Pain
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Opioid prescribing varies widely, and prescribed opioid dosages for an individual can fluctuate over time. Patterns in daily opioid dosage among patients prescribed long-term opioid therapy have not been previously examined. This study uses a novel application of time-series cluster analysis to characterize and visualize daily opioid dosage trajectories and associated demographic characteristics of patients newly initiated on long-term opioid therapy. ⋯ Time-series cluster analysis identified 2 clusters for each of the 3 baseline dosage categories <150 MME and 3 clusters for the baseline dosage category ≥150 MME. One cluster in each baseline dosage category comprised opioid dosage trajectories with decreases in dosage at the end of the follow-up period (80.7%, 98.7%, 98.7%, and 99.0%, respectively), discontinuation (58.5%, 80.0%, 79.3%, and 81.7%, respectively), and rapid tapering (50.8%, 85.8%, 87.5%, and 92.9%, respectively). These findings indicate multiple clusters of patients newly initiated on long-term opioid therapy who experience discontinuation and rapid tapering and highlight potential areas for clinician training to advance evidence-based guideline-concordant opioid prescribing, including strategies to minimize sudden dosage changes, discontinuation, or rapid tapering, and the importance of shared decision-making.
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Neuropilin-1 (NRP-1) is a transmembrane glycoprotein that binds numerous ligands including vascular endothelial growth factor A (VEGFA). Binding of this ligand to NRP-1 and the co-receptor, the tyrosine kinase receptor VEGFR2, elicits nociceptor sensitization resulting in pain through the enhancement of the activity of voltage-gated sodium and calcium channels. We previously reported that blocking the interaction between VEGFA and NRP-1 with the Spike protein of SARS-CoV-2 attenuates VEGFA-induced dorsal root ganglion (DRG) neuronal excitability and alleviates neuropathic pain, pointing to the VEGFA/NRP-1 signaling as a novel therapeutic target of pain. ⋯ Following in vivo editing of NRP-1, lumbar dorsal horn slices showed a decrease in the frequency of VEGFA-mediated increases in spontaneous excitatory postsynaptic currents. Finally, intrathecal injection of a lentivirus packaged with an NRP-1 guide RNA and Cas9 enzyme prevented spinal nerve injury-induced mechanical allodynia and thermal hyperalgesia in both male and female rats. Collectively, our findings highlight a key role of NRP-1 in modulating pain pathways in the sensory nervous system.
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Migraine is commonly reported in patients with temporomandibular disorders (TMDs), but little is known about the mechanisms underlying the comorbid condition. Here, we prepared a mouse model to investigate this comorbidity, in which masseter muscle tendon ligation (MMTL) was performed to induce a myogenic TMD, and the pre-existing TMD enabled a subthreshold dose of nitroglycerin (NTG) to produce migraine-like pain in mice. ⋯ Moreover, chemogenetic activation of Pdyn -expressing neurons or microinjection of dynorphin A (1-17) peptide in the Sp5C enabled a subthreshold dose of NTG to induce migraine-like pain in female mice but not in male mice. Taken together, our results suggest that trigeminal dynorphin has a female-specific role in the modulation of comorbid TMDs and migraine.
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The most recent prevalence estimate of post-traumatic headache (PTH) after traumatic brain injury (TBI) in veterans and civilians dates back to 2008. The prevalence was found to be 57.8%, with surprising higher rates (75.3%) in mild TBI when compared with those with moderate/severe TBI (32.1%). However, the revision of mild TBI diagnostic criteria and an historic peak of TBI in the elderly individuals attributed to the ageing population may lead to different results. ⋯ The overall prevalence of PTH after TBI over the past 14 years remains high even if assessed only in civilians. However, the prevalence rates attributed to mild and moderate/severe TBI were similar, differing significantly from previous reports. Efforts are needed to improve TBI outcomes.
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Multicenter Study
Brain-predicted age difference estimated using DeepBrainNet is significantly associated with pain and function-a multi-institutional and multiscanner study.
Brain age predicted differences (brain-PAD: predicted brain age minus chronological age) have been reported to be significantly larger for individuals with chronic pain compared with those without. However, a debate remains after one article showed no significant differences. Using Gaussian Process Regression, an article provides evidence that these negative results might owe to the use of mixed samples by reporting a differential effect of chronic pain on brain-PAD across pain types. ⋯ Moreover, brain-PAD was significantly related to multiple variables underlying the multidimensional pain experience. This comprehensive work adds evidence of pain type-specific effects of chronic pain on brain age. This could help in the clarification of the debate around possible relationships between brain aging mechanisms and pain.