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Pain is a private experience, whose assessment relies on subjective self-reporting. Inaccurate communication renders pain evaluation unreliable in individuals with alteration of consciousness, lack of verbal interaction, cognitive dysfunction or simple malingering, hence the importance of developing reliable objective assessment tools.
Learn More >Scarce data are available on the use of vedolizumab in children with inflammatory bowel disease (IBD). We aimed to evaluate the safety, effectiveness, and dosing of vedolizumab to induce remission of IBD.
Learn More >Catechol-O-methyltransferase (COMT) has been shown to influence clinical pain, descending modulation, and exercise-induced symptom worsening. COMT regulates nociceptive processing and inflammation, key pathophysiological features of Chronic Fatigue Syndrome and Fibromyalgia (CFS/FM). We aimed to determine the interactions between genetic and epigenetic mechanisms regulating COMT and its influence on inflammatory markers and symptoms in patients with CFS/FM.
Learn More >Monthly headache frequency directly correlates with personal/societal burden and impacts severity and preventive treatment decisions. This post hoc analysis identified shifts from higher to lower frequency headache categories over 6 months in patients with migraine participating in the PROMISE clinical trials receiving two eptinezumab doses.
Learn More >Typically, athletes alter movement mechanics in the presence of back pain, but the effect of these changes on lower extremity injury risk is not well understood. This study aimed to compare the effect of fatigue on electromechanical response times during a choice reaction task in basketball players with and without persistent low back pain. Twenty-four male basketball players participated. Total reaction time (TRT), premotor time (PMT), and electromechanical delay (EMD data were recorded before and after fatigue. The chronic low back pain (CLBP) group had significantly longer EMD in Med gastrocnemius (p = 0.001) and Tibialis anterior (p = 0.001), and shorter EMD in Vastus Lateralis (p = 0.001), Vastus Medialis Oblique (p = 0.003), and Semitendinosus (p = 0.025) muscles after fatigue. PMT in the CLBP group had longer than the Non-CLBP in Vastus Lateralis (p = 0.010), Vastus Medialis Oblique (p = 0.017), Semitendinosus (p = 0.002). Also, TRT was longer in knee flexion (p = 0.001) and ankle plantarflexion (p = 0.001) muscle groups. The different effects of fatigue on electromechanical response times of the knee and ankle in people with CLBP may represent the effect of an axial injury on lower extremity injury risk factors in situations of higher cognitive load, similar to competitive play.
Learn More >To compare demographic and pain characteristics of older (≥ 65) vs younger (< 65) chronic non-cancer pain patients referred to a community pain clinic in the Greater Toronto Area (GTA), Ontario, Canada.
Learn More >The transmembrane protein TMEM206 was recently identified as the molecular basis of the extracellular proton-activated Cl channel (PAC), which plays an essential role in neuronal death in ischemia-reperfusion. The PAC channel is activated by extracellular acid, but the proton-sensitive mechanism remains unclear, although different acid-sensitive pockets have been suggested based on the cryo-EM structure of the human PAC (hPAC) channel. In the present study, we firstly identified two acidic amino acid residues that removed the pH-dependent activation of the hPAC channel by neutralization all the conservative negative charged residues located in the extracellular domain of the hPAC channel and some positively charged residues at the hotspot combined with two-electrode voltage-clamp (TEVC) recording in the oocytes system. Double-mutant cycle analysis and double cysteine mutant of these two residues proved that these two residues cooperatively form a proton-sensitive site. In addition, we found that chloral hydrate activates the hPAC channel depending on the normal pH sensitivity of the hPAC channel. Furthermore, the PAC channel knock-out (KO) male mice (C57BL/6J) resist chloral hydrate-induced sedation and hypnosis. Our study provides a molecular basis for understanding the proton-dependent activation mechanism of the hPAC channel and a novel drug target of chloral hydrate.Proton-activated Cl channel (PAC) channels are widely distributed in the nervous system and play a vital pathophysiological role in ischemia and endosomal acidification. The main discovery of this paper is that we identified the proton activation mechanism of the human proton-activated chloride channel (hPAC). Intriguingly, we also found that anesthetic chloral hydrate can activate the hPAC channel in a pH-dependent manner. We found that the chloral hydrate activates the hPAC channel and needs the integrity of the pH-sensitive site. In addition, the PAC channel knock-out (KO) mice are resistant to chloral hydrate-induced anesthesia. The study on PAC channels' pH activation mechanism enables us to better understand PAC's biophysical mechanism and provides a novel target of chloral hydrate.
