOL). Variation in psychosocial, physical function, and pain expression domains of HRQOL was partially explained by frequency, intensity, and duration of VOC pain, separately and together, over and above differences in age, sex, genotype, and organ system damage. ⋯ Vaso-occlusive crisis pain frequency explained the most variation, when simultaneously considering VOC intensity and duration, except for stiffness , where duration was most predictive. Yet VOC pain intensity, and even VOC duration, also contributed to variability in HRQOL. We recommend that for most purposes, because all 3 VOC pain domains contribute to variability in HRQOL, all 3 domains should be assessed and interventions should be targeted to improve all 3 domains to maximize HRQOL outcomes (Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02197845 ).
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The persistence of inflammatory and neuropathic pain is poorly understood. We investigated a novel therapeutic paradigm by targeting gene networks that sustain or reverse persistent pain states. Our prior observations found that Sp1-like transcription factors drive the expression of TRPV1, a pain receptor, that is blocked in vitro by mithramycin A (MTM), an inhibitor of Sp1-like factors. ⋯ Mithramycin-dependent changes in gene expression following oxaliplatin treatment were largely opposite to and rarely overlapped with changes in gene expression induced by oxaliplatin alone. Notably, RNAseq analysis revealed MTM rescue of oxaliplatin-induced dysregulation of mitochondrial electron transport chain genes that correlated with in vivo reversal of excess reactive oxygen species in DRG neurons. This finding suggests that the mechanism(s) driving persistent pain states such as CIPN are not fixed but are sustained by ongoing modifiable transcription-dependent processes.
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In the United States, a public-health crisis of opioid overuse has been observed, and in Europe, prescriptions of opioids are strongly increasing over time. The objective was to develop and validate a multivariable prognostic model to be used at the beginning of an opioid prescription episode, aiming to identify individual patients at high risk for long-term opioid use based on routinely collected data. Predictors including demographics, comorbid diseases, comedication, morphine dose at episode initiation, and prescription practice were collected. ⋯ Using a threshold of 10% predicted probability to identify patients at high risk, the overall accuracy of this risk prediction model was 81.6% (95% confidence interval 81.2% to 82.0%). Our study demonstrated that long-term opioid use can be predicted at the initiation of an opioid prescription episode, with satisfactory accuracy using data routinely collected at a large health insurance company. Traditional statistical methods resulted in higher discriminative ability and similarly good calibration as compared with machine learning approaches.
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Neuropathic pain is associated with substantial healthcare costs. However, cost-of-illness studies of small fiber neuropathy (SFN) are scarce. Our aim was to estimate the healthcare, patient and family, and productivity costs of patients with SFN in the Netherlands from a healthcare and societal perspective. ⋯ At the patient level, the average annual SFN healthcare and societal cost of SFN was €3614 (95% confidence interval [CI] €3171-€4072) and €17,871 (95% CI €14,395-€21,480). At the SFN population level, the average healthcare costs were €29.8 (CI €26.4-€34.2) million, and on a societal level, these were €147.7 (CI 120.5-176.3) million. Severe pain was associated with significant lower Qol and higher depression scores, higher healthcare, patient and family, and productivity costs ( P < 0.001).
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Nerve injury-induced aberrant changes in gene expression in spinal dorsal horn neurons are critical for the genesis of neuropathic pain. N6-methyladenine (m 6 A) modification of DNA represents an additional layer of gene regulation. Here, we report that peripheral nerve injury significantly decreased the level of m 6 A-specific DNA methyltransferase 1 ( N6amt1 ) in dorsal horn neurons. ⋯ Rescuing the decrease in N6amt1 reversed the loss of m 6 A at the promoter for inwardly rectifying potassium channel subfamily J member 16 ( Kcnj16 ), mitigating the nerve injury-induced upregulation of Kcnj16 expression in the dorsal horn and alleviating neuropathic pain hypersensitivities. Conversely, mimicking the downregulation of N6amt1 in naive mice erased DNA m 6 A at the Kcnj16 promoter, elevated Kcnj16 expression, and led to neuropathic pain-like behaviors. Therefore, decreased N6amt1 caused by NR2F6 is required for neuropathic pain, likely through its regulation of m 6 A-controlled KCNJ16 in dorsal horn neurons, suggesting that DNA m 6 A modification may be a potential new target for analgesic and treatment strategies.