Direct effects of heroin and methadone on T cell function.

Opioid addiction presents a relevant health challenge, with chronic heroin use linked to detrimental effects on various aspects of physical, mental, and sociological health. Opioid maintenance therapy (OMT), particularly using methadone, is the primary treatment option for heroin addiction. Previous studies using blood samples from current heroin addicts and OMT patients have shown immunomodulatory effects of heroin and methadone on T cell function. However, various additional factors beyond heroin and methadone affect these results, including the consumption of other substances, a stressful lifestyle, comorbid psychological and somatic disorders, as well as additional medications. Therefore, we here investigated the direct effects of heroin and methadone on purified human T cells in vitro. Our results reveal that both, heroin and methadone directly suppress Tcell activation and proliferation. Strikingly, this inhibitory effect was markedly stronger in the presence of methadone, correlating with a decrease in secretion of pro-inflammatory cytokines. While heroin did not interfere with the in vitro differentiation and expansion of regulatory Tcells (Tregs), methadone significantly impaired the proliferation of Tregs. Overall, our findings suggest a direct inhibitory impact of both opioids on effector T cell function in vitro, with methadone additionally interfering with Treg induction and expansion in contrast to heroin.

Estimating price elasticities of demand for pain relief drugs: evidence from Medicare Part D.

Overdose deaths from prescription opioids remain elevated, and policymakers seek solutions to curb opioid misuse. Recent proposals call for price-based solutions, such as opioid taxes and removal of opioids from insurance formularies. However, there is limited evidence on how opioid consumption responds to price stimuli. This study addresses that gap by estimating the effects of prices on the utilization of opioids, as well as other prescription painkillers. I use nationally representative individual-level data on prescription drug purchases and exploit the introduction of Medicare Part D in 2006 as an exogenous change in out-of-pocket drug prices. I find that new users have a relatively high price elasticity of demand for prescription opioids, and that consumers treat over-the-counter painkillers as substitutes for prescription painkillers. My results suggest that increasing out-of-pocket prices of opioids, through formulary design or taxes, may be effective in reducing new opioid use.

Metabolic characterization of the new benzimidazole synthetic opioids - nitazenes.

The recent re-emergence and the increasing popularity of nitazenes, a group of new synthetic opioids (NSO) that belong to the benzimidazole chemical class, has raised public health concerns. As a class of potential opioid analgesic agents whose development was discontinued in the 1960s due to their high potential for abuse, very little is known about their metabolism and physiologic disposition. In the current study, three nitazenes-butonitazene, isotonitazene and protonitaze were incubated in human liver microsomes (HLM), human S9 (HS9) fractions and recombinant cytochrome P450 enzymes. All three nitazenes were rapidly metabolized in both HLM and HS9 with over 95% depletion within 60 min. In HLM, butonitazene, isotonitazene and protonitazene had in vitro intrinsic clearance (CLint) (µL/min/mg protein) values of 309, 221 and 216 respectively compared to 150 of verapamil, the positive control. In HS9, CLint values were 217, 139, and 150 for butonitazene, isotonitazene and protonitazene respectively compared to only 35 for testosterone, the control probe substrate. Putative metabolite identified from this study include products of hydroxylation, desethylation, dealkylation, desethylation followed by dealkylation, and desethylation followed by hydroxylation. The metabolic phenotyping showed CYP2D6, CYP2B6 and CYP2C8 and the major hepatic enzymes responsible for the metabolism of nitazenes. Within 30 min of incubation, CYP2D6 depleted butonitazene (99%), isotonitazene (72%) and butonitazene (100%) significantly. The rapid metabolism of nitazenes may be an important factor in accurate and timely detections and quantitation of the unchanged drugs in human matrices following intoxication or in forensic analysis. The involvement of multiple polymorphic CYPs in their metabolism may play important roles in the susceptibility to intoxication and/or addiction, depending on the activity of the metabolites.

Exploring Xylazine Awareness, Health Impacts, and Harm Reduction Strategies: Findings From a Multimethods Study in Lowell, Massachusetts.