Learn More >The goal of the Edmonton Classification System for Cancer Pain (ECS-CP) is to create an international classification system for cancer pain. Previous studies reinforce the need for standardized training to ensure consistency across assessors. There is no universally accepted classification for neuropathic pain. Our primary objective was to describe the prevalence of ECS-CP features in a diverse sample of advanced cancer patients, using assessors with standardized training. The secondary objectives were to: (1) determine the prevalence of neuropathic pain using the Neuropathic Pain Special Interest Group (NeuPSIG) criteria and (2) examine the relationship between specific predictors: ECS-CP features, age, Palliative Performance Scale, Morphine Equivalent Daily Dose (MEDD), setting, and pain intensity; and neuropathic pain. A total of 1050 adult patients with advanced cancer were recruited from 11 Canadian sites. A clinician completed the ECS-CP and NeuPSIG criteria, and collected additional information including demographics and pain intensity (now). All assessors received standardized training. Of 1050 evaluable patients, 910 (87%) had cancer pain: nociceptive ( = 626; 68.8%); neuropathic ( = 227; 24.9%); incident ( = 329; 36.2%); psychological distress ( = 209; 23%); addictive behavior ( = 51; 5.6%); and normal cognition ( = 639; 70.2%). The frequencies of ECS-CP features and pain intensity scores varied across sites and settings, with more acute settings having higher frequencies of complex pain features. The overall frequency of neuropathic pain was 24.9%, ranging from 11% (hospices) to 34.2% (palliative outpatient clinic) across settings. Multivariate logistic regression analysis revealed that age <60 years, MEDD ≥19 mg, pain intensity ≥7/10, and incident pain were significant independent predictors of neuropathic pain ( < 0.05). The ECS-CP was able to detect salient pain features across settings. Furthermore, the frequencies of neuropathic pain utilizing the NeuPSIG criteria fits within the lower-end of literature estimates (13%-40%). Further research is warranted to validate the NeuPSIG criteria in cancer pain.
Learn More >Enhancing the therapeutic alliance has been associated with improved outcomes for patients with chronic low back pain (CLBP). Qualitatively trust has been described to be part of the therapeutic alliance, but it has not been measured quantitatively within the physical therapy literature.
Learn More >Preoperative sleep loss can amplify post-operative mechanical hyperalgesia. However, the underlying mechanisms are still largely unknown. In the current study, rats were randomly allocated to a control group and an acute sleep deprivation (ASD) group which experienced 6 h ASD before surgery. Then the variations in cerebral function and activity were investigated with multi-modal techniques, such as nuclear magnetic resonance, functional magnetic resonance imaging, c-Fos immunofluorescence, and electrophysiology. The results indicated that ASD induced hyperalgesia, and the metabolic kinetics were remarkably decreased in the striatum and midbrain. The functional connectivity (FC) between the nucleus accumbens (NAc, a subregion of the ventral striatum) and the ventrolateral periaqueductal gray (vLPAG) was significantly reduced, and the c-Fos expression in the NAc and the vLPAG was suppressed. Furthermore, the electrophysiological recordings demonstrated that both the neuronal activity in the NAc and the vLPAG, and the coherence of the NAc-vLPAG were suppressed in both resting and task states. This study showed that neuronal activity in the NAc and the vLPAG were weakened and the FC between the NAc and the vLPAG was also suppressed in rats with ASD-induced hyperalgesia. This study highlights the importance of preoperative sleep management for surgical patients.
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