Pain
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A functional allele of the mouse catechol-O-methyltransferase (Comt) gene is defined by the insertion of a B2 short interspersed repeat element in its 3'-untranslated region (UTR). This allele has been associated with a number of phenotypes, such as pain and anxiety. In comparison with mice carrying the ancestral allele (Comt+), Comt B2i mice show higher Comt mRNA and enzymatic activity levels. ⋯ Cell transfection with each miRNA downregulated the expression of the ancestral transcript and COMT enzymatic activity. Our in vivo experiments showed that mmu-miR-667-3p is strongly correlated with decreasing amounts of Comt mRNA in the brain, and lentiviral injections of mmu-miR-3470a, mmu-miR-3470b, and mmu-miR-667 increase hypersensitivity in the mouse formalin model, consistent with reduced COMT activity. In summary, our data demonstrate that the Comt+ transcript contains regulatory miRNA signals in its 3'-untranslated region leading to mRNA degradation; these signals, however, are absent in the shorter transcript, resulting in higher mRNA expression and activity levels.
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The objectives of this study were to explore the existence of subgroups in a cohort with chronic low back pain (n = 294) based on the results of multimodal sensory testing and profile subgroups on demographic, psychological, lifestyle, and general health factors. Bedside (2-point discrimination, brush, vibration and pinprick perception, temporal summation on repeated monofilament stimulation) and laboratory (mechanical detection threshold, pressure, heat and cold pain thresholds, conditioned pain modulation) sensory testing were examined at wrist and lumbar sites. Data were entered into principal component analysis, and 5 component scores were entered into latent class analysis. ⋯ Low back pain, therefore, does not appear to be homogeneous. Pain mechanisms relating to presentations of each subgroup were postulated. Future research may investigate prognoses and interventions tailored towards these subgroups.
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Overactivity is a frequently used term in chronic pain literature. It refers to the phenomenon whereby individuals engage in activity in a way that significantly exacerbates pain, resulting in periods of incapacity. Overactivity, as a construct, has been derived solely from patients' self-reports, raising concerns about the legitimacy of the construct. ⋯ Over the 5-day period, participants wore an activity monitor and recorded their pain intensity 6 times a day using a handheld computer. Associations were found between (1) high levels of pain and both high overactivity and high avoidance, (2) high levels of overactivity and more variation in pain and objective activity across days, and (3) high levels of overactivity and the reoccurrence of prolonged activity engagement followed by significant pain increases observed in data sets. These results offer some preliminary support for the validity of overactivity as a legitimate construct in chronic pain.
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In this study, we investigated the role of the endocannabinoid system (ECS) in the emotional and cognitive alterations associated with osteoarthritis pain. The monosodium iodoacetate model was used to evaluate the affective and cognitive manifestations of osteoarthritis pain in type 1 (CB1R) and type 2 (CB2R) cannabinoid receptor knockout and wild-type mice and the ability of CB1R (ACEA) and CB2R (JWH133) selective agonists to improve these manifestations during a 3-week time period. The levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were measured in plasma and brain areas involved in the control of these manifestations. ⋯ In agreement, an increase of 2-AG plasmatic levels and an upregulation of CB1R and CB2R gene expression in peripheral blood lymphocytes were observed in patients with osteoarthritis compared with healthy subjects. Changes found in these biomarkers of the ECS correlated with pain, affective, and cognitive symptoms in these patients. The ECS plays a crucial role in osteoarthritis and represents an interesting pharmacological target and biomarker of this disease.
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Pain captures attention, displaces current concerns, and prioritises escape and repair. This attentional capture can be measured by its effects on general cognition. Studies on induced pain, naturally occurring acute pain, and chronic pain all demonstrate a detrimental effect on specific tasks of attention, especially those that involve working memory. ⋯ Furthermore, we also found an effect of pain intensity; performance was poorer in participants with higher intensity compared with that in those with lower intensity pain. We suggest that the effects of pain on attention found in the laboratory occur in more naturalistic settings. Pain is common in the general population, and such interruption may have important, as yet uninvestigated, consequences for tasks of everyday cognition that involve working memory, such as concentration, reasoning, motor planning, and prospective memory.