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Background: Despite proliferation of acute-care interventions to initiate medications for opioid use disorder (MOUD), significant challenges remain to supporting care continuity following discharge. Research is needed to inform effective hospital strategies to support patient transitions to ongoing MOUD in the community., Objective: To inform a taxonomy of care transition strategies to support MOUD continuity from hospital to community-based settings and assess their perceived impact and feasibility among experts in the field., Design: A modified Delphi consensus process through three rounds of electronic surveys., Participants: Experts in hospital-based opioid use disorder (OUD) treatment, care transitions, and hospital-based addiction treatment., Main Measures: Delphi participants rated the impact and feasibility of 14 OUD care transition strategies derived from a review of the scientific literature on a scale from 1 to 9 over three survey rounds. Panelists were invited to suggest additional care transition strategies. Agreement level was calculated based on proportion of ratings within three points of the median., Key Results: Forty-five of 71 invited panelists participated in the survey. Agreement on impact was strong for 12 items and moderate for 10. Agreement on feasibility was strong for 11 items, moderate for 7, and poor for 4. Strategies with highest ratings on impact and feasibility included initiation of MOUD in-hospital and provision of buprenorphine prescriptions or medications before discharge. All original 14 strategies and 8 additional strategies proposed by panelists were considered medium- or high-impact and were incorporated into a final taxonomy of 22 OUD care transition strategies., Conclusions: Our study established expert consensus on impactful and feasible hospital strategies to support OUD care transitions from the hospital to community-based MOUD treatment, an area with little empirical research thus far. It is the hope that this taxonomy serves as a stepping-stone for future evaluations and clinical practice implementation toward improved MOUD continuity and health outcomes., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Competing Interests: Conflicts of interest None disclosed.

Background: Offering medications for opioid use disorder (MOUD) in carceral settings significantly reduces overdose. However, it is unknown to what extent individuals in jails continue MOUD once they leave incarceration. We aimed to assess the relationship between in-jail MOUD and MOUD continuity in the month following release., Methods: We conducted a retrospective cohort study of linked NYC jail-based electronic health records and community Medicaid OUD treatment claims for individuals with OUD discharged from jail between 2011 and 2017. We compared receipt of MOUD within 30 days of release, among those with and without MOUD at release from jail. We tested for effect modification based on MOUD receipt prior to incarceration and assessed factors associated with treatment discontinuation., Results: Of 28,298 eligible incarcerations, 52.8 % received MOUD at release. 30 % of incarcerations with MOUD at release received community-based MOUD within 30 days, compared to 7 % of incarcerations without MOUD (Risk Ratio: 2.62 (2.44-2.82)). Most (69 %) with MOUD claims prior to incarceration who received in-jail MOUD continued treatment in the community, compared to 9 % of those without prior MOUD. Those who received methadone (vs. buprenorphine), were younger, Non-Hispanic Black and with no history of MOUD were less likely to continue MOUD following release., Conclusions: MOUD maintenance in jail is strongly associated with MOUD continuity upon release. Still, findings highlight a gap in treatment continuity upon-reentry, especially among those who initiate MOUD in jail. In the wake of worsening overdose deaths and troubling disparities, improving MOUD continuity among this population remains an urgent priority., Competing Interests: Declaration of Competing Interest Dr. Murphy served on an advisory board panel for Indivior, outside the submitted work. Dr. Krawczyk receives compensation for expert testimony for ongoing opioid litigation. All other authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

