Browsing by Subject "Opioid"

Opioid drug abuse represents a serious public health concern with few effective therapeutic strategies. A primary goal for researchers modeling substance abuse disorders has been the delineation of the biological and environmental factors that shape an individual’s susceptibility or resistance to the reinforcing properties of abused substances. Early-life environmental conditions are frequently implicated as critical mediators for later-life health outcomes, although the cellular and molecular mechanisms that underlie these effects have historically been challenging to identify. Previous work has shown that a neonatal handling procedure in rats (which promotes enriched maternal care) attenuates morphine conditioning, reduces morphine-induced glial activation in the nucleus accumbens (NAc), and increases microglial expression of the anti-inflammatory cytokine interleukin-10 (IL-10). The experiments described in this dissertation were thus designed to address if inflammatory signaling in the NAc may underlie the effects of early-life experience on later-life opioid drug-taking. The results demonstrate that neonatal handling attenuates intravenous self-administration of the opioid remifentanil in a drug concentration-dependent manner. Transcriptional profiling of the NAc reveals a suppression of pro-inflammatory cytokine and chemokine signaling molecules and an increase in anti-inflammatory IL-10 in handled rats following repeated exposure to remifentanil. To directly test the hypothesis that anti-inflammatory signaling can alter drug-taking behavior, bilateral intracranial injections of plasmid DNA encoding IL-10 (pDNA-IL-10) or control pDNA were delivered into the NAc of naïve rats. pDNA-IL-10 treatment reduces remifentanil self-administration in a drug concentration-dependent manner, similar to the previous observations in handled rats. Additional experiments confirmed that neither handling nor pDNA-IL-10 treatment alters operant responding for food or sucrose rewards. These results help define the conditions under which ventral striatal neuroimmune signaling may influence motivated behaviors for highly reinforcing opioid drugs.

Background

Methods

Results

Conclusions

Level of evidence

Chronic pain impacts 100 million adult Americans in their lifetime, comprises the third-highest category of all health spending, and is responsible for up to 20% of primary care visits. Chronic pain treatment guidelines: recommend a biopsychosocial, multimodal management approach that addresses the physical and mental aspects of chronic pain. Nurse practitioners (NPs) have a unique role to play in chronic pain, due to their biopsychosocial training in chronic disease management in primary care that aligns well with this recommended approach. However, little is known about how NPs manage chronic pain or factors that influence those patterns. These gaps have implications on NP regulation and workforce development, as well as primary care transformation and clinical practice. Therefore, the purpose of this dissertation is to understand primary care NPs’ opioid and non-opioid prescribing patterns and the patient, provider, and system-level factors that influence those patterns.This dissertation includes a scoping review in Chapter 2 that demonstrates the negative impact of NP regulatory restrictions on patient access to chronic pain care, as well as treatment for OUD. Chapter 3 features a systematic review that examines primary care chronic pain prescribing patterns among physicians, NPs, and physician assistants (PA). This chapter highlights the lack of literature on NP and PA prescribing patterns specific to primary care, as well as the lack of prescribing pattern literature on non-opioid and non-pharmacologic modalities, despite the recommendations of these therapies in multiple national chronic pain guidelines. Chapter 4 presents the findings of a 31-item survey, developed by the authors, of 128 NPs from across the U.S. This survey examined the challenges and experiences of NPs who manage chronic pain and analyzed the impact of those experiences on the frequency with which NPs prescribe various pharmacologic and non-pharmacologic pain therapies. Findings indicate that NPs strongly identified with a variety of chronic pain management challenges, including patient access and insurance coverage of non-pharmacologic care, regulatory restrictions, and concerns of misuse. Additionally, NP-level factors such as setting of practice and education level significantly impacted NPs’ prescribing patterns and their perception of difficulty in managing chronic pain. Finally, Chapter 5 utilized a national VA dataset, including 39,936 12-month summary records between patients and their primary care providers, to compare opioid and non-opioid prescribing patterns of physicians, NPs, and PAs. After adjusting for patient factors, physicians had the highest odds of prescribing opioids and non-opioids compared to NPs and PAs. However, very small effect sizes may indicate that these differences do not hold significant clinical meaning. Patient factors, such as race/ethnicity, gender, age, level of education, number of comorbidities, number of chronic pain diagnoses, and self-reported health and mental health statuses, influenced prescription of opioid and non-opioid medications after adjusting for all other variables. Chronic pain is an exemplar of necessary primary care transformation priorities, including primary and behavioral health integration, value-based payment and delivery, team-based and well-coordinated care, and promotion accessible, equitable care. NPs are well-suited to address the complex needs of chronic pain patients. The findings of this dissertation indicate that NPs are slightly less likely than physicians to prescribe opioids and non-opioids; however, patient characteristics may increase the odds of a medication prescription more so than provider type. Furthermore, these findings identify patient, provider, and system-level challenges that NPs experience while managing chronic pain. The findings of this dissertation may contribute to important advancements in policy, practice, education, and research.