Medicine and Health Sciences Commons^™

Opioid System's Involvement In Ketamine's Antidepressant-Like Effects, Fan Zhang

Theses and Dissertations

Depression is one of the most debilitating disorders in the world. The currently available medications typically have a 2-4 week delay in their therapeutic effects and are ineffective for about 40% of patients. In 2000, a subanesthetic dose (0.5 mg/kg i.e.) of the dissociative anesthetic ketamine was reported to have both rapid and robust antidepressant effects in in treatment-resistant depressed patients. However, the mechanisms responsible for ketamine’s antidepressant effects remain unclear. In 2018, a clinical study reported that pretreatment with the nonselective opioid antagonist naltrexone attenuated the rapid antidepressant effect of ketamine in depressed patients. The current study investigated the …

Prescription Drug Monitoring Programs And Opioid Poisoning: Evaluating The Impact Of Prescriber Use Mandates On Prescription Opioid Poisoning Emergency Department Visits, Sarah Almanie

Theses and Dissertations

Introduction: Prescription drug monitoring programs (PDMPs) are one strategy established to curb the prescription opioid abuse epidemic. Prescriber use mandates has emerged as a promising practice to increase PDMPs impact on prescription opioid abuse; however, evidence of its effectiveness has not yet been established. Kentucky was the first state to implement comprehensive prescriber use mandates in July 2012.

Objective: To assess the relationship between prescriber use mandates policy and emergency department (ED) visits related to prescription opioid poisoning among adults in Kentucky and

North Carolina. Secondary aim: to evaluate the economic impact of prescriber use mandates in Kentucky.

Methods: A …

Gastrointestinal Microbiota Modulate Antinociceptive Tolerance Development In Mice With Chronic Morphine Exposure, Ryan A. Mischel

Theses and Dissertations

In October 2017, the United States government declared a state of public health emergency in response to the burgeoning prescription opioid epidemic. Opioid analgesics are the gold standard of therapy for moderate to severe pain, but their clinical utility is greatly limited by analgesic tolerance – a primary driver of diminished pain control and opioid dose escalations. Integral in this process are primary afferent sensory neurons in dorsal root ganglia (DRG), the first-order components of nociceptive sensation. With surmounting evidence that morphine and other narcotics can alter gut microbial composition and promote bacterial translocation to other tissues, a question arises …

Effects Of Chemotherapy On Motivated Behavior And Opioid Reward In Rats, Luke P. Legakis

Theses and Dissertations

Paclitaxel, vincristine, oxaliplatin, and bortezomib are cancer chemotherapy drugs with adverse effects that include chemotherapy-induced neuropathic pain (CINP) as well as depression of behavior and mood. In the clinical setting, opioids are often used concurrently with or following chemotherapy to treat pain related to the cancer or CINP, but repeated opioid exposure can also increase the risk of opioid abuse. This dissertation evaluated the effect of chemotherapy treatment on motivated behaviors and opioid reward in rats. The main findings of this evaluation are as follows: (1) Chemotherapy, at doses that produce robust and sustained mechanical hypersensitivity produce only weak or …

Chronic Pain Causal Attributions In An Interdisciplinary Primary Care Clinic: Patient-Provider And Provider-Provider Discrepancies, Bryan Jensen

Theses and Dissertations

The purpose of the present study was to investigate the influence of pain causal attributions on patient pain-related functioning, treatment engagement, and clinical outcomes. Additionally, the impact of discordant pain causal attributions between patients and their providers as well as between interdisciplinary providers was examined. Patients rated their pain functioning and causal pain attributions during a regular clinic visit. Following the patient’s visit both the behavioral medicine provider and internal medicine resident provided ratings of similar pain-related functioning domains and causal attributions. Follow-up data were collected from the electronic medical record three months following that clinic visit. Overall, results revealed …

Development And Evaluation Of The Assessment Of Opioid Taking Behaviors And Adherence Scale (Aotba) In Patients With Sickle Cell Disease, Abdulkhaliq Jassem Alsalman

