Pain
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Clinical Trial
Temporal stability of conditioned pain modulation in healthy women over four menstrual cycles at the follicular and luteal phases.
Conditioned pain modulation (CPM) is a phenomenon that may be tested with a dynamic quantitative sensory test that assesses the inhibitory aspect of this pain modulatory network. Although CPM has been adopted as a clinical assessment tool in recent years, the stability of the measure has not been determined over long time intervals. The question of stability over time is crucial to our understanding of pain processing, and critical for the use of this tool as a clinical test. ⋯ The intraclass correlation coefficient for the CPM effect was modest (0.39; CI = 0.23-0.59), suggesting that there is significant variation in CPM over long time intervals. CPM did not vary across phases in the menstrual cycle. Prior to the adoption of CPM as a clinical tool to predict individual risk and aid diagnosis, additional research is needed to establish the measurement properties of CPM paradigms and evaluate factors that influence CPM effects.
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Despite a high prevalence of pain and ongoing effort to understand and reduce pain, studies show that there remains a considerable unmet need for pain relief and management. In part, this may be due to patient's not adhering to treatment recommendations. ⋯ Randomized, controlled trials of brief communication skills training have shown improved outcomes in primary care settings for patients with fibromyalgia and acute pain. Thus, although treatment of chronic pain is challenging, good communication between health providers and patients can promote adherence and improve outcomes.
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Common cancers, including cancers of the breast, lung, and prostate, frequently metastasize to multiple bones where they can cause significant and life-altering pain. Similar to cancer itself, the factors that drive bone cancer pain evolve and change with disease progression. Once cancer cells have metastasized to bone, both the cancer cells and their associated stromal cells generate pain by releasing algogenic substances including protons, bradykinin, endothelins, prostaglandins, proteases, and tyrosine kinase activators. ⋯ Tumor growth in bone can also generate a neuropathic pain by directly injuring nerve fibers as well as inducing an active and highly pathological sprouting of both sensory and sympathetic nerve fibers that normally innervate the bone. This structural reorganization of sensory and sympathetic nerve fibers in the bone, combined with the cellular and neurochemical reorganization that occurs in the spinal cord and brain, appears to contribute to the peripheral and central sensitization that is common in advanced bone cancer pain. These mechanistic insights have begun to lead to advances in both how we understand and treat bone cancer pain.
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Treating bone cancer pain poses a major clinical challenge, and the mechanisms underlying bone cancer pain remain elusive. EphrinB-EphB receptor signaling may contribute to bone cancer pain through N-methyl-d-aspartate receptor neuronal mechanisms. Here, we report that ephrinB-EphB signaling may also act through a Toll-like receptor 4 (TLR4)-glial cell mechanism in the spinal cord. ⋯ Intrathecal administration of an exogenous EphB1 receptor activator, ephrinB2-Fc, increased the expression of TLR4 and the levels of IL-1β and TNF-α, activated astrocytes and microglial cells, and induced thermal hypersensitivity. These ephrinB2-Fc-induced alterations were suppressed by spinal knockdown of TLR4. This study suggests that TLR4 may be a potential target for preventing or reversing bone cancer pain and other similar painful processes mediated by ephrinB-EphB receptor signaling.