The high overdose mortality rates in the United States poses several questions: Why have they been increasing exponentially since 1979? Why are they so high? And how can they be greatly reduced? Building on past research, the causes of the increase seem to be deeply rooted in US social and economic structures and processes, rather than due only to opioid prescription patterns or the advent of synthetic opioids. Given this, we consider what changes might be needed to reverse the exponentially-increasing overdose mortality. We use a path dependency argument to argue that the United States political, economic, and public health systems have helped create this crisis and, unfortunately, continue to heighten it. These same systems suggest that proposals to expand harm reduction and drug treatment capacity, to decriminalize or legalize drugs, or to re-industrialize the country sufficiently to reduce "communities of despair" will not be enacted at a scale sufficient to end the overdose crisis. We thus suggest that in the United States serious improvements in overdose rates and related policies and structures require massive social movements with a broad social change agenda., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Hospitals are an ideal setting to stage opioid-related interventions with patients who are hospitalized due to overdose or other substance use-related complications. Transitional opioid programs-which initiate care and provide linkages upon discharge, such as screening, initiation of medications for opioid use disorder, and addiction consult services-have become the gold standard, but implementation has been uneven. The purpose of this study was to assess disparities in the availability of hospital-based transitional opioid programs, across rural and urban hospital settings in the United States., Methods: Using hospital administrative data paired with county-level demographic data, we conducted bivariate and regression analyses to assess rural-urban differences in the availability of transitional opioid services including screening, addiction consult services, and MOUD in U.S general medical centers, controlling for hospital- and community-level factors. Our sample included 2846 general medical hospitals that completed the 2021 American Hospital Association (AHA) Annual Survey of Hospitals. Our primary outcomes were five self-reported measures: whether the hospital provided screening in the ED; provided screening in the inpatient setting; whether the hospital provided addiction consult services in the ED; provided addiction consult services in the inpatient setting; and whether the hospital provided medications for opioid use disorder., Results: Rural hospitals did not have lower odds of screening for OUD or other SUDs than urban hospitals, but both micropolitan rural counties and noncore rural counties had significantly lower odds of having addiction consult services in either the ED (OR: 0.74, 95 % CI: 0.58, 0.95; OR: 0.68, 95 % CI: 0.50, 0.91) or inpatient setting (OR: 0.76, 95 % CI: 0.59, 0.97; OR: 0.68, 95 % CI: 0.50, 0.93), respectively, or of offering MOUD (OR: 0.69, 95 % CI: 0.52, 0.90; OR: 0.52, 95 % CI: 0.37, 0.74)., Conclusions: Our study suggests that evidence-based interventions, such as medications for opioid use disorder and addiction consult services, are less often available in rural hospitals, which may contribute to rural-urban disparities in health outcomes secondary to OUD. A priority for population health improvement should be developing implementation strategies to support rural hospital adoption of transitional opioid programs., Competing Interests: Declaration of competing interest None of the authors have conflicts of interest to report., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Hospitals are a key touchpoint to reach patients with substance use disorders (SUDs) and link them with ongoing community-based services. Although there are many acute care interventions to initiate SUD treatment in hospital settings, less is known about what services are offered to transition patients to ongoing care after discharge. In this study, we explore what SUD care transition strategies are offered across nonprofit US hospitals., Methods: We analyzed administrative documents from a national sample of US hospitals that indicated SUD as a top 5 significant community need in their Community Health Needs Assessment reports (2019-2021). Data were coded and categorized based on the nature of described services. We used data on hospitals and characteristics of surrounding counties to identify factors associated with hospitals' endorsement of transition interventions for SUD., Results: Of 613 included hospitals, 313 prioritized SUD as a significant community need. Fifty-three of these hospitals (17%) offered acute care interventions to support patients' transition to community-based SUD services. Most (68%) of the 53 hospitals described transition strategies without further detail, 23% described scheduling appointments before discharge, and 11% described discussing treatment options before discharge. No hospital characteristics were associated with offering transition interventions, but such hospitals were more likely to be in the Northeast, in counties with higher median income, and states that expanded Medicaid., Conclusions: Despite high need, most US hospitals are not offering interventions to link patients with SUD from acute to community care. Efforts to increase acute care interventions for SUD should identify and implement best practices to support care continuity., Competing Interests: NK provides expert testimony for ongoing opioid litigation. The remaining authors report no conflicts of interest., (Copyright © 2023 American Society of Addiction Medicine.)

