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Bradley K. Taylor, PhD

  • Professor

    Education & Training

  • Postdoctoral fellowship, University of California, San Francisco, 1995
  • PhD, University of California, San Diego, 1991
  • BS, University of California, Davis, 1986
Awards
University Research Professor, University of Kentucky, 2017
“Top Science Advance in Pain Research, 2012-2013”, NIH IPRCC, 2014
Chairmanships, NIH Study Section IFCN C Jan/2013, Aug/2013, Oct/2014, 2013-14
Wethington Award for Excellence in Research: Department of Physiology, UK, 2009-2017
Independent Scientist Award K02, NIH: NIDA, 2007-2012
Service Recognition, Study Section Regular Member, Center for Scientific Research, NIH, 2006-2010
Principal Investigator, Louisiana Board of Regents Neuroscience Training Grant, 2006-2008
Faculty Research Award for Outstanding Achievement, Tulane University, 2004
Sponsor of NIH-funded predoctoral (3) and postdoctoral (2) F-series fellows, 2001-2015
First Independent Research Support & Transition Award, NIH, 1998-2004
National Research Service Award, F32 Postdoctoral, NIH: NIDA, 1993-1995
Representative Publications

Dr. Taylor's publications can be viewed through NCBI.

Research, Clinical, and/or Academic Interests

Dr. Taylor’s laboratory investigates the mechanisms through which inflammation or injury produces changes in the peripheral nerve, spinal cord, and brain, leading to a transition from acute pain to chronic pathological pain. They explore innovative ideas using state-of-the art techniques to better understand the molecular neurobiology of pain sensitization and opioid dependence. For example, key projects are studying the contribution of endogenous neuropeptide receptor signaling to the suppression of chronic pain to answer the question: “after a traumatic injury, how does the body prevent the development of chronic pain?” By better understanding the body’s solutions to prevent the transition from acute to chronic pain, Dr. Taylor’s laboratory hopes to contribute to the development and validation of new pharmacotherapeutic approaches. In the long term, these could replace addictive opioid medications and become available to treat patients with intractable pain who cannot tolerate opioids. The laboratory has successfully competed for more than $17 million in continuous external research grant funding from the National Institutes of Health since 1999. As of 2022, Dr. Taylor has published over 110 peer-reviewed research and review articles, over three-quarters of them as first or senior author, including a manuscript published in Science in 2013 on the discovery that constitutive activity of opioid receptors leads to long-term pain relief, which not only has proven to be significant in the scientific community, but also gained media attention in BusinessWeekNew Scientist, and the journal Nature. Trained in pharmacology, biochemistry, physiology, and animal behavior, Dr. Taylor has more than three decades of working experience with advanced in vivo monitoring of neurotransmitter release, functional neuroanatomy using fluorescence microscopy, cardiovascular telemetric recordings, Cre transgenics and conditional gene expression in vivo, patch-clamp electrophysiology and Ca2+ imaging in live central nervous system (CNS) slices, in vivo pharmacology, and behavioral and molecular models of chronic pain and opioid dependence. These technical capabilities, combined with his excitement for innovation in neurobiology, allow his laboratory to continuously advance the research frontier in translational medicine. They explore innovative ideas using state-of-the art techniques to better understand the molecular neurobiology of pain sensitization and opioid dependence, and thus contribute to new pharmacotherapeutic approaches to the development of analgesic drugs.

Research Grants

updated April 2023

Pharmacology and spinal microcircuitry of neuropeptide Y receptors. Chronic neuropathic pain affects 7-10% of the general population. Quality of life is severely impaired due to increased drug prescriptions, visits to health care providers, and comorbidities, including anxiety and depression. Thus, there is a critical and pressing need to develop safe, nonaddictive, and efficacious analgesic drugs for neuropathic pain. This requires a better understanding of its mechanisms, which generally include alterations in ion channels and G-protein-coupled receptor, imbalances between excitatory and inhibitory signaling, and plasticity in the CNS. We and many others are working to understand these mechanisms in animal models, identify novel therapeutic targets, and then translate this knowledge to the development of new analgesic drugs for clinical practice. To this end, we have spent over 25 years studying the neuropeptidergic inhibition of spinal pain transmission with the aim to develop analgesic drugs that will target the NPY Y1 receptor in the dorsal horn. The Taylor lab’s initial R01 work (2001-2007) indicated that intrathecal administration of NPY acts in a dose- and receptor-dependent manner to reduce behavioral signs of inflammatory pain and peripheral neuropathic pain, setting the stage to determine the therapeutic potential of NPY ligands for chronic pain. During the 2nd phase of funding (2018-2014), they discovered that an injury-induced enhancement of endogenous NPY-Y1 receptor GPCR signaling could be maintained long enough to confine chronic inflammatory and neuropathic pain within a state of remission (Solway et al., PNAS, 2011). These findings provided a new approach to prevent or alleviate chronic pain: by facilitating endogenous NPY receptor analgesia in the CNS and maintain latent sensitization in remission. The third funding period (2015-2020) found that injury induces a sustained spinal release of NPY, leading to the inhibition of pronociceptive Npy1r-expressing interneurons in the dorsal horn. During the fourth and current funding period (2021-2026), they are implementing transformative neuroscience and biomedical research approaches such as Cre-lox and FLP-FRT recombination technology to study how subpopulations of Npy1r-expressing neurons contribute to the microcircuitry of chronic pain modulation in the dorsal horn (Nelson et al., PNAS, 2022).

