Pain
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Few investigations examine patterns of opioid and nonopioid analgesic prescribing and concurrent pain intensity ratings before and after institution of safer prescribing programs such as the October 2013 Veterans Health Administration system-wide Opioid Safety Initiative (OSI) implementation. We conducted a quasi-experimental pre-post observational study of all older U. S. veterans (≥50 years old) with osteoarthritis of the knee or hip. ⋯ No changes in nonsteroidal anti-inflammatory drug prescribing were seen. A small rise in the percentage of those reporting pain but not mean pain intensity ratings continued over the study period with no changes associated with OSI. Changes in analgesic prescribing trends were not paralleled by changes in reported pain intensity for older veterans with osteoarthritis.
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The mechanisms responsible for the persistence of chemotherapy-induced peripheral neuropathy (CIPN) in a significant proportion of cancer survivors are still unknown. Our previous findings show that CD8 T cells are necessary for the resolution of paclitaxel-induced mechanical allodynia in male mice. In this study, we demonstrate that CD8 T cells are not only essential for resolving cisplatin-induced mechanical allodynia, but also to normalize spontaneous pain, numbness, and the reduction in intraepidermal nerve fiber density in male and female mice. ⋯ Moreover, adoptive transfer of cisplatin-educated CD8 T cells to Rag2 mice prevented CIPN development induced by either cisplatin or paclitaxel, indicating that the activity of the educated CD8 T is not cisplatin specific. In conclusion, resolution of CIPN requires in vivo education of CD8 T cells by exposure to cisplatin. Future studies should examine whether ex vivo CD8 T cell education could be applied as a therapeutic strategy for treating or preventing CIPN in patients.
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Diabetic neuropathy is an incapacitating complication in diabetic patients. The cellular and molecular mechanisms involved in this pathology are poorly understood. Previous studies have suggested that the loss of spinal GABAergic inhibition participate in painful diabetic neuropathy. ⋯ L-655,708 (15 nmol) increased tonic excitability of the primary afferents without affecting the phasic excitability produced by the primary afferent depolarization. α5GABAA receptors were immunolocalized in superficial laminae of the dorsal horn and L4 to L6 dorsal root ganglion. Streptozotocin increased mean fluorescence intensity and percentage of neurons expressing α5GABAA receptors in dorsal horn and L4 to L6 dorsal root ganglia in 10-week diabetic rats. Our results suggest that spinal α5GABAA receptors modulate the HR, play an antinociceptive and pronociceptive role in healthy and diabetic rats, respectively, and are tonically active in primary afferents.
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Accumulating evidence has shown that complicated brain systems are involved in the development and maintenance of chronic low back pain (cLBP), but the association between brain functional changes and clinical outcomes remains unclear. Here, we used resting-state functional magnetic resonance imaging (fMRI) and multivariate pattern analysis to identify abnormal functional connectivity (FC) between the default mode, sensorimotor, salience, and central executive brain networks in cLBP and tested whether abnormal FCs are related to pain and comorbid symptoms. Fifty cLBP patients and 44 matched healthy controls (HCs) underwent an fMRI scan, from which brain networks were identified by independent component analysis. ⋯ Finally, we found that resting-state FC could discriminate cLBP patients from HCs with 91% accuracy in the first cohort and 78% accuracy in the validation cohort. Our findings suggest that the medial prefrontal cortex/rostral anterior cingulate cortex may be an important hub for linking the default mode network with the other 3 networks in cLBP patients. Elucidating the altered FCs and their association with clinical outcomes will enhance our understanding of the pathophysiology of cLBP and may facilitate the development of pain management approaches.
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Trigeminal spinal subnucleus caudalis (Vc) neurons that project to the ventral posteromedial thalamic nucleus (VPM) and parabrachial nucleus (PBN) are critical for orofacial pain processing. We hypothesized that persistent trigeminal nerve injury differentially alters the proportion of Vc neurons that project to VPM and PBN in a modality-specific manner. Neuroanatomical approaches were used to quantify the number of Vc neurons projecting to VPM or PBN after chronic constriction injury of the infraorbital nerve (ION-CCI) and subsequent upper-lip stimulation. ⋯ However, the percentage of pERK-IR VPM projection neurons was also greater in ION-CCI than sham rats after capsaicin but not mechanical lip stimuli. The present findings suggest that persistent trigeminal nerve injury increases the number of Vc neurons activated by capsaicin or mechanical lip stimuli. By contrast, trigeminal nerve injury modifies the proportion of Vc nociceptive neurons projecting to VPM and PBN in a stimulus modality-specific manner and may reflect differential involvement of ascending pain pathways receiving C fiber and mechanosensitive afferents.