Pain
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This article is the first to present the Graphical Index of Pain (GRIP), a new user-friendly web-based method for high-throughput screening of pain. The long-term goal of the method is to improve global standardization of pain measurements. GRIP consists of a hierarchical body map with 10 first-tier body regions, and a second tier with multiple pain loci (167 among men, 168 among women), which provides detailed information about pain location and distribution. ⋯ Pain intensity at first-tier regions and pain location and distribution at second-tier regions are in this article presented by sex-stratified customized heat maps showing large sex difference. Mean time to mark the first- and second-tier regions was 74 seconds. In conclusion, GRIP allows for high-resolution assessment and presentation of pain location and distribution with minimal use of time.
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In clinical trials of treatments for chronic pain, the percentage of participants who withdraw early can be as high as 50%. Major reasons for early withdrawal in these studies include perceived lack of efficacy and adverse events. Commonly used strategies for accommodating missing data include last observation carried forward, baseline observation carried forward, and more principled methods such as mixed-model repeated-measures and multiple imputation. ⋯ These assumptions can depend, for example, on the stated reasons for dropout. We illustrate these methods using data from 4 clinical trials of pregabalin for the treatment of painful diabetic peripheral neuropathy and postherpetic neuralgia. When planning chronic pain clinical trials, careful consideration of the trial objectives should determine the definition of the trial estimand, which in turn should inform methods used to accommodate missing data in the statistical analysis.
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Attentional biases are posited to play a key role in the development and maintenance of chronic pain in adults and youth. However, research to date has yielded mixed findings, and few studies have examined attentional biases in pediatric samples. This study used eye-gaze tracking to examine attentional biases to pain-related stimuli in a clinical sample of youth with chronic pain and pain-free controls. ⋯ Attentional control did not moderate attentional biases between or within groups. The results lend support to theoretical models positing the presence of attentional biases in youth with chronic pain. Further research is required to clarify the nature of attentional biases and their relationship to clinical outcomes.
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Nicotinamide riboside (NR) is a vitamin B3 precursor of NAD that blunts diabetic and chemotherapy-induced peripheral neuropathy in preclinical models. This study examined whether NR also blunts the loss of intraepidermal nerve fibers induced by paclitaxel, which is associated with peripheral neuropathy. The work was conducted in female rats with N-methyl-nitrosourea (MNU)-induced tumors of the mammary gland to increase its translational relevance, and to assess the interaction of NR with paclitaxel and NR's effect on tumor growth. ⋯ Once daily administration of NR did not seem to alter tumor growth or the percentage of Ki67-positive tumor cells in rats that were not treated with paclitaxel and followed for 3 months. These results further support the ability of NR to play a protective role after nerve injury. They also suggest that NR may not only alleviate peripheral neuropathy in patients receiving taxane chemotherapy, but also offer an added benefit by possibly enhancing its tumor-suppressing effects.
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Understanding the mechanisms that drive transition from acute to chronic pain is essential to identify new therapeutic targets. The importance of endogenous resolution pathways acting as a "brake" to prevent development of chronic pain has been largely ignored. We examined the role of interleukin-10 (IL-10) in resolution of neuropathic pain induced by cisplatin. ⋯ Cisplatin treatment also depolarized the resting membrane potential, and decreased action potential voltage threshold and rheobase, while increasing ongoing activity at -45 mV and the amplitude of depolarizing spontaneous fluctuations. In vitro addition of IL-10 (10 ng/mL) reversed the effect of cisplatin on SA and on the depolarizing spontaneous fluctuation amplitudes, but unexpectedly had little effect on the other electrophysiological parameters affected by cisplatin. Collectively, our findings challenge the prevailing concept that IL-10 resolves pain solely by dampening neuroinflammation and demonstrate in a model of chemotherapy-induced neuropathic pain that endogenous IL-10 prevents transition to chronic pain by binding to IL-10 receptors on sensory neurons to regulate their activity.