Pain
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Pediatric surgeries are common and painful for children. Postoperative pain is commonly managed with analgesics; however, pain is often still problematic. Despite evidence for psychological interventions for procedural pain, there is currently no evidence synthesis for psychological interventions in managing postoperative pain in children. ⋯ Subgroup analysis indicated that distraction/imagery interventions were effective in reducing self-reported pain in the short term (24 hours, SMD = -0.63, 95% CI = -1.04 to -0.23), whereas preparation/education interventions were not effective (SMD = -0.27, 95% CI = -0.61 to 0.08). Data on the effects of interventions on longer term pain outcomes were limited. Psychological interventions may be effective in reducing short-term postoperative pain intensity in children, as well as longer term pain and other outcomes (eg, adverse events) require further study.
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This is the first large longitudinal cohort study to investigate the putative association of severe joint pain (SJP) with dipeptidyl peptidase-4 inhibitor (DPP4i) use in patients with type 2 diabetes. The propensity score-matched population-based cohort study was performed between 2009 and 2013 in a group of type 2 diabetes patients with stable metformin use. In total, 4743 patients with type 2 diabetes used a DPP4i as the second-line antidiabetic drug (ie, DPP4i users), and the same number of matched non-DPP4i users was selected. ⋯ Cox proportional hazard model indicated that DPP4i use slightly but nonsignificantly reduced the risk of SJP (adjusted hazard ratio: 0.92 [95% CI: 0.83-1.02]). Such null results were also observed among all age and sex stratifications and in a sensitivity analysis using all nonspecific arthropathies as the study endpoint. This study provides no support for the putative risk of SJP related to DPP4i use in type 2 diabetes patients during a maximum follow-up of 5 years.
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Repeated sensory exposures shape the brain's function and its responses to environmental stimuli. An important clinical and scientific question is how exposure to pain affects brain network activity and whether that activity is modifiable with training. We sought to determine whether repeated pain exposure would impact brain network activity and whether these effects can be reversed by cognitive behavioral therapy (CBT)-based training. ⋯ Finally, the regulate group showed enhanced resting functional connectivity between areas of the DMN and executive control network over time, compared with the control group. Our study demonstrates that trainable cognitive states can alter the effect of repeated sensory exposure on the brain. The findings point to the potential utility of cognitive training to prevent changes in brain network connectivity that occur with repeated experience of pain.
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Uncoupling the protein-protein interaction between collapsin response mediator protein 2 (CRMP2) and N-type voltage-gated calcium channel (CaV2.2) with an allosteric CRMP2-derived peptide (CBD3) is antinociceptive in rodent models of inflammatory and neuropathic pain. We investigated the efficacy, duration of action, abuse potential, and neurobehavioral toxicity of an improved mutant CRMP2 peptide. A homopolyarginine (R9)-conjugated CBD3-A6K (R9-CBD3-A6K) peptide inhibited the CaV2.2-CRMP2 interaction in a concentration-dependent fashion and diminished surface expression of CaV2.2 and depolarization-evoked Ca influx in rat dorsal root ganglia neurons. ⋯ Continuous subcutaneous infusion of R9-CBD3-A6K over a 24- to 72-hour period reversed tactile allodynia and ongoing pain, demonstrating a lack of tolerance over this time course. Importantly, continuous infusion of R9-CBD3-A6K did not affect motor activity, anxiety, depression, or memory and learning. Collectively, these results validate the potential therapeutic significance of targeting the CaV-CRMP2 axis for treatment of neuropathic pain.
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Loss of high-voltage-activated (HVA) calcium current (ICa) and gain of low-voltage-activated (LVA) ICa after painful peripheral nerve injury cause elevated excitability in sensory neurons. Nerve injury is also accompanied by increased expression of the extracellular matrix glycoprotein thrombospondin-4 (TSP4), and interruption of TSP4 function can reverse or prevent behavioral hypersensitivity after injury. We therefore investigated TSP4 regulation of ICa in dorsal root ganglion (DRG) neurons. ⋯ In the neuropathic pain model of spinal nerve ligation, TSP4 application did not further regulate ICa of injured DRG neurons. Taken together, these findings suggest that elevated TSP4 after peripheral nerve injury may contribute to hypersensitivity of peripheral sensory systems by decreasing HVA and increasing LVA in DRG neurons by targeting the α2δ1 calcium subunit. Controlling TSP4 overexpression in peripheral sensory neurons may be a target for analgesic drug development for neuropathic pain.