Chronic pain of type II diabetes. Painful diabetic neuropathy (PDN) is one of the common neurological complications in type 2 diabetes, presented by one-third of all community-based patients. In ZDF rats, Dr. Taylor’s group observed behavioral signs of motivational/affective pain (using a novel mechanical conflict-avoidance assay), and in both ZDF rats and db/db mice, they found elevated plasma methylglyoxal, a highly reactive byproduct of glucose metabolism that is markedly increased in the blood of hyperglycemic patients and contributes to PDN. To investigate MG-mediated mechanisms of pain, the Taylor laboratory established a mouse model of MG-induced pain (diabetic ZDF rat and db/db mouse) that includes multiple behavioral signs of spontaneous, evoked, and affective pain (using a conditioned place aversion assay), as well as molecular signs of spinal neuron activation. We reported that elevated MG causes PDN and that this metabolic hyperalgesia can be alleviated by drugs targeting MG, TRPA1, adenylyl cyclase 1, the small GTPase Epac, and the peroxisome proliferator-activated receptor γ, thus advancing a new pharmacotherapeutic strategy for painful diabetic neuropathy (Griggs et al., Neurobiology of Disease, 2019). This project is currently approaching the end of its third five-year NIH R01 cycle of funding (entire funding period: 2008-2024), and we are now thinking ahead to renew funding for this program in collaboration with Dr. Keiichiro Susuki at Wright State University to test the hypothesis that in spinal dorsal horn neurons, structural plasticity within the axon initial segment, a foundational element of neuronal sensitization, contributes to hypersensitivity in PDN.

MORCA analgesia and dependence. As initially reported in Science (Corder et al., Science 341: 1394-1399, 2013), the Taylor laboratory discovered that tissue inflammation, peripheral nerve injury, or surgical incision produces a latent sensitization (LS) of chronic pain that is tonically opposed by mu opioid receptor constitutive activity (MORCA) in the spinal cord and brain. They found that blockade of MORCA reinstated hyperalgesia, affective pain, and molecular and neurophysiological markers of spinal pain transmission – even when delivered more than a year after the induction and resolution of early acute pain. They also reported that LS can develop in humans, further implicating LS as an explanation for the episodic nature of chronic pain.

Recently, the basic science of their work has extended to the kappa opioid receptor and is now combining a variety of approaches, including fluorescent in situ hybridization, RNA sequencing, slice electrophysiology, fiber photometry, and GCaMP imaging, together with behavioral models of chronic pain, to determine whether MORCA in the spinal cord and brain (amygdala and rostral ventral medulla [RVM]) constrains chronic pain within a state of remission. They are thinking ahead to renew their R01 (2016-2022), with the goal to better understand how MORCA synergizes with other pain inhibitory GPCRs (including neuropeptide Y1 and kappa opioid receptors) on MOR- and KOR-expressing neurons in the spinal cord and RVM. With this work, their lab hopes to ultimately generate clinical trials to either: a) facilitate endogenous opioid receptor analgesia, thus restricting chronic pain within a state of remission; or b) extinguish chronic pain altogether.

Central neuropathic pain of multiple sclerosis (MS). MS is an autoimmune disease of the CNS associated with demyelination and inflammation as well as motor, sensory, and cognitive deficits. Neuropathic pain is a common comorbidity in MS affecting over half of people living with the disease. Current treatments for MS were designed to delay motor symptom progression, but have not limited MS-associated neuropathic pain, for which underlying mechanisms are poorly understood. The pathophysiology of MS includes microglial activation that is recapitulated in experimental autoimmune encephalomyelitis (EAE) mouse models of MS. The Taylor laboratory is using pharmacology and cre transgenics in EAE to test the hypothesis that central lesions associated with MS cause changes that signal the initiation and maintenance of neuropathic allodynia: 1) microglia in the dorsal horn of the spinal cord that can be targeted with drugs acting at the sphingosine-1-phosphate receptor 1; and 2) low threshold mechanoreceptors and thermosensors in primary afferent neurons.

Chronic pain and alcohol use disorder. Chronic pain is one of the hallmark symptoms of alcohol use disorder (AUD). Approximately half of AUD patients report an increase in pain sensitivity and severe pain during alcohol withdrawal. We have modeled chronic alcohol-withdrawal induced pain (CAWIP) as mechanical and heat hypersensitivity following exposure to four weeks of chronic intermittent delivery of ethanol vapor (CIEV). We recently established that: 1) CAWIP is dependent on number of alcohol exposure sessions; 2) the time course of mechanical and heat hypersensitivity is different; and 3) the intensity of hypersensitivity varies between the sexes (Brandner, Journal of Pain, 2023). To better understand the molecular and cellular underpinnings of CAWIP, we have teamed up with the laboratory of Dr. Sean Farris, also in the University of Pittsburgh Department of Anesthesiology and Perioperative Medicine. We are using transcriptional profiling of several brain regions with 3’-TagSeq, chemogenetics, as well as fiber photometry and behavioral pharmacology to test the central hypothesis that chronic alcohol exposure increases the activity of pronociceptive neurons and decreases pain inhibition, thus sensitizing the brain to CAWIP.