BACKGROUND: Xylazine, an adulterant in local drug supplies, has been detected in approximately 30% of opioid samples submitted for testing in Massachusetts. A better understanding of local risks, harms, and use preferences is needed to combat xylazine-related impacts on local communities. METHODS: Through the STOP-OD Lowell study, we aimed to assess local xylazine awareness through in-depth interviews with local community stakeholders (n = 15) and local people who use drugs (PWUD; n = 15) and surveys with local PWUD (n = 94). The qualitative interviews focused on the current drug landscape and knowledge of adulterants in Lowell, and the results informed subsequent survey design. Through our survey, we examined whether PWUD were aware of xylazine and their willingness to use xylazine test strips. RESULTS: Most community stakeholders and PWUD had limited awareness about the presence and impact of xylazine as an adulterant. Forty-seven (50%) survey respondents were aware of xylazine. When provided with more information about xylazine, 65% of all respondents expressed a willingness to use xylazine test strips. PWUD who had received naloxone training, reported using with others, and using tester shots were more willing to use xylazine test strips. CONCLUSION: Our findings are congruent with existing literature that indicates that there is limited awareness of xylazine among PWUD, and they consider xylazine an unwanted adulterant. We also found that PWUD who use other harm reduction measures are more willing to use xylazine test strips. The increase in xylazine warrants additional community-level interventions such as wound management and local testing infrastructure. Further research is needed to understand better the impacts associated with xylazine use, effective harm reduction techniques, and perceptions of xylazine test strips.

A pilot study on post-mortem determination of drug abuse on dental tissues.

BACKGROUND: Post-mortem toxicology constantly deals with the research of reliable alternative matrices to be applied in case of highly damaged corpses (such us carbonized, skeletonized, human remains, etc.). Teeth represent a promising alternative matrix since dental tissues are endowed by different features, resistance and stability after death. SCOPE: Since scant literature reported on the pharmacokinetics and mechanism of incorporation of xenobiotics into dental tissues, this pilot research aims to investigate whether in the pulp can be detected the same substances found in blood in drug related death cases. Secondly, the study is addressed to disclose the possible deposit of drugs in dental hard tissues (dentine and/or enamel), thus contributing to reconstruct the drug abuse history (timing, e.g.). MATERIALS AND METHODS: The study experimented with a novel method to separately analyse dental enamel, dentin, and pulp, applied to 10 teeth collected during autopsies of drug-related deaths along with blood and hair samples for classic toxicological analyses. Each tooth was prepared by "pulverization technique" and then analysed by gas chromatography paired with mass spectrometry (GC-MS) and ultra high performance liquid chromatography coupled to high resolution mass spectrometry (UHPLC/HR-MS) for searching cocaine, opiates, and metabolites. The results were then compared with those obtained from blood and hair samples. RESULTS: Preliminary results demonstrated that teeth differ from any other classic matrix (blood and hairs) since the qualitative correspondence of the detected substances between pulp and blood as well as dental hard tissues and hair suggests that they can be useful in post-mortem evaluation as a unique matrix for both acute and chronic assumptions of drugs. The mechanism of accumulation of substances in mineralized dental tissues emerged the most significant result, being influenced by the type of molecule and the method of assumption. The main limitation of this study is the limited availability of the sample and the absence of anamnestic information of the time, rates and method of drug assumption during life. Further research is necessary to systematically investigate the distribution of different substances within the different tissues of the tooth.

Perioperative opioids in high-risk children undergoing tonsillectomy - A single institution experience.

