Pain
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Tendon injury produces intractable pain and disability in movement, but the medications for analgesia and restoring functional integrity of tendon are still limited. In this study, we report that proteinase-activated receptor 2 (PAR2) activation in dorsal root ganglion (DRG) neurons contributes to chronic pain and tendon histopathological changes produced by Achilles tendon partial transection injury (TTI). Tendon partial transection injury increases the expression of PAR2 protein in both somata of DRG neurons and their peripheral terminals within the injured Achilles tendon. ⋯ Vitamin B complex (VBC), containing thiamine (B1), pyridoxine (B6), and cyanocobalamin (B12), is effective to ameliorate TTI-induced pain, inhibit ectopic nerve sprouting, and accelerate tendon repair, through suppressing PAR2 activation. These findings reveal a critical role of PAR2 signaling in the development of chronic pain and histopathological alterations of injured tendon following Achilles tendon injury. This study suggests that the pharmaceuticals targeting PAR2, such as VBC, may be an effective approach for the treatment of tendon injury-induced pain and promoting tendon repair.
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Randomized Controlled Trial
Top-down attention does not modulate mechanical hypersensitivity consecutive to central sensitization: insights from an experimental analysis.
According to the neurocognitive model of attention to pain, when the attentional resources invested in a task unrelated to pain are high, limited cognitive resources can be directed toward the pain. This is supported by experimental studies showing that diverting people's attention away from acute pain leads to experiencing less pain. Theoretical work has suggested that this phenomenon may present a top-down modulatory mechanism for persistent pain as well. ⋯ To assess the development of secondary hypersensitivity, sensitivity to mechanical stimuli was measured 3 times: T0, for baseline and 20 (T1) and 40 (T2) minutes after the procedure. We did not observe any significant difference in the development of secondary hypersensitivity between the 2 groups, neither in terms of the intensity of mechanical sensitivity nor its spatial extent. Our results suggest that a top-down modulation through attention might not be sufficient to affect pain sensitization and the development of secondary hypersensitivity.
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Ecological momentary assessment (EMA) allows for the collection of participant-reported outcomes (PROs), including pain, in the normal environment at high resolution and with reduced recall bias. Ecological momentary assessment is an important component in studies of pain, providing detailed information about the frequency, intensity, and degree of interference of individuals' pain. However, there is no universally agreed on standard for summarizing pain measures from repeated PRO assessment using EMA into a single, clinically meaningful measure of pain. ⋯ However, linear mixed-effect modeling estimators that account for the nonlinear relationship between average and variability of pain scores perform better for quantifying the true average pain and reduce estimation error by up to 50%, with larger improvements for individuals with more variable pain scores. We also show that binarizing pain scores (eg, <3 and ≥3) can lead to a substantial loss of statistical power (40%-50%). Thus, when examining pain outcomes using EMA, the use of linear mixed models using the entire scale (0-10) is superior to splitting the outcomes into 2 groups (<3 and ≥3) providing greater statistical power and sensitivity.
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Approximately 10% to 20% of individuals with previous SARS-CoV-2 infection may develop long-COVID syndrome, characterized by various physical and mental health issues, including pain. Previous studies suggested an association between small fibre neuropathy and pain in long-COVID cases. In this case-control study, our aim was to identify small fibre neuropathy in patients experiencing painful long-COVID syndrome. ⋯ This case-control study showed that approximately 50% of patients experiencing painful long-COVID syndrome had small fibre neuropathy. However, in our patient cohort, this specific post-COVID-19 complication was unrelated to demographic and COVID-19 clinical variables. Approximately half of our sample of patients with painful long-COVID symptoms met diagnostic criteria for small fibre neuropathy.