Background: Black and Latinx populations are disproportionately affected by stroke and are likely to experience gaps in health care. Within fragmented care systems, remote digital solutions hold promise in reversing this pattern. However, there is a digital divide that follows historical disparities in health. Without deliberate attempts to address this digital divide, rapid advances in digital health will only perpetuate systemic biases. This study aimed to characterize the range of digital health interventions for stroke care, summarize their efficacy, and examine the inclusion of Black and Latinx populations in the evidence base., Methods: We searched PubMed, the Web of Science, and EMBASE for publications between 2015 and 2021. Inclusion criteria include peer-reviewed systematic reviews or meta-analyses of experimental studies focusing on the impact of digital health interventions on stroke risk factors and outcomes in adults. Detailed information was extracted on intervention modality and functionality, clinical/behavioral outcome, study location, sample demographics, and intervention results., Results: Thirty-eight systematic reviews met inclusion criteria and yielded 519 individual studies. We identified six functional categories and eight digital health modalities. Case management (63%) and health monitoring (50%) were the most common intervention functionalities. Mobile apps and web-based interventions were the two most commonly studied modalities. Evidence of efficacy was strongest for web-based, text-messaging, and phone-based approaches. Although mobile applications have been widely studied, the evidence on efficacy is mixed. Blood pressure and medication adherence were the most commonly studied outcomes. However, evidence on the efficacy of the various intervention modalities on these outcomes was variable. Among all individual studies, only 38.0% were conducted in the United States (n = 197). Of these U.S. studies, 54.8% adequately reported racial or ethnic group distribution. On average, samples were 27.0% Black, 17.1% Latinx, and 63.4% White., Conclusion: While evidence of the efficacy of selected digital health interventions, particularly those designed to improve blood pressure management and medication adherence, show promise, evidence of how these interventions can be generalized to historically underrepresented groups is insufficient. Including these underrepresented populations in both digital health experimental and feasibility studies is critical to advancing digital health science and achieving health equity., (© 2023. The Author(s).)

Importance: Two states modified laws to remove or substantially reduce criminal penalties for any drug possession. The hypothesis was that removing criminal penalties for drug possession may reduce fatal drug overdoses due to reduced incarceration and increased calls for help at the scene of an overdose., Objective: To evaluate whether decriminalization of drug possession in Oregon and Washington was associated with changes in either direction in fatal drug overdose rates., Design, Setting, and Participants: This cohort study used a synthetic control method approach to examine whether there were changes in drug possession laws and fatal drug overdose rates in Oregon and Washington in the postpolicy period (February 1, 2021, to March 31, 2022, in Oregon and March 1, 2021, to March 31, 2022, in Washington). A counterfactual comparison group (synthetic controls) was created for Oregon and Washington, using 48 states and the District of Columbia, that did not implement similar policies during the study period (January 1, 2018, to March 31, 2022). For 2018-2021, final multiple cause-of-death data from the National Vital Statistics System (NVSS) were used. For 2022, provisional NVSS data were used. Drug overdose deaths were identified using International Statistical Classification of Diseases and Related Health Problems, 10th Revision underlying cause-of-death codes X40-X44, X60-X64, X85, and Y10-Y14., Exposures: In Oregon, Measure 110 went into effect on February 1, 2021. In Washington, the Washington Supreme Court decision in State v Blake occurred on February 25, 2021., Main Outcome: Monthly fatal drug overdose rates., Results: Following the implementation of Measure 110, absolute monthly rate differences between Oregon and its synthetic control were not statistically significant (probability = 0.26). The average rate difference post Measure 110 was 0.268 fatal drug overdoses per 100 000 state population. Following the implementation of the policy change in Washington, the absolute monthly rate differences between Washington and synthetic Washington were not statistically significant (probability = 0.06). The average rate difference post Blake was 0.112 fatal drug overdoses per 100 000 state population., Conclusions and Relevance: This study found no evidence of an association between legal changes that removed or substantially reduced criminal penalties for drug possession in Oregon and Washington and fatal drug overdose rates. Additional research could examine potential other outcomes as well as longer-term associations with fatal drug overdose overall and across racial and ethnic groups.

Background: Acute-care interventions that identify patients with substance use disorders (SUDs), initiate treatment, and link patients to community-based services, have proliferated in recent years. Yet, much is unknown about the specific strategies being used to support continuity of care from emergency department (ED) or inpatient hospital settings to community-based SUD treatment. In this scoping review, we synthesize the existing literature on patient transition interventions, and form an initial typology of reported strategies., Methods: We searched Pubmed, Embase, CINAHL and PsychINFO for peer-reviewed articles published between 2000 and 2021 that studied interventions linking patients with SUD from ED or inpatient hospital settings to community-based SUD services. Eligible articles measured at least one post-discharge treatment outcome and included a description of the strategy used to promote linkage to community care. Detailed information was extracted on the components of the transition strategies and a thematic coding process was used to categorize strategies into a typology based on shared characteristics. Facilitators and barriers to transitions of care were synthesized using the Consolidated Framework for Implementation Research., Results: Forty-five articles met inclusion criteria. 62% included ED interventions and 44% inpatient interventions. The majority focused on patients with opioid (71%) or alcohol (31%) use disorder. The transition strategies reported across studies were heterogeneous and often not well described. An initial typology of ten transition strategies, including five pre- and five post-discharge transition strategies is proposed. The most common strategy was scheduling an appointment with a community-based treatment provider prior to discharge. A range of facilitators and barriers were described, which can inform efforts to improve hospital-to-community transitions of care., Conclusions: Strategies to support transitions from acute-care to community-based SUD services, although critical for ensuring continuity of care, vary greatly across interventions and are inconsistently measured and described. More research is needed to classify SUD care transition strategies, understand their components, and explore which lead to the best patient outcomes., (© 2023. The Author(s).)