BACKGROUND: Patients undergoing tonsillectomy/ adenotonsillectomy (T/AT) can experience substantial postoperative pain. The aims of this study are to assess perioperative pain management in high-risk children (children with severe obstructive sleep apnea and other complex medical comorbidities or age younger than 2 years) undergoing T/AT, and the impact on oxygen levels and pain during extended Post-Anesthesia Care Unit (PACU) admission. METHODS: A retrospective case series study at a tertiary care children's hospital. RESULTS: There were 278 children enrolled in the study. The Apnea-Hypopnea index and mean oxygen nadir on preoperative polysomnography were 31.3 ± 25.76/h and 79.5 ± 9.5 % respectively. Overall, 246 (89 %) patients received intraoperative opioids alone (n = 35, 13 %) or in combination with non-opioid analgesia (n = 209, 75 %). While the median dose of opioid-free medications (acetaminophen, ibuprofen) ranged from 93 to 100 % of standard maximal dosing by weight and age, the median dose of opioids was significantly lower and ranged from 54 to 63 % of standard maximal dosing by weight and age, with 43 % of the patients receiving less than half the recommended maximum dose. Oxygen desaturation was charted in 21 patients (8 %) during their PACU admission. Patients who received opioid-free analgesia were as likely to develop oxygen desaturations (n = 17 (81 %) vs. n = 228 (89.4 %), p = 0.27) and to receive rescue pain medication during their PACU stay as patients who received opioids intraoperatively (n = 18 (56 %) vs. n = 167 (68 %), p = 0.23). CONCLUSIONS: Intraoperative pain management varies across high-risk pediatric tonsillectomies. Opioid-free analgesia was not associated with an increased need for pain medications during PACU admission, or with a decreased likelihood of oxygen desaturations compared to intra-operative opioid analgesia use.

Management of pain in the inpatient and non-surgical outpatient dermatology settings: A narrative review.

Pain is frequently encountered in dermatology practice, which impairs the activities of daily living, adds to psychological morbidity, and therefore compromises the quality of life. It ranges from mild to severe in intensity across various dermatoses and requires prompt addressal and treatment. Diseases such as extensive pemphigus vulgaris and Stevens-Johnson syndrome are especially painful and require a multidisciplinary approach with the involvement of a pain specialist in their management. The main pathogenic types of pain include visceral nociceptive, somatic nociceptive, and neuropathic types, the latter two being most relevant in dermatological disorders. Somatic nociceptive pain is often seen in patients of Stevens-Johnson syndrome/ Toxic epidermal necrolysis, epidermolysis bullosa, pemphigus vulgaris, erythema nodosum, and hidradenitis suppurativa, while neuropathic pain is part of the disease process in dermatoses like leprosy, herpes zoster, and dysesthesia syndromes. Therapeutic approaches to pain management include the use of non-opioids (acetaminophen, non-steroidal anti-inflammatory agents), opioids, and non-pharmacological therapies, along with appropriate management of the underlying dermatosis. World Health Organisation (WHO) analgesic ladder remains the most commonly employed guideline for the management of pain, although treatment needs individualisation depending on the nature and severity of pain (acute/chronic), type of dermatosis, and patient factors. There is a paucity of literature pertaining to pain management in dermatology and this topic is often neglected due to a lack of awareness and knowledge of the topic. The present review aims to discuss the pain pathway, various painful conditions in the setting of medical dermatology practice, and their management along with relevant pharmacology of the commonly used analgesics.

The role of metaphor in the corporate political strategies of health harming industries: Comparing the concept of balance in the gambling and opioid industry discourses.

Scholars have identified notable similarities between the political strategies employed by health-harming industries. This includes similarities in the narratives employed by industry actors seeking to oppose public health regulations that threaten their commercial interests. This study seeks to examine the use of a specific concept - the balance metaphor - in the policy discourses of two health-harming industries. Namely, the pharmaceutical industry implicated in the prescription opioid crisis in the US, and the UK gambling industry, whose products and practices are associated with a serious, but largely neglected, series of harms. We first review research on metaphors, demonstrating how this provides additional theoretically-informed concepts with which to understand how industry discourse circumscribes the terrain of policy debates in ways amenable to commercial interests. Building from these insights, we conducted a rhetorical analysis, examining how the concept of balance is employed by different actors in distinct contexts to shape understandings of the social and policy problems associated with gambling and opioid products and to promote industry-favourable regulatory responses to these. This brings a micro-level of analysis to supplement previous meso- and macro-level scholarship in this space. We use our findings to argue that the depoliticization of the policy process and objectivization of the policy space - in ways that obscure its contingent and political nature - through discourses of balance is itself an arch political act. Examining the metaphors used in policy debates and their functions provides important insights that can be used to inform the construction of counter-narratives to industry-favourable discourses, including the creative use of novel metaphors in the service of public health goals.

