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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Our objective was to elucidate the trends in non-medical use of prescription opioids (NMUPO) among whites, African-Americans, and Hispanic adolescents in the United States. An additional aim was to examine the sociodemographic, behavioral, and psychosocial correlates of NMUPO across each of these aforementioned racial and ethnic groups. ⋯ To our knowledge, this is the first study to identify a declining trend in NMUPO among adolescents. Although the present study findings provide a source for optimism, there is still a relatively high prevalence of NMUPO and it remains to be seen whether our findings portend a long-term decline. Given the harm done by NMUPO, continued awareness and targeted prevention efforts should be implemented.
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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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Observational Study
The relationship between overactivity and opioid use in chronic pain: a five day observational study.
With increasing concerns about the potential harm of long-term opioid therapy, there is a need for the development and implementation of alternative treatment strategies for patients with chronic pain who have been using opioids for a prolonged period of time. Based on the findings from a recent qualitative investigation that suggested there may be a bidirectional association between opioid reliance and habitual overactivity behaviour (activity engagement that significantly exacerbates pain), this study was designed to quantitatively investigate the association between opioid use and habitual overactivity over a 5-day period in a group of chronic pain patients. Participants provided a list of their prescribed pain medication, completed a self-report measure of habitual overactivity, and then commenced 5 days of data collection. ⋯ In addition, higher levels of habitual overactivity were associated with more frequent pro re nata ("as needed") opioid use over the 5 days, and with a discrepancy between the prescribed and actual oral morphine-equivalent daily dose, where more medication was taken than was prescribed. There was no predominant context for pro re nata use. The results of this study support the idea that habitual overactivity behaviour may play a role in the development of reliance on opioid medication and that such an association may provide a potential treatment target for opioid therapy rationalisation.
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There were over 23,000 opioid overdose deaths in the USA in 2013, and opioid-related mortality is increasing. Increased access to naloxone, particularly through community-based lay naloxone distribution, is a widely supported strategy to reduce opioid overdose mortality; however, little is known about the ecological and spatial patterns of the distribution and utilization of lay naloxone. This study aims to investigate the neighborhood-level correlates and spatial relationships of lay naloxone distribution and utilization and opioid overdose deaths. ⋯ Census tracts including or adjacent to a distribution site had higher income inequality, lower percentage black or African American residents, more drug arrests, higher population density, more overdose deaths, and more reversal events (all p < 0.05). In multivariable analysis, greater distance to the nearest distribution site (up to a distance of 4000 m) was associated with a lower count of Naloxone reversals [incidence rate ratio (IRR) = 0.51 per 500 m increase, 95% CI 0.39-0.67, p < 0.001] but was not significantly associated with opioid overdose deaths. These findings affirm that locating lay naloxone distribution sites in areas with high levels of substance use and overdose risk facilitates reversals of opioid overdoses in those immediate areas but suggests that alternative delivery methods may be necessary to reach individuals in other areas with less concentrated risk.