I am a senior postdoctoral fellow with an abiding interest in chronic pain and motivated behavior. My immediate goal is to transition into a junior faculty position within the next two years, and I have assembled an in-depth training plan to achieve this goal. I have worked in the chronic pain field for the past 10 years and have ample experience with in vivo animal models of chronic pain and behavioral assays measuring evoked pain. I am proposing to pursue my K99 mentored phase at UC Los Angeles under the mentorship of Dr. Christopher Evans, exploring changes in dopamine (DA) transmission and motivated behavior in chronic pain. Dr. Evans is a highly respected scientist in the addiction fiel and has an outstanding track record in mentoring young researchers as they transition into independent faculty positions. Dr. Evans's lab is a member of the NIDA-funded Opioid Research Center, which houses unparalleled expertise and tools for investigating motivated behavior and opioid addiction. Through collaborations within this center, I will learn whole cell recording and assays in motivated behavior to better explore motivational deficits in chronic pain. These techniques will broaden my technical expertise and provide the necessary tools to achieve my research aims. In addition to the technical training I will receive during this mentored period, I have established a detailed training plan to develop complementary skills, including teaching and grant-writing, that will help me establish a successful independent research laboratory. My research investigates how chronic pain affects dopamine (DA) transmission and motivated behavior. In my previous postdoctoral fellowship, I found chronic pain resulted in a blunted opioid-stimulated DA response in the nucleus accumbens that interfered with mesolimbic-driven opioid reward. I hypothesize that changes in the mesolimbic DA system contribute to the motivational deficits in chronic pain, and strategies that recover DA signaling may prove effective targets in treating this condition. This application is a logical progression from these ideas, and is divided into two aims to be completed during the K99 and R00 phase, respectively.
The first aim will be to delineate the changes in VTA neuron excitability that underlies DA deficits in chronic pain. To achieve this, I will learn whole cell patch clamp recording and measure changes in inhibition on DAergic and GABAergic VTA neurons in an animal model of chronic pain. Moreover, I will explore how changes in VTA neuron excitability affect motivated behavior to rewards such as food and opioids.
The second aim of this proposal will be to determine the signals that are driving these pain-related changes in dopamine transmission and motivated behavior. I will use whole cell recording of VTA neurons to test for signaling molecules that contribute to these changes in VTA function in chronic pain. Because of the strong evidence for the corticotropin-releasing factor (CRF)/dynorphin system in mediating pain and DA signaling, I will start by exploring the effect of CRF in inhibiting DA signaling. Other signaling peptides, such as endogenous opioid peptides and other stress peptides will also be considered in the case that CRF proves unfruitful. Using the results from the electrophysiology experiments to inform the subsequent experiments, I will test the ability of interfering with peptide signaling on recovering opioid stimulated DA release and motivated behavior in chronic pain. These studies will expand our understanding of the affective changes in chronic pain and identify novel therapeutic interventions for the improved treatment of this disease.
Chronic pain is associated with an important affective component that has been largely unexplored in the basic science field. The goal of this study is to examine how chronic pain affects dopamine function and determine how these changes affect motivated behavior. The results from this project will expand our understanding of how motivational system changes in chronic pain and identify novel therapeutic targets to better treat this condition.
| Taylor, Anna M W (2018) Corticolimbic circuitry in the modulation of chronic pain and substance abuse. Prog Neuropsychopharmacol Biol Psychiatry 87:263-268 |
| Lee, Kevin; Vuong, Helen E; Nusbaum, David J et al. (2018) The gut microbiota mediates reward and sensory responses associated with regimen-selective morphine dependence. Neuropsychopharmacology 43:2606-2614 |
| Taylor, Anna M W; Mehrabani, Sadaf; Liu, Steve et al. (2017) Topography of microglial activation in sensory- and affect-related brain regions in chronic pain. J Neurosci Res 95:1330-1335 |
| Cahill, Catherine M; Taylor, Anna Mw (2017) Neuroinflammation-a co-occurring phenomenon linking chronic pain and opioid dependence. Curr Opin Behav Sci 13:171-177 |
| Cahill, Catherine M; Walwyn, Wendy; Taylor, Anna M W et al. (2016) Allostatic Mechanisms of Opioid Tolerance Beyond Desensitization and Downregulation. Trends Pharmacol Sci 37:963-976 |