Can mind-altering prescription medicines be safe? Lessons from ketamine and esketamine.

INTRODUCTION: Recent decades have witnessed an extraordinary global crisis of drug misuse. Although opioid analgesics receive the most attention, numerous other drugs have increased rates of misuse. KETAMINE AND ESKETAMINE: Ketamine and esketamine offer a unique natural experiment to explore two medications that are similar pharmacologically but differ in their availability to users and in their regulation by government agencies. MISUSE AND ABUSE OF KETAMINE AND ESKETAMINE: Multisystem "mosaic" surveillance of many drugs using real-world data has emerged in recent years. Ketamine and esketamine have been monitored concurrently. Ketamine is much more widely available than esketamine and shows clear signs of increasing misuse and abuse. In contrast, esketamine is difficult to detect in postmarket surveillance even though availability is increasing. DISCUSSION: Ketamine and esketamine offer insights regarding the safety of prescription medications with the potential for misuse. Since the pharmacology of ketamine and esketamine are similar, the regulatory apparatus may be the primary difference that limits misuse. Ketamine has few restrictions and can be prescribed or administered by many healthcare providers, and is available as an illicit drug. In contrast, the product labeling for esketamine has rigorous restrictions on its use. Many important issues remain to be addressed. We need a more rigorous evaluation of the natural experiment of ketamine and esketamine. How does this experience relate to the introduction of new psychedelics? CONCLUSIONS: Ketamine misuse use and misuse are increasing while esketamine use in increasing, but misuse is not increasing. It is reasonable to reevaluate the regulatory controls on ketamine to reduce its misuse and abuse.

Global trends in opioid use for pain management in acute pancreatitis: A multicentre prospective observational study.

BACKGROUND: Since there is no current international consensus on the optimal approach for pain management in acute pancreatitis (AP), analgesic practices may vary across different healthcare settings. OBJECTIVE: This study explored global disparities in analgesic use, in particular opioids, during admission and at discharge in hospitalised AP patients. METHODS: This was a post hoc analysis of the prospective PAINAP database, which included all admissions for AP between April and June 2022 with a 1-month follow-up. Demographic details, analgesic use, and clinical outcomes were recorded during admission and at discharge. Odds ratios (ORs) for opioid use during admission and at discharge were identified using multivariable regression analyses. RESULTS: Amongst the 1864 patients (52% males, median age 56 (interquartile range, 41-71)) across three different continents, simple analgesics were predominantly used as the primary analgesic (70%). Opioid use during admission was lowest in European centres (67%). Admission in Asian (OR, 2.53 (95% confidence interval (CI), 1.59-4.04), p < 0.001), and Australian (OR, 5.81 (95% CI, 3.19-10.56), p < 0.001) centres was associated with opioid administration during admission compared with European centres. Increased pain severity, longer pre-admission pain duration, organ failure, and longer length of admission increased opioid use during admission. At discharge, Asian (OR, 2.01 (95% CI, 1.40-2.88), p < 0.001) and Australian (OR, 1.91 (95% CI, 1.28-2.85), p = 0.002) centres were associated with opioid prescription compared with European centres. Increased pain severity, longer pre-admission pain duration, acute necrotic collections, and walled-off necrosis also increased the likelihood of opioid prescription at discharge. CONCLUSION: There are substantial intercontinental differences in opioid use for AP pain. Accordingly, there is a need for international guidelines on pain management in AP.

The associations of supervised consumption services with the rates of opioid-related mortality and morbidity outcomes at the public health unit level in Ontario (Canada): A controlled interrupted time-series analysis.

