A5034890502- Pain Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Neurotransmitter Receptor Influence on Behavior
- Sleep and Wakefulness Research
- Receptor Mechanisms and Signaling
- Circadian rhythm and melatonin
- Neuroscience and Neuropharmacology Research
- Stress Responses and Cortisol
- Pharmacological Receptor Mechanisms and Effects
- Tryptophan and brain disorders
- Ion channel regulation and function
- Neuroscience and Neural Engineering
- Botulinum Toxin and Related Neurological Disorders
- Musculoskeletal pain and rehabilitation
- Wnt/β-catenin signaling in development and cancer
- Anesthesia and Pain Management
- Dietary Effects on Health
- Liver physiology and pathology
- Autism Spectrum Disorder Research
- Drug Transport and Resistance Mechanisms
- Sleep and related disorders
- Cancer, Stress, Anesthesia, and Immune Response
- Urticaria and Related Conditions
- Synthesis of heterocyclic compounds
- Pain Management and Treatment
University of Massachusetts Chan Medical School
2009-2025
University of Pittsburgh
2017-2023
Boston University
2022-2023
University of Pittsburgh Medical Center
2017-2021
University of Pennsylvania
2020
The University of Texas MD Anderson Cancer Center
2013-2020
Allegheny Health Network
2020
Université Paris Cité
2012-2014
Délégation Paris 5
2012-2014
Centre National de la Recherche Scientifique
2014
Formalin injected subcutaneously into the paw is a frequently used pain assay; it evokes an initial period of licking and flinching followed by quiescence last second intense protracted flinching. The prominent phase believed to reflect development central (spinal cord) facilitation. This conclusion based on assumption that formalin burst activity in fine afferent fibers, prolonged low levels C fibers. Detailed reports substantiating this essential have not been published. Thus, we recorded...
Microglia are resident macrophages of the brain, performing roles related to brain homeostasis, including modulation synapses, trophic support, phagocytosis apoptotic cells and debris, as well protection repair. Studies assessing morphological transcriptional features microglia found regional differences sex in some investigated regions. However, markers used isolate many previous studies not expressed exclusively by or cannot be identify all contexts. Here, fluorescent activated cell...
Local protein synthesis in axons and dendrites underpins synaptic plasticity. However, the composition of machinery distal neuronal processes mechanisms for its activity-driven deployment to local translation sites remain unclear. Here, we employed cryo-electron tomography, volume electron microscopy, live-cell imaging identify Ribosome-Associated Vesicles (RAVs) as a dynamic platform moving ribosomes processes. Stimulation via chemically-induced long-term potentiation causes RAV...
While the molecular and cellular effects of opioids have been extensively studied, precise mechanisms by which these drugs target specific brain regions over time remain unclear. Similarly, despite well-documented sex differences in opioid responses, anatomical basis for this sexual dimorphism is not well characterized. To address questions, we developed an automated, scalable, unbiased approach whole-brain mapping neuronal activity marker c-Fos response to acute morphine exposure. Using...
Abstract Endogenous inflammatory mediators contribute to the pathogenesis of pain by acting on nociceptors, specialized sensory neurons that detect noxious stimuli. Here, we describe a new factor mediating pain. We show platelet-derived growth (PDGF)-BB applied in vitro causes repetitive firing dissociated nociceptor-like rat dorsal root ganglion and decreased their threshold for action potential generation. Injection PDGF-BB into paw produced nocifensive behavior rats led thermal mechanical...
Abstract Opioid craving and relapse vulnerability is associated with severe persistent sleep circadian rhythm disruptions. Understanding the neurobiological underpinnings of rhythms opioid use disorder (OUD) may prove valuable for developing new treatments addiction. Previous work indicated molecular disruptions in human brain OUD, highlighting synaptic alterations dorsolateral prefrontal cortex (DLPFC) nucleus accumbens (NAc)—key regions involved cognition reward, heavily implicated...
Mechanical sensitization is one of the most difficult clinical pain problems to treat. However, molecular and genetic bases mechanical nociception are unclear. Here we develop a <i>Drosophila</i> model investigate ion channels signaling pathways that regulate nociception. We fabricated von Frey filaments span subthreshold high noxious range for larvae. Using these, discovered pressure (force/area), rather than force per se, main determinant aversive rolling responses stimuli. demonstrated...
