Articles: function.
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N-methyl-D-aspartate receptor (NMDAR) antagonists have been shown to reduce mechanical hypersensitivity in animal models of inflammatory pain. However, their clinical use is associated with significant dose-limiting side effects. Small-conductance Ca-activated K channels (SK) have been shown to modulate NMDAR activity in the brain. ⋯ Double immunostaining shows coexpression of SK3 and NMDAR subunit, NR1, compatible with functional interaction. Moreover, we demonstrate that i.t. coadministration of NS309 with an NMDAR antagonist reduces the dose of NMDAR antagonist, DL-2-amino-5-phosphonopentanoic acid (DL-AP5), required to produce antinociceptive effects in the CFA model. This reduction could attenuate the unwanted side effects associated with NMDAR antagonists, giving this combination potential clinical implications.
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Resting-state (RS) functional magnetic resonance imaging (fMRI) is a relatively novel tool which explores connectivity between functionally linked, but anatomically separated, brain regions. The use of this technique has allowed the identification, at rest, of the main brain functional networks without requiring subjects to perform specific active tasks. Methodologically, several approaches can be applied for the analysis of RS fMRI, including seed-based, independent component analysis-based and/or cluster-based methods. ⋯ RS functional connectivity is generally increased in pain-processing network, whereas is decreased in pain modulatory circuits. Significant abnormalities of RS functional connectivity occur also in affective networks, the default mode network and the executive control network. These results provide a strong characterization of migraine as a brain dysfunction affecting intrinsic connectivity of brain networks, possibly reflecting the impact of long lasting pain on brain function.
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Pain interventionists can interrupt pain through anesthetic blockade of neural transmission to virtually any part of the body. Temporary pain relief can be achieved by the direct application of targeted anesthetic. Diagnostically, nerve blocks help identify specific pain generators, refine differential diagnosis, and disrupt the neural transmission mechanisms to stop pain generation peripherally. ⋯ This study's results support the hypothesis that a combined interventional and cognitive motivational counseling treatment program can be effective in decreasing spine pain, reducing prescription pain medication use, and improving overall quality of life in chronic spine pain patients.
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Randomized Controlled Trial
Intravenous parecoxib and continuous femoral block for postoperative analgesia after total knee arthroplasty. A randomized, double-blind, prospective trial.
Up until now, the optimal strategy for postoperative pain management after total knee arthroplasty (TKA) remains to be elucidated. ⋯ According to our findings intravenous parecoxib in combination with continuous femoral block provided superior analgesic efficacy and opioid sparing effects in patients undergoing TKA.
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Critical care medicine · May 2015
Inhibition of Forkhead BoxO-Specific Transcription Prevents Mechanical Ventilation-Induced Diaphragm Dysfunction.
Mechanical ventilation is a lifesaving measure for patients with respiratory failure. However, prolonged mechanical ventilation results in diaphragm weakness, which contributes to problems in weaning from the ventilator. Therefore, identifying the signaling pathways responsible for mechanical ventilation-induced diaphragm weakness is essential to developing effective countermeasures to combat this important problem. In this regard, the forkhead boxO family of transcription factors is activated in the diaphragm during mechanical ventilation, and forkhead boxO-specific transcription can lead to enhanced proteolysis and muscle protein breakdown. Currently, the role that forkhead boxO activation plays in the development of mechanical ventilation-induced diaphragm weakness remains unknown. ⋯ Forkhead boxO is necessary for the activation of key proteolytic systems essential for mechanical ventilation-induced diaphragm atrophy and contractile dysfunction. Collectively, these results suggest that targeting forkhead boxO transcription could be a key therapeutic target to combat ventilator-induced diaphragm dysfunction.