INTRODUCTION: This study aimed to assess the impact of the implementation of legally sanctioned supervised consumption sites (SCS) in the Canadian province of Ontario on opioid-related deaths, emergency department (ED) visits and hospitalisations at the public health unit (PHU) level. METHODS: Monthly rates per 100,000 population of opioid-related deaths, ED visits and hospitalisations for PHUs in Ontario between December 2013 and March 2022 were collected. Aggregated and individual analyses of PHUs with one or more SCS were conducted, with PHUs that instituted an SCS being matched to control units that did not. Autoregressive integrated moving average models were used to estimate the impact of SCS implementation on opioid-related deaths, ED visits and hospitalisations. RESULTS: Twenty-one legally sanctioned SCS were implemented across nine PHUs in Ontario during the study period. Interrupted time series analyses showed no statistically significant changes in opioid-related death rates in aggregated analyses of intervention PHUs (increase of 0.02 deaths/100,000 population/month; p = 0.27). Control PHUs saw a significant increase of 0.38 deaths/100,000 population/month; p < 0.001. No statistically significant changes were observed in the rates of opioid-related ED visits in intervention PHUs (decrease of 0.61 visits/100,000 population/month; p = 0.39) or controls (increase of 0.403 visits; p = 0.76). No statistically significant changes to the rates of opioid-related hospitalisations were observed in intervention PHUs (0 hospitalisations/100,000 population/month; p = 0.98) or controls (decrease of 0.05 hospitalisations; p = 0.95). DISCUSSION AND CONCLUSIONS: This study did not find significant mortality or morbidity effects associated with SCS availability at the population level in Ontario. In the context of a highly toxic drug supply, additional interventions will be required to reduce opioid-related harms.

Negative allosteric modulation of CB1 cannabinoid receptor signalling decreases intravenous morphine self-administration and relapse in mice.

The endocannabinoid system interacts with the reward system to modulate responsiveness to natural reinforcers, as well as drugs of abuse. Previous preclinical studies suggested that direct blockade of CB1 cannabinoid receptors (CB1R) could be leveraged as a potential pharmacological approach to treat substance use disorder, but this strategy failed during clinical trials due to severe psychiatric side effects. Alternative strategies have emerged to circumvent the side effects of direct CB1 binding through the development of allosteric modulators. We hypothesized that negative allosteric modulation of CB1R signalling would reduce the reinforcing properties of morphine and decrease behaviours associated with opioid misuse. By employing intravenous self-administration in mice, we studied the effects of GAT358, a functionally-biased CB1R negative allosteric modulator (NAM), on morphine intake, relapse-like behaviour and motivation to work for morphine infusions. GAT358 reduced morphine infusion intake during the maintenance phase of morphine self-administration under a fixed ratio 1 schedule of reinforcement. GAT358 also decreased morphine-seeking behaviour after forced abstinence. Moreover, GAT358 dose dependently decreased the motivation to obtain morphine infusions under a progressive ratio schedule of reinforcement. Strikingly, GAT358 did not affect the motivation to work for food rewards in an identical progressive ratio task, suggesting that the effect of GAT358 in decreasing opioid self-administration was reward specific. Furthermore, GAT58 did not produce motor ataxia in the rotarod test. Our results suggest that CB1R NAMs reduced the reinforcing properties of morphine and could represent a viable therapeutic route to safely decrease misuse of opioids.

U.S. trends in methamphetamine-involved psychiatric hospitalizations in the United States, 2015-2019.

BACKGROUND: In the U.S., overdose deaths and substance treatment admissions related to methamphetamine are rising. This study aims to measure and compare U.S. temporal trends in methamphetamine-involved psychiatric hospitalizations. METHODS: We conducted a population-based, trend analysis of U.S. psychiatric hospitalizations and calculated quarterly (Q) rates per 100,000 population of substance-involved psychiatric hospitalizations. We assessed U.S. regional quarterly percentage hospitalization rate changes using Joinpoint regression. RESULTS: From Q4 2015-Q4 2019, there were 963,202 psychiatric hospitalizations, 50,223 (5.2 %) involved methamphetamine and 102,877 (10.7 %) involved opioids and/or cocaine without methamphetamine. Methamphetamine-involved psychiatric hospitalization rates increased by 68.0 %, psychiatric hospitalizations rates involving opioid and/or cocaine without methamphetamine decreased by 22 %, while nonsubstance-involved psychiatric hospitalizations rates remained unchanged. The largest significant increases in methamphetamine-involved psychiatric hospitalization rates were among people >61 years old, males, and Midwesterners. Methamphetamine-involved psychiatric hospitalization rates doubled among Black patients. The largest average percent increase among methamphetamine-involved psychiatric hospitalizations was 10.2 % from Q4 2015-Q2 2017 in the Midwest. CONCLUSION AND RELEVANCE: Most psychiatric hospitalizations did not involve substances. Methamphetamine-involved psychiatric hospitalizations greatly increased while opioid-involved psychiatric hospitalizations decreased, but involved more total encounters. Greater access to harm reduction services, contingency management programs, and mental health services is urgently needed.

