Pain
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Observational Study
Development and Validation of a New Self-Report Measure of Pain Behaviors.
Pain behaviors that are maintained beyond the acute stage after injury can contribute to subsequent psychosocial and physical disability. Critical to the study of pain behaviors is the availability of psychometrically sound pain behavior measures. In this study we developed a self-report measure of pain behaviors, the Pain Behaviors Self Report (PaB-SR). ⋯ Scores on the PaB-SR were found to be measurement invariant with respect to clinical condition. PaB-SR scores, observer reports, and the videotaped protocol yielded distinct, but convergent views of pain behavior, supporting the validity of the new measure. The PaB-SR is expected to be of substantial utility to researchers wishing to explore the relationship between pain behaviors and constructs such as pain intensity, pain interference, and disability.
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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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Chronic muscle pain affects 20-50% of the population, is more common in women than men, and is associated with increased pain during physical activity and exercise. Muscle fatigue is common in people with chronic muscle pain, occurs in response to exercise, and is associated with release of fatigue metabolites. Fatigue metabolites can sensitize muscle nociceptors, which could enhance pain with exercise. ⋯ Finally, muscle insult with or without muscle fatigue results in minimal inflammatory changes in the muscle itself, and sex differences are not related to estradiol (ovariectomy) or changes in brainstem activity (pNR1). Thus, the current model mimics muscle fatigue-induced enhancement of pain observed in chronic muscle pain conditions in the human population. Interactions between fatigue and muscle insult may underlie the development of chronic widespread pain with an associated female predominance observed in human subjects.
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Neuronal plasticity in the pain-processing pathway is thought to be a mechanism underlying pain hypersensitivity and negative emotions occurring during a pain state. Recent evidence suggests that the activation of astrocytes in the anterior cingulate cortex (ACC) contributes to the development of negative emotions during pain hypersensitivity after peripheral inflammation. However, it is unknown whether these activated astrocytes contribute to neuronal plasticity in the ACC. ⋯ The long-term facilitation in the CFA-injected mice was inhibited by the astroglial toxin, the N-methyl-d-aspartate (NMDA) receptor antagonist and NMDA receptor glycine binding site antagonist. The increase of intracellular Ca(2+) concentration in astrocytes during HFS was higher in the CFA-injected mice than in the control mice and was inhibited by l-α-aminoadipate (l-α-AA). These results suggest that the activation of astrocytes in the ACC plays a crucial role in the development of negative emotions and LTP during pain hypersensitivity after peripheral inflammation.
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Subsequent to peripheral nerve compression and irritation, pathophysiological processes take place within nervous and immune systems. Here, we utilized a multimodal approach to comprehend peripheral and central soft tissue changes as well as alterations occurring in systemic analytes following unilateral chronic constriction injury (CCI) of the sciatic nerve in rodents. Using magnetic resonance imaging and [18F]-2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography, we demonstrated robust structural abnormalities and enhanced FDG uptake within the injured nerve and surrounding muscle, respectively. ⋯ Area under the receiver operating curve (ROC) calculations of analyte levels, imaging, and behavioral end points ranged from 0.786 to 1, where behavioral and peripheral imaging end points (eg, FDG uptake in muscle) were observed to have the highest discriminatory capabilities (maximum area under ROC = 1) between nerve injury and sham conditions. Lastly, performance of correlation analysis involving all analyte, behavioral, and imaging data provided an understanding of the overall association amongst these end points, and importantly, a distinction in correlation patterns was observed between CCI and sham conditions. These findings demonstrate the multidimensional pathophysiology of sciatic nerve injury and how a combined analyte, behavioral, and imaging assessment can be implemented to probe this complexity.