Background: Despite evidence that the U.S. "War on Drugs" is associated with increases in drug-related harm and other negative outcomes, all U.S. states have long criminalized most drug possession. In early 2021, both Oregon and Washington became exceptions to this rule when they fully (Oregon) or partially (Washington) decriminalized possession of small amounts of all drugs., Methods: We obtained arrest data for 2019 to 2021 for intervention states (Oregon and Washington) and control states (Colorado, Idaho, Montana, and Nevada). We calculated monthly rates for arrests overall and for violent crimes, drug possession, equipment possession, non-drug crimes, and a set of low-level crimes termed displaced arrests. Using an interrupted time series analysis, we examined changes in monthly arrest rates after the implementation of policy change in Oregon and Washington compared to control states., Results: In Oregon, there were 3 fewer drug possession arrests per 100,000 in the month after the policy change; the rate decreased throughout the post-implementation period. In Washington, there were almost 5 fewer drug possession arrests per 100,000 in the month following policy change, and the rate remained stable thereafter. Both declines were significantly greater than in comparison states. There were also statistically significant reductions in arrests for possession of drug equipment in Washington and a significant increase in displaced arrests in Oregon. There were no significant changes in overall arrests, non-drug arrests or arrests for violent crime in either state, relative to controls., Conclusion: This analysis demonstrates that it is possible for state drug decriminalization policies to dramatically reduce arrests for drug possession without increasing arrests for violent crimes, potentially reducing harm to people who use drugs and their communities. Additional research is needed to determine whether these legal reforms were associated with changes in overdose rates and other drug-related harms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Substance use disorders (SUD) are associated with increased risk of worse COVID-19 outcomes. Likewise, racial/ethnic minority patients experience greater risk of severe COVID-19 disease compared to white patients. Providers should understand the role of race and ethnicity as an effect modifier on COVID-19 severity among individuals with SUD. This retrospective cohort study assessed patient race/ethnicity as an effect modifier of the risk of severe COVID-19 disease among patients with histories of SUD and overdose. We used merged electronic health record data from 116,471 adult patients with a COVID-19 encounter between March 2020 and February 2021 across five healthcare systems in New York City. Exposures were patient histories of SUD and overdose. Outcomes were risk of COVID-19 hospitalization and subsequent COVID-19-related ventilation, acute kidney failure, sepsis, and mortality. Risk factors included patient age, sex, and race/ethnicity, as well as medical comorbidities associated with COVID-19 severity. We tested for interaction between SUD and patient race/ethnicity on COVID-19 outcomes. Findings showed that Non-Hispanic Black, Hispanic/Latino, and Asian/Pacific Islander patients experienced a higher prevalence of all adverse COVID-19 outcomes compared to non-Hispanic white patients. Past-year alcohol (OR 1.24 [1.01-1.53]) and opioid use disorders (OR 1.91 [1.46-2.49]), as well as overdose history (OR 4.45 [3.62-5.46]), were predictive of COVID-19 mortality, as well as other adverse COVID-19 outcomes. Among patients with SUD, significant differences in outcome risk were detected between patients of different race/ethnicity groups. Findings indicate that providers should consider multiple dimensions of vulnerability to adequately manage COVID-19 disease among populations with SUDs., Competing Interests: Declaration of Competing Interest Dr. Levin receives research support from Aelis Pharma and medication from Indivior for research and royalties from APA publishing. In addition, she served as a nonpaid member of a Scientific Advisory Board for Alkermes, Indivior, Novartis, Teva, and US WorldMeds and is a consultant to Major League Baseball. Dr. Krawczyk is involved in ongoing opioid litigation. Dr. Pincus has served on clinical advisory committees for AbleTo, Cerebral, Magellan Studio, and Eleos. All other authors report no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Buprenorphine is a highly effective treatment for opioid use disorder (OUD) and a critical tool for addressing the worsening US overdose crisis. However, multiple barriers to treatment-including stringent federal regulations-have historically made this medication hard to reach for many who need it. In 2020, under the COVID-19 public health emergency, federal regulators substantially changed access to buprenorphine by allowing prescribers to initiate patients on buprenorphine via telehealth without first evaluating them in person. As the public health emergency has been set to expire in May of 2023, Congress and federal agencies can leverage extensive evidence from studies conducted during the wake of the pandemic to make evidence-based decisions on the regulation of buprenorphine going forward. To aid policy makers, this narrative review synthesizes and interprets peer-reviewed research on the effect of buprenorphine flexibilities on the uptake and implementation of telehealth, and its impact on OUD patient and prescriber experiences, access to treatment, and health outcomes. Overall, our review finds that many prescribers and patients took advantage of telehealth, including the audio-only option, with a wide range of benefits and few downsides. As a result, federal regulators-including agencies and Congress-should continue nonrestricted use of telehealth for buprenorphine initiation., Competing Interests: Conflicts of interest Please see ICMJE form(s) for author conflicts of interest. These have been provided as supplementary materials., (© The Author(s) 2023. Published by Oxford University Press on behalf of Project HOPE - The People-To-People Health Foundation, Inc.)