Efficacy and safety of hydromorphone for cancer pain: a systematic review and meta-analysis.

BACKGROUND: Cancer pain significantly impacts individuals' quality of life, with opioids being employed as the primary means for pain relief. Nevertheless, concerns persist regarding the adverse reactions and effectiveness of opioids such as morphine. Hydromorphone, recognized as a potent opioid, is a viable alternative for managing cancer-related pain. The goal of this systematic review and meta-analysis was to determine the effectiveness and safety characteristics of hydromorphone in comparison to other opioids, as well as different methods of administering this medication within the scope of cancer pain treatment. METHODS: The PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases were searched on December 25th, 2023. Following the PRISMA guidelines, a systematic investigation of databases was carried out, and suitable studies were chosen according to predetermined criteria (PICO framework). The meta-analyses were performed using a random-effects model. RESULTS: This review included 18 RCTs with 2271 patients who compared hydromorphone with morphine, oxycodone, or fentanyl, as well as other types of hydromorphone. Hydromorphone demonstrated efficacy similar to that of morphine and oxycodone in reducing cancer pain intensity, decreasing additional analgesic consumption, and improving quality of life. However, morphine showed slight superiority over hydromorphone in reducing breakthrough pain. Adverse events were comparable between hydromorphone and morphine or oxycodone. Patient-controlled and clinician-controlled hydromorphone administration routes yielded similar outcomes. CONCLUSIONS: The outcomes of this study substantiate the efficacy of hydromorphone in the management of cancer-related pain, demonstrating similar levels of effectiveness and safety as morphine and oxycodone. These findings are consistent with prior comprehensive analyses, suggesting that hydromorphone is a feasible choice for alleviating cancer-associated pain. Additional investigations are warranted to determine its efficacy in distinct patient cohorts and for different modes of administration. TRIAL REGISTRATION: Prospero registration ID: CRD42024517513. Link: https://www.crd.york.ac.uk/PROSPERO/#recordDetails .

Comparison ultrasound-guided adductor canal block and surgeon-performed block for pain management after total knee arthroplasty: a prospective randomized controlled study.

OBJECTIVE: Adductor canal block (ACB) is widely performed for postoperative analgesia for total knee arthroplasty (TKA). The aim of this study is to compare surgeon-assisted and anesthesiologist-assisted (ultrasound-guided) adductor blocks in terms of postoperative analgesic efficacy. METHODS: This study was designed as a double-blind, prospective and randomized trial. A total of 240 participants were randomly allocated to three groups: one where the surgeon performed the adductor canal block (ACBs), another where it was conducted by an anesthetist with ultrasound guidance (ACBa), and a third group without the adductor block. The follow-up management after the Total Knee Arthroplasty (TKA) procedure occurred on the first, third, and tenth days, as well as the twelfth week. Outcome measures comprised pain assessment using the Visual Analog Scale (VAS) and monitoring opioid analgesic consumption. RESULTS: No significant differences in demographic profiles were observed between the groups. Groups ACBa and ACBs exhibited significantly lower VAS scores compared to the control group at both 3 and 12 h after surgery, with group ACBa showing the lowest VAS scores among all groups. However, at 1 day, 3 days, 10 days and 12 weeks after surgery, there was no significant difference in VAS scores between the ACBa and ACBs groups. On the first three days, the ACBa group had the lowest opioid consumption and the lowest total opioid consumption. The differences in VAS scores between the groups began to decrease on the first day after surgery. CONCLUSION: The adductor canal block (ACB) has been demonstrated to be an effective method of reducing pain in patients undergoing total knee replacement (TKR) in the postoperative period. Nevertheless, despite the pronounced impact that ACB performed by an anesthesiologist under ultrasound guidance has on VAS scores according to intraoperative ACB by surgeons, its effect on clinical outcomes has not been demonstrated. TRIAL REGISTRATIONS: This study was retrospectively registered with the Clinical Trials Registry Platform on July 31, 2024 (NCT06533085).

