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Kappa-opioid induced regulation of mu-opioid mediated effects on EEG power spectra and behavior in ratsThe regulatory effects of kappa-opioid ligands on mu-opioid induced changes in EEG power spectra and behavior were evaluated in rats receiving various acute and chronic treatments. Rats were implanted with cortical EEG electrodes and i.c.v. and/or intravenous (i.v.) cannulae. EEG spectral parameters were derived from digitized EEG samples with spectral analysis techniques. Pretreatment with intracerebroventricular (i.c.v.) injection of dynorphin, morphine and dynorphin/morphine resulted in quantitative and qualitative changes in EEG power spectra in rats given i.c.v. morphine 24 hr later. I.c.v. injections of morphine (20 {dollar}\mu{dollar}g/rat) produced high-voltage, slow-wave EEG bursts (1-10 Hz). Injections of i.c.v. morphine in rats pretreated with i.c.v. dynorphin (20 {dollar}\mu{dollar}g/rat), morphine (20 {dollar}\mu{dollar}g/rat) or dynorphin/morphine twenty-four hours earlier, produced quantitative increases in absolute EEG spectral power. Injections of i.c.v. morphine in rats pretreated with i.c.v. dynorphin/morphine 24 hr earlier, also produced qualitatively different EEG power spectra with a predominant peak in the 4-6 Hz band, similar to the EEG power spectra seen after acute administration of kappa opioids. Correlated changes in sensitivity to antagonism of these EEG effects by naloxone were also found. Thus, Dynorphin may act as a possible regulator of certain {dollar}\mu{dollar}-opioid receptor-associated phenomena, such as morphine-induced EEG bursts at a binding site which is nor-BNI insensitive. Chronic administration of morphine, a {dollar}\mu{dollar}-opioid selective agonist, for seven days resulted in tolerance development to EEG bursts and EEG absolute power, but not to latency to onset of slow-wave sleep (SWS). Chronic morphine administration was also associated with increases in the duration of hyperexcitability. Chronic administration of U-50,488H, a selective {dollar}\kappa{dollar}-agonist, was not associated with any changes in the duration of EEG bursts, latency to onset of SWS or duration of sedation. The coadministration of U-50,488H and morphine produced no significant tolerance development to the duration of EEG bursts and latency to onset of sleep, but increased the duration of sedation. Morphine or ethylketocyclazocine (EKC) challenges before and after chronic treatment with either morphine or U-50,488H resulted in greater tolerance development to the duration of EEG bursts and to increases in EEG absolute spectral power compared to the group receiving chronic coadministration. (Abstract shortened with permission of author.)
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A National Survey of Challenges Faced by Hospices During the Opioid Crisis: Estimates of Pain Medication Shortages, Missing Medications, and Opioids Left in the Home Post-DeathContext: No national data exist on hospice medication shortages, the frequency that opioid medications go missing, and drug disposal practices. Objectives: To provide national estimates for hospices on: drug shortages; frequency of missing medications; and opioids left in the home post-death. Methods: A national survey of 600 randomly selected hospices stratified by state and profit status (data collection 2018). Sample weights were applied to adjust for non-response. Respondents were hospice representatives knowledgeable about agency policies and practices. Participants reported their knowledge and perceptions about medication shortages, frequency that opioid medications go missing, and the proportion of hospice deaths in which opioids are left in the home. Findings were stratified by agency size. Results: 371 hospices completed surveys (response rate = 62%), half (50%) of which were mid-sized (26-100 patients), and not-for-profit. Respondents had 7.5 years (SD = 7.7) of agency experience. 42% of hospices – and 61% of large hospices – reported medication shortages. Among the full sample, 28% of agencies indicated shortages of morphine; 20% reported shortages of hydromorphone. Nearly half (43%) of hospice representatives reported that missing opioid medications occurred within the last 90 days. 52% of representatives reported employees are not allowed to dispose of medications after a home death; and, among home deaths, unused opioids were left in the home 32% of the time. This suggests opioid medications are frequently left in U.S. households after a hospice home death. Conclusion: Hospices face numerous challenges during the national opioid crisis. Interventions are needed to ensure access to needed treatments, mitigation of diversion, and safe medication disposal. © 2021 The Authors
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Opioid-galanin receptor heteromers mediate the dopaminergic effects of opioidsIdentifying nonaddictive opioid medications is a high priority in medical science, but μ-opioid receptors (MORs) mediate both the analgesic and addictive effects of opioids. We found a significant pharmacodynamic difference between morphine and methadone that is determined entirely by heteromerization of MORs with galanin Gal1 receptors (Gal1Rs), rendering a profound decrease in the potency of methadone. This finding was explained by the weaker proficiency of methadone in activating the dopaminergic system as compared with morphine and predicted a dissociation of the therapeutic and euphoric effects of methadone, which was corroborated by a significantly lower incidence of self-reports of feeling “high” in methadone-medicated patients. These results suggest that μ-opioid–Gal1R heteromers mediate the dopaminergic effects of opioids. The results further suggest a lower addictive liability of some opioids, such as methadone, due to their selective low potency for the μ-opioid–Gal1R heteromer.
