Pain
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Chronic itch is clinically correlated with the development of mood disorders such as anxiety and depression. Nonetheless, whether this relevance exists in rodents is unknown, and evidence demonstrating chronic itch can affect mood is lacking. The aim of this study is to characterize the affective consequences of chronic itch, and explore potential mechanisms and interventional strategy. ⋯ Parameters of HPA functionality at the level of mRNA transcripts are altered in stress-related brain regions of AEW mice, implying an overdrive of central CRF system. Remarkably, chronic treatment of AEW mice with antalarmin, a CRFR1 antagonist, ameliorated both their mood impairment and stress axis dysfunction. This is the first evidence revealing mood impairment, HPA axis dysfunction, and potential therapeutic efficacy by CRFR1 antagonist in mice with chronic itch, thus providing a preclinical model to investigate the affective consequence of chronic itch and the underlying mechanisms.
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Electrophysiological characterisation of central sensitisation in canine spontaneous osteoarthritis.
In man, central sensitisation (CS) contributes to the pain of osteoarthritis (OA). Dogs with spontaneous OA may also exhibit CS. Electrophysiological reflex measurements are more objective than behavioural assessments and can be used to evaluate CS in preclinical and clinical studies. ⋯ Temporal summation demonstrated exaggerated C-fibre-mediated responses in both OA (P < 0.001) and OANSAID (P = 0.005) groups, compared with control animals. Conditioning stimulus application resulted in inhibition of test reflex responses in both OA and control animals (P < 0.001); control animals demonstrated greater inhibition compared with OA (P = 0.0499). These data provide evidence of neurophysiological changes consistent with CS in dogs with spontaneous OA and demonstrate that canine OA is associated with reduced DNIC.
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Review Meta Analysis
Neuropathic pain clinical trials: factors associated with decreases in estimated drug efficacy.
Multiple recent pharmacological clinical trials in neuropathic pain have failed to show beneficial effect of drugs with previously demonstrated efficacy, and estimates of drug efficacy seems to have decreased with accumulation of newer trials. However, this has not been systematically assessed. Here, we analyze time-dependent changes in estimated treatment effect size in pharmacological trials together with factors that may contribute to decreases in estimated effect size. ⋯ Several factors that changed over time, such as larger study size, longer study duration, and more studies reporting 50% or 30% pain reduction, correlated with the decrease in estimated drug effect sizes. This suggests that issues related to the design, outcomes, and reporting have contributed to changes in the estimation of treatment effects. These factors are important to consider in design and interpretation of individual study data and in systematic reviews and meta-analyses.
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Randomized Controlled Trial
Efficacy of adding interoceptive exposure to intensive interdisciplinary treatment for adolescents with chronic pain: a randomized controlled trial.
Fear of pain plays an important role in the maintenance of chronic pain. It may be reduced through exposure therapy. This 2-arm parallel samples randomized controlled trial aimed to investigate whether interoceptive exposure (IE) therapy enhances reductions in fear of pain (primary outcome), pain (pain intensity, pain-related disability, and school absence), and emotional characteristics (anxiety and catastrophizing) when implemented as an adjunctive treatment in the context of intensive interdisciplinary pain treatment for pediatric chronic pain patients. ⋯ There were no greater decreases in the IE group (P > 0.1). The exploratory analyses revealed that the patients with high fear of pain before treatment (P < 0.05, (Equation is included in full-text article.)> 0.03) and the patients with abdominal pain (P < 0.04, (Equation is included in full-text article.)> 0.25) showed greater decreases in their fear of pain (total and subscale score) in the IE group than in the RT group. In conclusion, the results suggest that IE is not particularly effective for all the pediatric chronic pain patients, but the patients with high fear of pain before treatment and with abdominal pain strongly benefit from this intervention.
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Randomized Controlled Trial
Aδ and not C fibers mediate thermal hyperalgesia to short laser stimuli after burn injury in man.
It remains unclear which nerve fibers are responsible for mediating hyperalgesia after skin injury. Here, we examined the role of Aδ and C fibers in inflammatory hyperalgesia after a first-degree burn injury. A CO2 laser delivered ultrafast short constant-temperature heat pulses to the upper part of the lower leg to stimulate selectively the relatively fast-conducting thinly myelinated Aδ and the slowly conducting unmyelinated C fibers. ⋯ No group differences in C-fiber-mediated sensations were observed. Our findings indicate that quickly adapting Aδ fibers but not quickly adapting C fibers are sensitized when activated by short and ultrafast heat stimuli after skin burn injury. Our results further show that this change occurs between 1 hour and 24 hours after injury and that it does not extend to the skin surrounding the injury.