Association Between Low-Dose Ketamine After Periacetabular and/or Femoral Osteotomy and Postoperative Opioid Requirements.

Background: Previous studies have sought to determine the effect of inpatient ketamine therapy on postoperative pain in a variety of surgical specialties. Purpose: To determine the effects of postoperative ketamine analgesia after periacetabular osteotomy (PAO) and/or derotational femoral osteotomy (DFO) on opioid requirements, pain, and discharge time. Study Design: Cohort study; Level of evidence, 3. Methods: Prospective data were collected on 145 patients who underwent PAO and/or DFO by the senior author between January 2021 and December 2022. Hip arthroscopy was performed 3 to 10 days before addressing any intra-articular pathology. In 2021, patients (n = 91 procedures; control group) received a traditional postoperative multimodal pain regimen. In 2022, postoperative low-dose ketamine (0.1-1 mg/kg/h) was added to the multimodal analgesic approach until 24 hours before discharge (n = 81 procedures; ketamine group). The ketamine and control groups were matched based on procedure type. Total opioid consumption was collected using milligram morphine equivalents (MMEs) for both groups. Postoperative pain was measured using the Defense and Veterans Pain Rating Scale (DVPRS), which was analyzed as the mean score per day. Data on the mean MME and DVPRS were analyzed for up to 7 days postoperatively. Linear mixed statistical analysis was performed to determine the significance of low-dose postoperative ketamine on postoperative pain and opioid utilization. Results: Patients who did not receive ketamine after PAO and/or DFO utilized a mean of 181 ± 335 MMEs and had a mean DVPRS score of 4.18 ± 1.63. Patients who received postoperative ketamine required a mean of 119 ± 291 MMEs and had a mean DVPRS score of 4.34 ± 1.61. The ketamine group was found to consume a significantly lower total MME dose per day (P < .001). No significant difference was found in the mean DVPRS score between the ketamine and control groups (P = .42). Also, no significant difference was found on the day of discharge (P = .79). Conclusion: Patients who received postoperative ketamine after PAO and/or DFO had a significant decrease in MME dose when compared with a control group of patients who did not receive ketamine. Surgeons should consider adding ketamine to their postoperative multimodal pain control protocol to decrease opioid consumption while adequately addressing postoperative pain.

Voluntary wheel running access produces opposite effects in male and female rats on both palatable diet consumption and associated ventral striatal opioid- and dopamine-related gene expression.

The relationship between physical activity levels and feeding behaviors has been a focus of preclinical research for decades, yet this interaction has only recently been explored for potential sex differences. The aim of the present study was to isolate sex-dependent effects of voluntary wheel running (RUN) vs. sedentary locked wheel (SED) home cage conditions on palatability-driven feeding behavior using a 2-diet choice task between standard chow and a high-fat diet. The sex-dependent effects of physical activity on feeding behavior were examined following a within-subject novel reversal design of physical activity conditions (i.e., RUN > SED > RUN), to assess temporal sensitivity of the interaction. Following the final 2 weeks of reestablished and sustained RUN vs. SED conditions in separate groups of both males and females, reward-related opioid and dopamine gene expression within the nucleus accumbens (Acb) brain region were analyzed. Results demonstrated that the initial RUN > SED transition led to sex-dependent effects of SED condition, as males increased, and females decreased their high fat consumption, compared to their respective high fat consumption during previous RUN condition phase. Following reintroduction to the RUN condition, males decreased, and females increased their high fat consumption, compared to their separate SED control group. Last, sex-dependent shifts in ventral striatal opioid- and dopamine-related gene expression were observed to parallel the behavioral effects. The major findings of the study reveal that SED and RUN home cage conditions shift palatability-driven feeding in the opposite direction for males and females, these effects are sensitive to reversal, and these sex-dependent feeding behaviors track sex-dependent changes to critical reward-related gene expression patterns in the Acb. Considering the present high rates of sedentary behavior and obesity, furthering our understanding of the interaction between physical activity (or lack thereof) and feeding behavior should be a priority, especially in the context of these divergent sex-dependent outcomes.