Pre-existing mental disorders are linked to COVID-19-related outcomes. However, the findings are inconsistent and a thorough analysis of a broader spectrum of outcomes such as COVID-19 infection severity, morbidity, and mortality is required. We investigated whether the presence of psychiatric diagnoses and/or the use of antidepressants influenced the severity of the outcome of COVID-19. This retrospective cohort study evaluated electronic health records from the INSIGHT Clinical Research Network in 116,498 individuals who were diagnosed with COVID-19 between March 1, 2020, and February 23, 2021. We examined hospitalization, intubation/mechanical ventilation, acute kidney failure, severe sepsis, and death as COVID-19-related outcomes. After using propensity score matching to control for demographics and medical comorbidities, we used contingency tables to assess whether patients with (1) a history of psychiatric disorders were at higher risk of more severe COVID-19-related outcomes and (2) if use of antidepressants decreased the risk of more severe COVID-19 infection. Pre-existing psychiatric disorders were associated with an increased risk for hospitalization, and subsequent outcomes such as acute kidney failure and severe sepsis, including an increased risk of death in patients with schizophrenia spectrum disorders or bipolar disorders. The use of antidepressants was associated with significantly reduced risk of sepsis (p = 0.033), death (p = 0.026). Psychiatric disorder diagnosis prior to a COVID-19-related healthcare encounter increased the risk of more severe COVID-19-related outcomes as well as subsequent health complications. However, there are indications that the use of antidepressants might decrease this risk. This may have significant implications for the treatment and prognosis of patients with COVID-19., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Aims: Individuals with opioid use disorder (OUD) suffer disproportionately from COVID-19. To inform clinical management of OUD patients, research is needed to identify characteristics associated with COVID-19 progression and death among this population. We aimed to investigate the role of OUD and specific comorbidities on COVID-19 progression among hospitalized OUD patients., Design: Retrospective cohort study of merged electronic health records (EHR) from five large private health systems., Setting: New York City, New York, USA, 2011-21., Participants: Adults with a COVID-19 encounter and OUD or opioid overdose diagnosis between March 2020 and February 2021., Measurements: Primary exposure included diagnosis of OUD/opioid overdose. Risk factors included age, sex, race/ethnicity and common medical, substance use and psychiatric comorbidities known to be associated with COVID-19 severity. Outcomes included COVID-19 hospitalization and subsequent intubation, acute kidney failure, severe sepsis and death., Findings: Of 110 917 COVID-19+ adults, 1.17% were ever diagnosed with OUD/opioid overdose. OUD patients had higher risk of COVID-19 hospitalization [adjusted risk ratio (aRR) = 1.40, 95% confidence interval (CI) = 1.33, 1.47], intubation [adjusted odds ratio (aOR) = 2.05, 95% CI = 1.74, 2.42], kidney failure (aRR = 1.51, 95% CI = 1.34, 1.70), sepsis (aRR = 2.30, 95% CI = 1.88, 2.81) and death (aRR = 2.10, 95% CI = 1.84, 2.40). Among hospitalized OUD patients, risks for worse COVID-19 outcomes included being male; older; of a race/ethnicity other than white, black or Hispanic; and having comorbid chronic kidney disease, diabetes, obesity or cancer. Protective factors included having asthma, hepatitis-C and chronic pain., Conclusions: Opioid use disorder patients appear to have a substantial risk for COVID-19-associated morbidity and mortality, with particular comorbidities and treatments moderating this risk., (© 2022 Society for the Study of Addiction.)

