Pain
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Accumulating evidence points to significant cognitive disruption in individuals with Fibromyalgia Syndrome (FMS). This study was carried out in order to examine specific cognitive mechanisms involved in this disruption. Standardized experimental paradigms were used to examine attentional function and working memory capacity in 30 women with FMS and 30 matched controls. ⋯ These findings point to disrupted working memory as a specific mechanism that is disrupted in this population. The results of this study suggest that pain in FMS may play an important role in cognitive disruption. It is likely that many factors, including disrupted cognition, play a role in the reduced quality of life reported by individuals with FMS.
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EphBs receptors and ephrinBs ligands are present in the adult brain and peripheral tissue and play a critical role in modulating multiple aspects of physiology and pathophysiology. Ours and other studies have demonstrated that spinal ephrinBs/EphBs signaling was involved in the modulation of nociceptive information and central sensitization. However, the role of ephrinBs/EphBs signaling in peripheral sensitization is poorly understood. ⋯ EphrinB1-Fc-induced hyperalgesia is accompanied with the NMDA receptor-mediated increase of expression in peripheral and spinal phosphorylated mitogen-activated protein kinases (phospho-MAPKs) including p-p38, pERK and pJNK, and also is prevented or reversed by the inhibition of peripheral and spinal MAPKs. Furthermore, in formalin inflammation pain model, pre-inhibition of EphBs receptors by the injection of EphB1-Fc reduces pain behavior, which is accompanied by the decreased expression of peripheral p-p38, pERK and pJNK. These data provide evidence that ephrinBs may act as a prominent contributor to peripheral sensitization, and demonstrate that activation of peripheral ephrinBs/EphBs system induces hyperalgesia through a MAPKs-mediated mechanism.
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The synaptic vesicle protein synapsin II is specifically expressed in synaptic terminals of primary afferent nociceptive neurons and regulates transmitter release in the spinal cord dorsal horn. Here, we assessed its role in nerve injury-evoked molecular and behavioral adaptations in models of peripheral neuropathic pain using mice genetically lacking synapsin II. Deficiency of synapsin II resulted in reduced mechanical and cold allodynia in two models of peripheral neuropathic pain. ⋯ In addition, the expression of the vesicular glutamate transporters, VGLUT1 and VGLUT2, was strongly reduced in synapsin II knockout mice in the spinal cord. Conversely, synapsin II knockout mice showed a stronger and longer-lasting increase of GABA in lamina II of the dorsal horn after nerve injury than wild type mice. These results suggest that synapsin II is involved in the regulation of glutamate and GABA release in the spinal cord after nerve injury, and that a imbalance between glutamatergic and GABAergic synaptic transmission contributes to the manifestation of neuropathic pain.
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The increasing complexity of randomized clinical trials and the practice of obtaining a wide variety of measurements from study participants have made the consideration of multiple endpoints a critically important issue in the design, analysis, and interpretation of clinical trials. Failure to consider important outcomes can limit the validity and utility of clinical trials; specifying multiple endpoints for the evaluation of treatment efficacy, however, can increase the rate of false positive conclusions about the efficacy of a treatment. ⋯ To decrease the probability of a Type I error (i.e., the likelihood of obtaining statistically significant results by chance) in pain clinical trials, the use of gatekeeping procedures and other methods that correct for multiple analyses is recommended when a single primary endpoint does not adequately reflect the overall benefits of treatment. We emphasize the importance of specifying in advance the outcomes and clinical decision rule that will serve as the basis for determining that a treatment is efficacious and the methods that will be used to control the overall Type I error rate.
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The objective of this study was to examine the influence of variations in contextual features of a physically demanding lifting task on the judgments of others' pain. Healthy undergraduates (n=98) were asked to estimate the pain experience of chronic pain patients who were filmed while lifting canisters at different distances from their body. Of interest was whether contextual information (i.e., lifting posture) contributed to pain estimates beyond the variance accounted for by pain behavior. ⋯ Results also indicated that observers' level of catastrophizing was associated with more accurate pain estimates. The results of a regression analysis further showed that observers' level of catastrophizing contributed to the prediction of the accuracy of pain estimates over and above the variance accounted for by the utilisation of contextual features. Discussion addresses the processes that might underlie the utilisation of contextual features of a pain-eliciting task when estimating others' pain.