A Retrospective Observation of Gasserian Ganglion Pulsed Radiofrequency Therapy Combined with Low-Dose Morphine Injection in the Treatment of Ophthalmic Herpetic Neuralgia.

Purpose: This retrospective study was to investigate the efficacy of Gasserian ganglion pulsed radiofrequency therapy (PRF) combined with low-dose morphine injection in the treatment of refractory ophthalmic herpetic neuralgia. Patients and methods: A total of 40 intractable ophthalmic herpetic neuralgia patients who received Gasserian ganglion PRF therapy in Pain Department of Nanjing Drum Tower Hospital were retrospectively analysed, with an average age of 70.2 ± 8.5 years and an average disease course of 30 (30, 60) days. According to different interventions, they were divided into two groups: Group A, 19 patients who received Gasserian ganglion PRF therapy combined with 0.2 mg morphine injection via puncture needle; Group B, 21 patients who received only Gasserian ganglion PRF therapy. Data related to the length of hospital stay and associated costs, numerical rating scale scores (NRS), intravenous morphine and oral oxycodone doses during hospitalization, Short form McGill pain questionnaire and Pittsburgh sleep quality index (PSI), and conditions of opioid use and postherpetic neuralgia after discharge were collected in the two groups. SPSS 25.0 was used to perform statistical analysis on data. Results: The hospital stay, hospitalization costs, and oxycodone dosages for Group A were lower than those for Group B (p = 0.02, p = 0.015 and p = 0.023, respectively). The proportion of patients in group A still taking oral opioids 1 month after discharge and experiencing postherpetic neuralgia 6 months after the onset was lower than that in group B (p = 0.004 and p = 0.049). The NRS upon discharge, as well as the McGill and PSQI scores at the time of discharge and at 1, 3, 6 and 12 months post-discharge, were all significantly reduced compared to those measured upon admission in two groups (p = 0.000). Conclusion: Gasserian ganglion PRF therapy combined with low-dose morphine injection offers an alternative option for managing intractable herpetic neuralgia and prevention of postherpetic neuralgia in ocular branches. Clinical Trial Registration: ChiCTR2300073281.

Childhood sexual trauma and opioid use among older adults living with HIV.

Childhood sexual abuse (CSA) has been linked to substance use and substance use disorders in adulthood. However, there have been limited studies examining the relationship between CSA and opioid use among older adults living with HIV (OALH). Therefore, the aim of this study was to determine the association between CSA and opioid use among OALH (n = 91). Data were obtained from an HIV clinic population in South Carolina using paper-and-pen, and online questionnaires. CSA was operationalized using six questions from the Early Trauma Inventory-Self Report Form (Yes vs. No). Opioid use was self-report of the use of opioids including: heroin, fentanyl, Oxycontin, Vicodin, codeine, morphine (used vs. never used). Nested crude and multivariable logistic regression models adjusting for sociodemographic confounders were used to determine the association between CSA and opioid use. After adjusting for race, gender, age, and education, OALH who were CSA survivors were 21 times more likely to currently use opioids compared to OALH who were not exposed to CSA (adjusted OR: 21.1; 95% CI: 1.78-250.0). The association seen between CSA history and opioid use may be due to unresolved trauma among OALH. Trauma-informed interventions addressing CSA may help to reduce opioid use among OALH.