The safety and efficacy of opioids are compromised as analgesic tolerance develops. Opioids also ineffective against neuropathic pain. Recent reports have suggested that inhibitors the epidermal growth factor receptor (EGFR), a tyrosine kinase (RTK), may effects in cancer patients suffering from It has been shown platelet-derived receptor-β (PDGFR-β), an RTK to interact with EGFR, mediates opioid but does not induce analgesia. Therefore, we sought determine whether EGFR signaling was...
Neurons are highly differentiated and polarized cells, whose various functions depend upon the compartmentalization of ion channels. The rat hypothalamic-neurohypophysial system (HNS), in which cell bodies dendrites reside hypothalamus, physically separated from their nerve terminals neurohypophysis, provides a particularly powerful preparation to study distribution regional properties channel proteins. Using electrophysiological immunohistochemical techniques, we characterized...
Abstract Inhibitory control of excitatory networks contributes to cortical functions. Increasing evidence indicates that parvalbumin (PV+)-expressing basket cells (BCs) are a major player in maintaining the balance between excitation (E) and inhibition (I). Disruption E/I is believed be hallmark autism spectrum disorder (ASD). Here, we report lateralized decrease number PV+ BCs L2/3 somatosensory cortex dominant hemisphere Shank3−/− Cntnap2−/− mouse models ASD. The was identified during...
Cocaine dependence is a significant public health problem, characterized by periods of abstinence. Chronic exposure to drugs abuse induces important modifications on neuronal systems, including the dopaminergic system. The pattern administration an factor that should be taken into consideration study neuroadaptations. We compared effects intermittent (once daily) and binge (three times day) cocaine treatments for 1 (WD1) 14 (WD14) days after last injection spontaneous locomotor activity...
Abstract Opioids like fentanyl remain the mainstay treatment for chronic pain. Unfortunately, opioid's high dependence liability has led to current opioid crisis, in part, because of side‐effects that develop during long‐term use, including analgesic tolerance and physical dependence. Both opioids may lead escalation required doses achieve previous therapeutic efficacy. Additionally, altered sleep circadian rhythms are common people on therapy. impact rhythms, while disruptions likely...
Summary Striatal projection neurons (SPNs) are traditionally segregated into two subpopulations expressing dopamine (DA) D 1 -like or 2 receptors. However, this dichotomy is challenged by recent evidence. Functional and expression studies raise important questions: do SPNs co-express different DA receptors, these differences reflect unique striatal spatial distributions profiles? Using RNAscope in mouse striatum, we report heterogenous SPN distributed across dorsal-ventral rostral-caudal...
Background:Brain-derived neurotrophic factor (BDNF) is a neurotrophin that has long been studied in the field of addiction and its importance regulating drug addiction–related behavior widely demonstrated. The aim our study was to analyze consequences repeated exposure drugs abuse or natural reward on plasma BDNF levels during withdrawal.
Abstract Opioid craving and relapse vulnerability is associated with severe persistent sleep circadian rhythm disruptions. Understanding the neurobiological underpinnings of rhythms opioid use disorder (OUD) may prove valuable for developing new treatments addiction. Previous work indicated molecular disruptions in human brain OUD, highlighting synaptic alterations dorsolateral prefrontal cortex (DLPFC) nucleus accumbens (NAc)—key regions involved cognition reward, heavily implicated...
Opioids are some of the most potent analgesics available. However, their effectiveness is limited by development analgesic tolerance. Traditionally, tolerance was thought to occur termination <i>μ</i>-opioid receptor (MOR) signaling via desensitization and internalization. Contradictory findings led a more recent proposal that sustained MOR caused this view has also been called into question. We recently discovered platelet-derived growth factor receptor(PDGFR)-<i>β</i> system both necessary...
Abstract: Biosensors sensitive for in vivo monitoring of serotonin (5‐HT) the CNS by differential normal pulse voltammetry were constructed coating treated multi‐carbon fiber electrodes (mCFEs) with Nafion (N‐mCFE). In vitro sensitivities mCFE and N‐mCFE compared solutions ranging from 5 n M to 20 µ uric acid (UA), 5‐hydroxyindoleacetic (5‐HIAA), 5‐HT. The mCFEs three seven times less 5‐HIAA or UA than treatment dramatically decreased sensitivity N‐mCFEs (∼10 3 times), whereas it remained...