As the USA faces a worsening overdose crisis, improving access to evidence-based treatment for opioid use disorder (OUD) remains a policy priority. Federal regulatory changes in response to the COVID-19 pandemic substantially expanded flexibilities on take-home doses for methadone treatment for OUD. These changes have fuelled questions about the effect of new regulations on OUD outcomes and the potential effect on health of permanently integrating these flexibilities into treatment policy going forward. To aide US policy makers as they consider implementing permanent methadone regulatory changes, we conducted a review synthesising peer-reviewed research on the effect of the flexibilities of methadone take-home policies introduced during COVID-19 on methadone programme operations, OUD patient and provider experiences, and patient health outcomes. We interpret the findings in the context of the federal rule-making process and discuss avenues by which these findings can be incorporated and implemented into US policies on substance use treatment going forward., Competing Interests: Declaration of interests NK declares providing expert testimony in an ongoing opioid litigation. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The United States overdose crisis continues unabated. Despite efforts to increase capacity for treating opioid use disorder (OUD) in the U.S., how actual treatment receipt compares to need remains unclear. In this cross-sectional study, we estimate progress in addressing the gap between OUD prevalence and OUD treatment receipt at the national and state levels from 2010 to 2019., Methods: We estimated past-year OUD prevalence rates based on the U.S. National Survey on Drug Use and Health (NSDUH), using adjustment methods that attempt to account for OUD underestimation in national household surveys. We used data from specialty substance use treatment records and outpatient pharmacy claims to estimate the gap between OUD prevalence and number of persons receiving medications for opioid use disorder (MOUD) during the past decade., Results: Adjusted estimates suggest past-year OUD affected 7,631,804 individuals in the U.S. in (2,773 per 100,000 adults 12+), relative to only 1,023,959 individuals who received MOUD (365 per 100,000 adults 12+). This implies approximately 86.6% of individuals with OUD nationwide who may benefit from MOUD treatment do not receive it. MOUD receipt increased across states over the past decade, but most regions still experience wide gaps between OUD prevalence and MOUD receipt., Conclusions: Despite some progress in expanding access to MOUD, a substantial gap between OUD prevalence and treatment receipt highlights the critical need to increase access to evidence-based services., Competing Interests: Declaration of interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Keyes reports personal fees for consultation and testimony in litigation., (Copyright © 2022. Published by Elsevier B.V.)

The protease activated receptor (PAR) family is a group of G-protein coupled receptors (GPCRs) activated by proteolytic cleavage of the extracellular domain. PARs are expressed in a variety of cell types with crucial roles in homeostasis, immune responses, inflammation, and pain. PAR3 is the least researched of the four PARs, with little known about its expression and function. We sought to better understand its potential function in the peripheral sensory nervous system. Mouse single-cell RNA sequencing data demonstrates that PAR3 is widely expressed in dorsal root ganglion (DRG) neurons. Co-expression of PAR3 mRNA with other PARs was identified in various DRG neuron subpopulations, consistent with its proposed role as a coreceptor of other PARs. We developed a lipid tethered PAR3 agonist, C660, that selectively activates PAR3 by eliciting a Ca 2+ response in DRG and trigeminal neurons. In vivo, C660 induces mechanical hypersensitivity and facial grimacing in WT but not PAR3 -/- mice. We characterized other nociceptive phenotypes in PAR3 -/- mice and found a loss of hyperalgesic priming in response to IL-6, carrageenan, and a PAR2 agonist, suggesting that PAR3 contributes to long-lasting nociceptor plasticity in some contexts. To examine the potential role of PAR3 in regulating the activity of other PARs in sensory neurons, we administered PAR1, PAR2, and PAR4 agonists and assessed mechanical and affective pain behaviors in WT and PAR3 -/- mice. We observed that the nociceptive effects of PAR1 agonists were potentiated in the absence of PAR3. Our findings suggest a complex role of PAR3 in the physiology and plasticity of nociceptors. PERSPECTIVE: We evaluated the role of PAR3, a G-protein coupled receptor, in nociception by developing a selective peptide agonist. Our findings suggest that PAR3 contributes to nociception in various contexts and plays a role in modulating the activity of other PARs., (Copyright © 2021 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)