Starting the Discussion: A Call to Enhance Care for People With Stimulant Use Disorder.

Stimulant use disorder (StUD) significantly contributes to substance-related morbidity and mortality in the United States. Overshadowed by the country's focus on opioid-related overdose deaths, stimulant and stimulant/opioid overdose deaths have increased dramatically over the last decade. Many individuals who use stimulants illicitly or have StUD have multiple, intersecting stigmatized characteristics which exacerbate existing barriers and create new obstacles to attaining addiction treatment. Illicit stimulant use, StUD, and stimulant-related overdose disproportionately impact minoritized racial and gender, and sexuality diverse groups. Historically, people who use illicit stimulants and those with StUD have been highly stigmatized, criminalized, and overly ignored by health care providers, policymakers, and the public compared to people who use other drugs and alcohol. As a result, most people needing treatment for StUD do not receive it. This is partly due to the lack of evidence-based treatment for StUD, which has resulted in few programs specializing in the care of people with StUD. The lack of available treatment is compounded by high rates of StUD in marginalized groups already reluctant to engage with the health care system. As health care professionals, we can improve outcomes for people with StUD by changing how we talk about, document, and respond to illicit stimulant use, related characteristics, behaviors, and social and structural determinants of health. To do this, we must seek to understand the lived realities of people with StUD and illicit stimulant use and use this knowledge to amend existing models of care.

Exploring the postoperative pain experiences of individuals with opioid use disorder and the nurses providing care in the USA: A qualitative descriptive study protocol.

INTRODUCTION: The goal of this study is to gain firsthand insights from individuals with a history of opioid use disorder (OUD) using medication for OUD on their experiences with postoperative pain care. This study also seeks to describe the experiences of nurses caring for individuals with OUD, and the challenges they may face managing complaints of pain in this population. Research suggests that hospitals can significantly enhance the quality of the care they deliver by investigating an individual's experience in the care setting. These insights will allow for the development of strategies for nurses to deepen their understanding of and, therefore, advocate and improve care for, this vulnerable and often stigmatised population. METHODS AND ANALYSIS: A qualitative descriptive study will be conducted consisting of a prescreening and demographics questionnaire, and individual semistructured interviews with approximately 10-15 individuals with OUD having recently undergone surgery and 10-15 nurses providing care for this population for a total of 20-30 interviews. This approach involves the collection of separate but complementary data (ie, perceptions of individuals with OUD and nurses) concerning the phenomena of postoperative pain management. Sampling will continue until data saturation is reached. Descriptive statistics and thematic analysis will then be used. Reporting will adhere to the Standards for Reporting Qualitative Research checklist. ETHICS AND DISSEMINATION: This study received approval from the Institutional Review Board at Northeastern University. Alongside peer-reviewed journal publications, the findings will be presented at relevant conferences, and a plain language summary will be distributed to the study participants.

Cholecystokinin acts in the dorsomedial hypothalamus of young male rats to suppress appetite in a nitric oxide-dependent manner.

Cholecystokinin (CCK) is an appetite-suppressing hormone that acts in the dorsomedial hypothalamus (DMH) in adult rats to suppress food intake. It remains unknown, however, whether CCK has the same affect in young animals, despite the rising prevalence of childhood obesity and drastic need for research in this area. At the synaptic level, CCK has been shown to inhibit putative orexigenic DMH neurons in young male rats by increasing GABA release onto these neurons via a CCK2 receptor and nitric oxide-dependent pathway. Whether this pathway leads to appetite suppression in young rats is not known. We therefore investigated whether intra-DMH administration of CCK, with or without inhibitors of the CCK2 receptor and nitric oxide signaling pathways, affects food intake in young, male, fasted Sprague-Dawley rats. We implanted bilateral guide cannulas into the DMH and allowed animals to recover from the surgery. Animals were then fasted for 24 h, following which they received intra-DMH microinjections of vehicle, CCK-8S, or CCK-8S combined with either LY-225910 (CCK2 receptor antagonist), L-NAME (a nitric oxide synthase inhibitor), or ODQ (a soluble guanylate cyclase inhibitor) and were given access to regular chow. Following a two hour refeeding period during which food intake, latency to feed, and body weight were measured, brains were subsequently removed to confirm cannula placement in the DMH. The effect of CCK on these parameters in rats given a high fat diet were also measured. Here we show that intra-DMH administration of CCK suppresses food intake and body weight in young rats. This effect requires activation of CCK2 receptors and nitric oxide signaling. Finally, CCK has no effect on consumption of a high fat diet when administered into the DMH. Overall, these findings demonstrate a potential pathway through which CCK might suppress appetite in young rats.

Nitric Oxide Acts in the Rat Dorsomedial Hypothalamus to Increase High Fat Food Intake and Glutamate Transmission.

The dorsomedial nucleus of the hypothalamus (DMH) plays an important role in the regulation of energy intake and expenditure. Numerous appetite-regulatory signals present in the DMH, including nitric oxide (NO) and endogenous cannabinoids (eCBs), act to regulate food intake, but whether these signals are involved in regulating high fat food intake remains unknown. We therefore asked whether NO and eCBs, administered alone or in combination, would influence the consumption of high fat food in rats. We implanted bilateral guide cannulas in the DMH of young, male Sprague-Dawley rats for microinjection of vehicle, NO (via the precursor l-arginine), the eCB 2-arachidonylglycerol (2-AG), or a combination of the two signals. Following the intrahypothalamic injections, both high fat food intake and body weight were measured for two hours at which point brains were removed and sectioned to confirm cannula placement in the DMH. Here we show that l-arginine significantly increases high fat food intake when administered into the DMH. This effect is abolished in the presence of 2-AG, which alone has no effect on high fat food intake or body weight. The l-arginine-induced increase in high fat food intake is dependent on NO synthesis, as it is prevented with the NO synthase inhibitor, l-NAME. We also demonstrate that l-arginine increases glutamate transmission onto DMH neurons, an effect that also requires NO synthesis and is abolished with 2-AG. Together, these data indicate that NO acts in the DMH to regulate the consumption of high fat food, possibly by enhancing glutamate signaling at DMH synapses.