Articles: opioid.
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The ventrolateral periaqueductal gray (vlPAG) is a key structure in the descending pain modulatory circuit. Activation of the circuit occurs via disinhibition of GABAergic inputs onto vlPAG output neurons. In these studies, we tested the hypothesis that GABAergic inhibition is increased during persistent inflammation, dampening activation of the descending circuit from the vlPAG. Our results indicate that persistent inflammation induced by Complete Freund's adjuvant (CFA) modulates GABA signaling differently in male and female rats. CFA treatment results in increased presynaptic GABA release but decreased high-affinity tonic GABAA currents in female vlPAG neurons. These effects are not observed in males. The tonic currents in the vlPAG are dependent on GABA transporter activity and are modulated by agonists that activate GABAA receptors containing the δ subunit. The GABAA δ agonist THIP (gaboxadol) induced similar amplitude currents in naive and CFA-treated rats. In addition, a positive allosteric modulator of the GABAA δ subunit, DS2 (4-chloro-N-[2-(2-thienyl)imidazo[1,2-a]pyridin-3-yl]benzamide), increased tonic currents. These results indicate that GABAA δ receptors remain on the cell surface but are less active in CFA-treated female rats. In vivo behavior studies showed that morphine induced greater antinociception in CFA-treated females that was reversed with microinjections of DS2 directly into the vlPAG. DS2 did not affect morphine antinociception in naive or CFA-treated male rats. Together, these data indicate that sex-specific adaptations in GABAA receptor signaling modulate opioid analgesia in persistent inflammation. Antagonists of GABAA δ receptors may be a viable strategy for reducing pain associated with persistent inflammation, particularly in females. ⋯ These studies demonstrate that GABA signaling is modulated in the ventrolateral periaqueductal gray by persistent inflammation differently in female and male rats. Our results indicate that antagonists or negative allosteric modulators of GABAA δ receptors may be an effective strategy to alleviate chronic inflammatory pain and promote opioid antinociception, especially in females.
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J Craniomaxillofac Surg · Feb 2016
Randomized Controlled TrialAnalgesic effects of nefopam in patients undergoing bimaxillary osteotomy: A double-blind, randomized, placebo-controlled study.
Many studies have examined the postoperative analgesic effects of nefopam in various settings. However, although nefopam is expected to be useful in bimaxillary osteotomy, no published data are available. ⋯ Nefopam is an effective analgesic in bimaxillary osteotomy in that it can reduce the use of opioids and nonsteroidal anti-inflammatory drugs, thereby reducing the side effects of conventional analgesics. (
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Anaesth Crit Care Pain Med · Feb 2016
Randomized Controlled TrialImpact of preoperative continuous femoral blockades on morphine consumption and morphine side effects in hip-fracture patients: A randomized, placebo-controlled study.
Upon arrival at the emergency department, hip-fracture pain relief is usually carried out via systemic opioids. Continuous nerve blocks are efficient in the postoperative period, but have not been evaluated preoperatively. This study compared the reduction in morphine consumption and related side effects of a continuous femoral block with a single shot block in hip-fracture patients. ⋯ Preoperative continuous femoral blockades using ropivacaine reduce morphine side effects (mainly nausea) in hip-fracture patients without reducing morphine consumption.
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Support Care Cancer · Feb 2016
ReviewBreakthrough pain and its treatment: critical review and recommendations of IOPS (Italian Oncologic Pain Survey) expert group.
Controversies exist about the definition and epidemiology of breakthrough cancer pain (BTcP), the pharmacological treatment options, drug dosing, and how to select the medications for BTcP among the new fentanyl products. Existing data were critically evaluated to provide recommendations by an expert group. ⋯ The doses of opioids used for background pain should guide the choice of the doses of fentanyl products. The choice of fentanyl products should be based on individual clinical conditions.