Pain
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Randomized Controlled Trial Multicenter Study
How do changes in pain severity levels correspond to changes in health status and function in patients with painful diabetic peripheral neuropathy?
The current analysis compares changes in pain with changes in function and health status in individuals with painful diabetic peripheral neuropathy (DPN). The post hoc analysis is based on a 12week, multinational, placebo-controlled trial of pregabalin in which 401 patients were randomized to treatment. Study measures included the Brief Pain Inventory short-form (BPI-sf), EQ-5D and other patient-reported outcomes. ⋯ Similarly, a reduction in the NRS of 30% and 50% corresponded to a 3-point and a 5-point improvement in the PII, respectively. Changes in pain were also associated with changes in health status. Results suggest that patients whose pain is not reduced to a mild level of severity can still experience clinically important changes in function and health status.
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There has been an increase in the number of chronic pain clinical trials in which the treatments being evaluated did not differ significantly from placebo in the primary efficacy analyses despite previous research suggesting that efficacy could be expected. These findings could reflect a true lack of efficacy or methodological and other aspects of these trials that compromise the demonstration of efficacy. ⋯ We present recommendations for the major components of confirmatory chronic pain clinical trials, including participant selection, trial phases and duration, treatment groups and dosing regimens, and types of trials. Increased attention to and research on the methodological aspects of confirmatory chronic pain clinical trials has the potential to enhance their assay sensitivity and ultimately provide more meaningful evaluations of treatments for chronic pain.
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Serine proteases and protease-activated receptor 2-dependent allodynia: a novel cancer pain pathway.
Mediators involved in the generation of pain in patients with cancer are poorly understood. Using a combined molecular, pharmacologic, behavioral, and genetic approach, we have identified a novel mechanism of cancer-dependent allodynia induced by protease-activated receptor 2 (PAR2). Here we show that human head and neck carcinoma cells have increased levels of proteolytic activity compared to normal human cell controls. ⋯ In addition, non-contact co-culture of trigeminal ganglion neurons with human head and neck carcinoma cells increased the proportion of neurons that exhibited PAR2-immunoreactivity. Our results point to a direct role for serine proteases and their receptor in the pathogenesis of cancer pain. This previously unrecognized cancer pain pathway has important therapeutic implications wherein serine protease inhibitors and PAR2 antagonists may be useful for the treatment of cancer pain.
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Due to the cross-sectional nature of previous studies, whether mechanical factors predict the onset of Chronic oro-facial pain remains unclear. Aims of the current study were to test the hypotheses that self-reported mechanical factors would predict onset of Chronic oro-facial pain and that any observed relationship would be independent of the confounding effects of psychosocial factors and reporting of other unexplained symptoms. About 1735 subjects who had completed a baseline questionnaire were assessed at 2year follow-up for the presence of Chronic oro-facial pain, psychosocial factors (anxiety and depression, illness behaviour, life stressors and reporting of somatic symptoms), mechanical dysfunction (facial trauma, grinding, phantom bite and missing teeth) and reporting of other unexplained symptoms (chronic widespread pain, irritable bowel syndrome and chronic fatigue). ⋯ I. 2.2-7.4) and age (RR 0.2, 95% CI 0.1-0.7). The findings from this prospective study support the hypothesis that psychosocial factors are markers for onset of Chronic oro-facial pain. The efficacy of early psychological management of Chronic oro-facial pain to address these factors should be a priority for future investigations.