This renewal of a Fogarty International Research Collaboration Award builds on collaboration between the P.I., Dr. Fie Luo, in Beijing China and Drs. Jingyu Chang and D. Woodward at the Neuroscience Research Institute of North Carolina. The goal was to coordinate a common effort to understand the time course of effect and mechanisms of action of deep brain stimulation on different brain structures for Parkinson's disease, epilepsy control, and related brain functions. Initial studies focused on restoration of function in models of Parkinson's disease in rodent. A major effort included sharing and establishing advanced instrumentation for combined stimulation and recording at Dr. Luo's laboratory that was developed at the USA site specifically for these studies. Success of our joint effort led to the appointment of Dr. Lou to Professor along with new laboratory resources at the Institute of Psychology Chinese Academy of Science. Our group is now positioned to expand substantially the research theme of DBS mechanism to include regulation of central pain pathways under neuropathic conditions. Continual development of new recording capabilities at the North Carolina site will expand the capacities at Beijing in parallel with other supported groups. The goal of the current study is to elucidate mechanisms underlying effective deep brain stimulation (DBS) under chronic pain conditions.
Aim 1 is to employ ensemble neuron recording in multiple regions to investigate the dynamic changes of ensemble neural activity in the thalamocortical pathways during the time course following the induction of pain by local inflammation or by ligation of spinal nerve. The goal is to test the hypothesis that peripheral inflammation or neuropathy will disrupt normal neuronal processing in these pathways.
Aim 2 is to study the neural responses of thalamocortical circuit to the behaviorally effective DBS in the rat models of chronic pain. The goal is to test the hypothesis that high frequency stimulation of VPL (ventral posterior lateral nucleus of thalamus) and PAG (periaqueductal gray) restored normal processing in the thalamocortical pathways that are not regulated correctly in the chronic pain condition. Multiple channel single-unit electrophysiological recording techniques in awake freely- moving animals will be employed to reveal the dynamic activity pattern of neurons in thalamocortical areas. Inflammatory pain induced by Freund's complete adjuvant, and spinal nerve ligation induced neuropathic pain models, will be used to mimic two major types of clinical chronic pain syndromes. This study will substantially advance our knowledge about the mechanisms underlying analgesic effect of DBS. Furthermore, success of this study will lay the groundwork for a future goal of using real-time neural network information obtained from recording ensemble thalamocortical neural activity to improve and optimize the effects of DBS in pain patients. Our collaboration will continue a basic investigation of multiple functions of the central brain regions related to pain regulation.

Public Health Relevance

Pain is a common neurological disorder affecting millions of patients. Many of these patients are not responsive to conventional medical treatment. Deep brain stimulation thus provides a promising alternative for alleviate chronic pain. This research project will study the neural mechanisms underlying pain process and the effect of deep brain stimulation on chronic pain in animal models. The study will help us to better apply deep brain stimulation in the clinic to treat intractable pain.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Small Research Grants (R03)
Project #
5R03TW008038-02
Application #
7771725
Study Section
International and Cooperative Projects - 1 Study Section (ICP1)
Program Officer
Michels, Kathleen M
Project Start
2009-03-01
Project End
2012-02-28
Budget Start
2010-03-01
Budget End
2011-02-28
Support Year
2
Fiscal Year
2010
Total Cost
$33,502
Indirect Cost
Name
Institute of Psychology
Department
Type
DUNS #
544962640
City
Beijing
State
Country
China
Zip Code
10010-1
He, Chun-Hong; Yu, Feng; Jiang, Zhao-Cai et al. (2014) Fearful thinking predicts hypervigilance towards pain-related stimuli in patients with chronic pain. Psych J 3:189-200
Jiang, Zhao-Cai; Pan, Qi; Zheng, Chun et al. (2014) Inactivation of the prelimbic rather than infralimbic cortex impairs acquisition and expression of formalin-induced conditioned place avoidance. Neurosci Lett 569:89-93
Wang, Ning; Shi, Miao; Wang, Jin-Yan et al. (2013) Brain-network mechanisms underlying the divergent effects of depression on spontaneous versus evoked pain in rats: a multiple single-unit study. Exp Neurol 250:165-75
Qi, Wei-Jing; Wang, Wei; Wang, Ning et al. (2013) Depressive-like history alters persistent pain behavior in rats: Opposite contribution of frontal cortex and amygdala implied. Psych J 2:133-145
Li, Sheng-Guang; Wang, Jin-Yan; Luo, Fei (2012) Adult-age inflammatory pain experience enhances long-term pain vigilance in rats. PLoS One 7:e36767
Su, Yuan-Lin; Huang, Jin; Wang, Ning et al. (2012) The effects of morphine on basal neuronal activities in the lateral and medial pain pathways. Neurosci Lett 525:173-8
Zhang, Yang; Wang, Ning; Wang, Jin-Yan et al. (2011) Ensemble encoding of nociceptive stimulus intensity in the rat medial and lateral pain systems. Mol Pain 7:64
Li, Xianghong; Luo, Fei; Shi, Lihong et al. (2011) Ensemble neural activity of the frontal cortical basal ganglia system predicts reaction time task performance in rats. Neurosci Res 71:149-60
Wang, Yan; Wang, Jin-Yan; Luo, Fei (2011) Why self-induced pain feels less painful than externally generated pain: distinct brain activation patterns in self- and externally generated pain. PLoS One 6:e23536
Li, Xiang-Hong; Wang, Jin-Yan; Gao, Ge et al. (2010) High-frequency stimulation of the subthalamic nucleus restores neural and behavioral functions during reaction time task in a rat model of Parkinson's disease. J Neurosci Res 88:1510-21

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