Pain
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Chronic central neuropathic pain after central nervous system injuries remains refractory to therapeutic interventions. A novel approach would be to target key intracellular signaling proteins that are known to contribute to continued activation by phosphorylation of kinases, transcription factors, and/or receptors that contribute to changes in membrane excitability. We demonstrate that one signaling kinase, calcium/calmodulin-dependent kinase II (CaMKII), is critical in maintaining aberrant dorsal horn neuron hyperexcitability in the neuropathic pain condition after spinal cord injury (SCI). ⋯ To demonstrate causality, treatment of SCI rats with KN-93, which prevents CaMKII activation, significantly attenuated at-level mechanical allodynia and aberrant wide dynamic range neuronal activity evoked by brush, pressure, and pinch stimuli and a graded series of von Frey stimuli, respectively. Persistent CaMKII activation contributes to chronic central neuropathic pain by mechanisms that involve maintained hyperexcitability of wide dynamic range dorsal horn neurons. Furthermore, targeting key signaling proteins is a novel, useful therapeutic strategy for treating chronic central neuropathic pain.
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Diabetes comorbidities include disabling peripheral neuropathy (DPN) and an increased risk of developing cancer. Antimitotic drugs, such as paclitaxel, are well known to facilitate the occurrence of peripheral neuropathy. Practitioners frequently observe the development or co-occurrence of enhanced DPN, especially cold sensitivity, in diabetic patients during chemotherapy. ⋯ Moreover, mRNA levels of glutathione peroxidase 4 and glutathione-S-reductase were significantly lower in diabetic groups treated with paclitaxel. Finally, TRPA1 gene expression was enhanced by 45% in diabetic rats. Paclitaxel potentiation of cold hyperalgesia in diabetes may result from the combination of increased mitochondrial ROS production and poor radical detoxification induced by paclitaxel treatment and diabetes-related overexpression of TRPA1.
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Randomized Controlled Trial
Is there a potential role for attention bias modification in pain patients? Results of 2 randomised, controlled trials.
Potential applications of attention bias modification (ABM) for acute and chronic pain patients are investigated. In study 1, 54 acute back pain patients (46 of whom completed the study) were recruited at their initial physiotherapy session and randomised to receive 1 session of ABM or placebo. Patients were followed up 3 months later. ⋯ Although the results of these studies show that there is potential in the application of ABM to pain conditions, the mechanisms of treatment could not be established. Neither group showed an initial bias towards the word stimuli or a training effect, and only in the acute pain group were changes in biases related to outcome. Nonetheless, the fact that 2 independent samples showed a positive effect of ABM on clinical outcomes suggests that ABM is worthy of future study as an intervention for pain patients.
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This study examined the association of pain with subsequent disability retirement due to all causes as well as musculoskeletal diseases, mental disorders, and a heterogeneous group of other diseases and to study whether pain has an effect of its own after taking into account long-standing illness, physician-diagnosed diseases, working conditions, and occupational class, which are the key factors affecting disability retirement. The data consisted of the Helsinki Health Study baseline survey linked to national pension register data (n=6258). Mean follow-up time was 8.1 years. ⋯ Associations for acute pain were also found, but they were clearly weaker than those of chronic pain. Chronic pain contributes to disability retirement. Prevention and effective treatment of chronic pain may help prevent early retirement due to disability.
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The fear-avoidance model postulates that in chronic low back pain (CLBP) a fear of movement is acquired in the acute phase, which leads to subsequent avoidance of physical activity and contributes to the pain syndrome's becoming chronic. In the present event-related functional magnetic resonance imaging (fMRI) study of the neural correlates of the fear of movement, 60 women (30 CLBP patients, 15 healthy controls, and 15 women with spider phobia; mean age 46.8±9.8 years) participated. The CLBP patients were divided into a high and low fear-avoidant group on the basis of the Tampa Scale of Kinesiophobia. ⋯ The random-effects analysis showed no differences between high and low fear-avoidant CLBP patients or high fear-avoidant CLBP patients and controls. Normal fear-related activations were present in the high fear-avoidant CLBP patients for the generally fear-inducing pictures, demonstrating the validity of the stimulation paradigm and a generally unimpaired fear processing of the high fear-avoidant CLBP patients. Our findings do not support the fear component of the fear avoidance model.