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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To identify endogenous factors involved in herpetic pain, we performed genome-wide microarray analysis of the spinal cord of mice that suffered from herpetic allodynia induced by inoculation with herpes simplex virus type 1, which revealed marked induction of galectin-3, a β-galactoside-binding lectin. Therefore, we investigated the role of galectin-3 in herpetic allodynia. The expression levels of galectin-3 mRNA and protein were increased with a temporal pattern similar to that of herpetic allodynia. ⋯ Intrathecal injection of galectin-3 produced mechanical allodynia in naive mice, and intrathecal injections of anti-galectin-3 antibodies significantly reduced herpetic allodynia. The present results suggest that galectin-3 in infiltrating macrophages and/or resident microglia in the spinal dorsal horn contributes to herpetic allodynia. Galectin-3 may be a new therapeutic target for the treatment of herpes zoster-associated 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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Multicenter Study
Which domains should be included in a cancer pain classification system? Analyses of longitudinal data.
The overall aim of the present study was to further develop an evidence-based platform for the content of an international cancer pain classification system. Data from a multicentre, observational longitudinal study of cancer patients were analysed. Analyses were carried out in 2 samples: (A) Cross-sectional data of patients on opioids at inclusion, and (B) patients just admitted to palliative care. ⋯ Identified domains explained 16% to 24% of the variability of the pain outcome. Initial pain intensity emerged as the strongest predictor of pain outcome after 2 weeks, and incident pain was confirmed to be a relevant domain. The regression models explained only a minor part of the variability of pain outcomes.