Theses and Dissertations

The rapid growth in opioid therapy for non-cancer pain has occurred without an adequate appreciation of the consequences of this growth. Few studies provide patient-centered evidence that can be used to inform the current proposed standards for efficacious (safe and effective) opioid prescribing in non-cancer pain. Furthermore, different terms may be used interchangeably in the literature to refer to opioid-taking behaviors, resulting in imprecise or vague interpretation of existing evidence. We therefore sought to explore patterns of opioid-taking behavior and their biopsychosocial-spiritual determinants in African-American adults with sickle cell disease (SCD). Many questions surround opioid use for non-cancer pain, but …

Development Of Antagonists Targeting Chemokine Receptor Ccr5 And The Chemokine Receptor Ccr5 – Mu Opioid Receptor Heterodimer, Christopher Kent Arnatt

Theses and Dissertations

The chemokine receptor CCR5 (CCR5) plays an integral role within the inflammatory network of cells. Importantly, CCR5 is a mediator in several disease states and can be targeted using small molecule antagonists. Within this work, CCR5’s role in prostate cancer and HIV/AIDS has been exploited in order to develop potential therapeutics and probes. First, a series of novel compounds was designed by using pharmacophore-based drug design based upon known CCR5 antagonists and molecular modeling studies of the CCR5 receptor’s three-dimensional conformation. Once synthesized, these compounds were tested for their CCR5 antagonism and their anti-proliferative effects in several prostate cancer cell …

The Economic Burden Of Opioid Poisoning In The United States And Determinants Of Increased Costs In Opioid Poisoning, Timothy Inocencio

Theses and Dissertations

Introduction: Opioid poisoning has been rapidly increasing in the past decade, and has been driven in large part due to increases in opioid prescribing. This has been accompanied by intervention efforts aimed at preventing and reversing opioid poisoning through naloxone prescription programs. Current literature have not quantified the economic burden of opioid poisoning. Understanding this information can help inform these efforts and bring light to this growing problem. In addition understanding various determinants of increased costs can help to identify the types of populations more likely to have greater costs. Main Objectives: The objectives are 1) to quantify the economic …

Enzymatic Regulation Of Opioid Antinociception And Tolerance, Lynn Hull

Theses and Dissertations

ENZYMATIC REGULATION OF OPIOID ANTINOCICEPTION AND TOLERANCE By Lynn C. Hull, Ph.D. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2009 Director: William L. Dewey, Ph.D. Department of Pharmacology and Toxicology The involvement of kinases in opioid actions has long been established. The acute actions of opioids, through the Gi/Go G-proteins, cause the inhibition of adenylyl cyclase and therefore a decrease in protein kinase A (PKA) activation. Additionally, acute opioid administration may cause the G-protein to activate the phospholipase C (PLC)-mediated cascade leading to the …

The Effect Of Chronic Constriction Injury On Cellular Systems Within Nociceptive Pathways In The Mouse, Michelle Hoot

Theses and Dissertations

Chronic neuropathic pain is often difficult to treat due to its resistance to therapeutic intervention. This is due in part to the poor understanding of the physiological mechanisms involved in the establishment and maintenance of neuropathic pain states. The neuropathic pain model, chronic constriction injury of the sciatic nerve, produced robust pain hypersensitivity in our mice. It also induced significant changes in the mitogen activated protein kinase family, and the cannabinoid and µ-opioid systems in three different brain areas involved in the modulation or regulation of pain states. CCI induced a 2.5 fold increase in mRNA of the kinase Raf-1 …

The Study Of The Effect Of Drugs Of Abuse On Protein Kinase A Activity In Mouse Brain And Spinal Cord, George D. Dalton

Theses and Dissertations

Morphine and Δ9-THC are drugs that produce analgesia and rewarding effects. However, chronic treatment with morphine and Δ9-THC produces problematic side-effects including tolerance and physical dependence. The cellular mechanisms underlying opioid and cannabinoid antinociceptive tolerance have been studied for years. Research has demonstrated that the expression of morphine and Δ9-THC antinociceptive tolerance may be mediated through intracellular signaling pathways, such as the adenylyl cyclase /Protein Kinase A (PKA) cascade. The present study investigated the role of PKA in the expression of morphine and Δ9-THC antinociceptive tolerance. Male Swiss Webster mice were treated chronically with morphine or Δ9-THC and the warm-water …