Pain is a multidimensional experience that includes sensory and affective components. Human imaging studies have identified patterns of activities within key cortical areas that can encode different pain experiences, but it remains unclear how pain can also be encoded reliably at the level of individual neurons or populations of neurons. The primary somatosensory cortex (S1) has been thought to be important in the sensory-discriminative aspect of the pain, yet the anterior cingulate cortex (ACC) is known to play a crucial role in the affective-motivational experience of pain. However, imaging studies cannot provide causal relationship between circuits and behavior and are further limited by poor temporal resolution. Therefore, a complete understanding of neural codes for acute pain in physiology remains missing. Neuromodulation is a potential option for pain treatment; but current techniques such as deep brain stimulation (DBS) lack optimal targets and require constant stimulation with undesired side effects. We will use a rat model to uncover pain mechanisms of key central neural circuits and develop a demand-based brain-machine interface (BMI) that integrates timely detection of the pain signal and precise temporal analgesic control.
In Aim 1, we will identify cortical circuitry for encoding acute pain. We will collect simultaneous S1 and ACC ensemble recordings from freely behaving rats and characterize their firing patterns at both single cell and population levels.
In Aim 2, we will determine how the central pain circuitry is altered by central vs. peripheral analgesic strategy using optogenetic and pharmacological approaches.
In Aim 3, we will develop reliable computational strategies to decode acute pain based on neural ensemble recordings from the central pain circuits involving S1 and ACC.
In Aim 4, we will develop a real-time closed-loop BMI system for modulating acute pain by combining a detection arm of neural decoding with a therapeutic arm of central neurostimulation. We will test its effectiveness using established pain behavior assays. Together, these results will enable us to dissect neural circuits and mechanisms for acute pain and provide a template for next-generation demand-based pain treatment.

Public Health Relevance

(See Instructions): This project is aimed to dissect circuit mechanisms of acute pain and develop closed-loop BMI system for pain control. We will combine experimental, computational and engineering techniques to decode acute pain signals and apply them to develop real-time BMI system for pain modulation using neurostimulation. The proposed research will not only reveal important mechanisms of acute pain, but will also provide new insiahts on theraoeutic treatment of oain analaesia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS100065-02
Application #
9313960
Study Section
Special Emphasis Panel (ZRG1-IFCN-B (50)R)
Program Officer
Oshinsky, Michael L
Project Start
2016-07-15
Project End
2020-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
2
Fiscal Year
2017
Total Cost
$370,781
Indirect Cost
$152,031
Name
New York University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Martinez, Erik; Lin, Harvey H; Zhou, Haocheng et al. (2017) Corticostriatal Regulation of Acute Pain. Front Cell Neurosci 11:146
Chen, Zhe; Zhang, Qiaosheng; Tong, Ai Phuong Sieu et al. (2017) Deciphering neuronal population codes for acute thermal pain. J Neural Eng 14:036023
Sun, Yongjun; Liu, Kevin; Martinez, Erik et al. (2017) AMPAkines and morphine provide complementary analgesia. Behav Brain Res 334:1-5
Chen, Zhe; Wilson, Matthew A (2017) Deciphering Neural Codes of Memory during Sleep. Trends Neurosci 40:260-275
Zhang, Qiaosheng; Manders, Toby; Tong, Ai Phuong et al. (2017) Chronic pain induces generalized enhancement of aversion. Elife 6:
Urien, Louise; Zhang, Qiaosheng; Martinez, Erik et al. (2017) Assessment of Aversion of Acute Pain Stimulus through Conditioned Place Aversion. Bio Protoc 7:
Su, Chen; Lin, Hau Yeuh; Yang, Runtao et al. (2016) AMPAkines Target the Nucleus Accumbens to Relieve Postoperative Pain. Anesthesiology 125:1030-1043