A5070480193- Neurotransmitter Receptor Influence on Behavior
- Pain Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Pharmacological Receptor Mechanisms and Effects
- Anesthesia and Pain Management
- Stress Responses and Cortisol
- Veterinary Pharmacology and Anesthesia
- Carbohydrate Chemistry and Synthesis
- Glycosylation and Glycoproteins Research
- Neuroendocrine regulation and behavior
- Memory and Neural Mechanisms
- Chemical Synthesis and Analysis
- Botulinum Toxin and Related Neurological Disorders
- Ion channel regulation and function
- Musculoskeletal pain and rehabilitation
- Forensic Toxicology and Drug Analysis
- Pain Management and Opioid Use
- Cancer, Stress, Anesthesia, and Immune Response
- Tryptophan and brain disorders
- Microtubule and mitosis dynamics
- Transcranial Magnetic Stimulation Studies
- Opioid Use Disorder Treatment
- Psychedelics and Drug Studies
Wake Forest University
2016-2025
Baylor College of Medicine
2018-2022
Winston-Salem/Forsyth County Schools
2011
Foundation for the National Institutes of Health
2006
Marymount University
2004
South London and Maudsley NHS Foundation Trust
2001
University of Konstanz
1992-1998
Atrium Health Wake Forest Baptist
1995-1997
Virginia Commonwealth University Medical Center
1989
Washington University in St. Louis
1985
Agonists targeting the kappa opioid receptor (KOR) have been promising therapeutic candidates because of their efficacy for treating intractable itch and relieving pain. Unlike typical narcotics, KOR agonists do not produce euphoria or lead to respiratory suppression overdose. However, they dysphoria sedation, side effects that precluded clinical development as therapeutics. signaling can be fine-tuned preferentially activate certain pathways over others, such bias so signals through G...
Cellular heterogeneity within the mammalian brain poses a challenge toward understanding its complex functions. Within olfactory bulb, odor information is processed by subtypes of inhibitory interneurons whose and functionality are influenced ongoing adult neurogenesis. To investigate this cellular better understand adult-born neuron development, we utilized single-cell RNA sequencing computational modeling to reveal diverse transcriptionally distinct neuronal nonneuronal cell types. We also...
Cardiac fibroblasts (CFs) respond to injury by transitioning through multiple cell states, including resting CFs, activated and myofibroblasts. We report here that Hippo signaling cell-autonomously regulates CF fate transitions proliferation, non-cell-autonomously both myeloid activation in the heart. Conditional deletion of pathway kinases, Lats1 Lats2 , uninjured CFs initiated a self-perpetuating fibrotic response adult heart was exacerbated myocardial infarction (MI). Single...
In previous studies from our laboratory, chronic noncontingent morphine administration decreased μ opioid receptor-activated G-proteins in specific brainstem nuclei. the present study, receptor binding and were examined after heroin self-administration. Rats trained to self-administer intravenous for up 39 d, achieving intake 366 mg · kg −1 d . opioid-stimulated [ 35 S]GTPγS 3 H]naloxone autoradiography performed adjacent brain sections. Agonist-stimulated also other G-protein-coupled...
Treatment of postsurgical pain is a major use analgesics, particularly after abdominal surgery. Analgesics display number limiting side effects, including sedation, cognitive impairment, and ileus. Although several postoperative rodent models have been developed, these do not address concerns.A model presented in the rat which subcostal incision performed, penetrating into peritoneal cavity. The behavioral effects this surgical procedure are assessed using exploratory locomotor activity...
Background Neuropathic pain is associated with several sensory abnormalities, including allodynia as well spontaneous pain. Opioid intake in neuropathic patients motivated by alleviation of both and allodynia. However, laboratory animal studies rely almost exclusively on reflexive withdrawal measures The authors examined the pharmacology self-regulated opioids rats or without nerve injury compared rate drug to reversal Methods Rats were implanted intravenous catheters, L5 L6 spinal nerves...
Chronic pain represents a mixture of pathophysiologic mechanisms, complex assortment spontaneous and elicited states, somewhat unpredictable response to analgesics. Opioids remain the mainstay treatment moderate severe chronic pain, although there is little systematic examination guide drug selection. Cyclooxygenase inhibitors play primarily an adjunctive role in treatment. Agents with activity acute such as antidepressants, antiepileptics, i.v. administered local anesthetics, are initiated...
Dopaminergic innervations of the nucleus accumbens (NAcc) have a significant role in brain processes underlying reinforcing actions abused drugs. In addition to evidence from selective lesions and receptor antagonists, recent determinations increased extracellular dopamine concentrations ([DA]e) this structure during cocaine ethanol self-administration extended notion. This study was undertaken determine if effects heroin were similarly correlated with changes [DA]e NAcc using vivo...
Fast-conducting myelinated high-threshold mechanoreceptors (AHTMR) are largely thought to transmit acute nociception from the periphery. However, their roles in normal withdrawal and nerve injury-induced hyperalgesia less well accepted. Modulation of this subpopulation peripheral neurons would help define behaviors. The optically active proton pump, ArchT, was placed an adeno-associated virus-type 8 viral vector with CAG promoter administered by intrathecal injection resulting expression...
Traditional analgesic opioid compounds, which act through μ receptors (MORs), engender a high risk for misuse and dependence. κ receptor (KOR) activation, potential target pain treatment, produces antinociception without euphoric side effects but results in dysphoria aversion. Triazole 1.1 is KOR agonist biased toward G-protein coupled signaling, potentially promoting dysphoria. We tested whether triazole could provide its combination with morphine. employed lactic acid abdominal model,...
Chronic postsurgical pain, a significant public health problem, occurs in 10 to 50% of patients undergoing major surgery. Acute pain induces endogenous analgesia termed conditioned modulation (CPM), and the strength CPM preoperatively predicts likelihood chronic pain. The relation between recovery from surgery has not been examined preclinical models.CPM was assessed individual rats correlated with each animal's time course hypersensitivity after partial spinal nerve ligation. role...
Opioids are powerful analgesics, but also common drugs of abuse. Few studies have examined how neuropathic pain alters the pharmacology opioids in modulating limbic pathways that underlie abuse liability.Rats with or without spinal nerve ligation (SNL) were implanted electrodes into left ventral tegmental area and trained to lever press for electrical stimulation. The effects morphine, heroin, cocaine on facilitating stimulation mechanical allodynia assessed SNL control subjects.Responding...
Although G protein-coupled receptor (GPCR) kinases (GRKs) have been shown to mediate desensitization of numerous GPCRs in studies using cellular expression systems, their function under physiological conditions is less well understood. In the current study, we employed various strategies assess effect inhibiting endogenous GRK2/3 on signaling and endogenously expressed s-coupled receptors human airway smooth muscle (ASM) cells. inhibition by a Gbetagamma sequestrant, dominant-negative...
Prescription opioid abuse is a significant concern in treating chronic pain, yet few studies examine how neuropathic pain alters the liability of commonly abused prescription opioids.Normal and spinal nerve ligated (SNL) rats were implanted with electrodes into left ventral tegmental area (VTA). Rats trained to lever press for intracranial electrical stimulation (VTA ICSS), effects methadone, fentanyl, hydromorphone, oxycodone on facilitation VTA ICSS assessed. A second group intrathecal...