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Past Pilot Leaders


Dr. Guanglong He                                           

Assistant Professor, School of Pharmacy

ghe@uwyo.edu | (307) 766-6637 | Health Sciences Ctr 562

The Role of Innate Immune Response in Regulating Neuro-Inflammatory Pain

Project Summary:

Neuropathic pain poses a huge burden on public health and significantly affects quality of life. Yet the current therapies are often inadequate. Therefore, there is an urgent need for a better understanding of the underlying causes of this neuropathic condition. In this pilot project, I propose to study the role of innate immune response in the pathogenesis and progression of inflammatory pain with an eye on potential immunotherapies for pain management. The project addresses an important public health concern of neuro-inflammation and associated neuropathic pain. Using a unique mouse model of innate immune deficiency (CARD9 KO), I will test the hypothesis that innate immune response signaling regulates neuro-inflammation and associated neuropathic pain.

     It is postulated that cytokines/chemokines sustain neuro-inflammation and neuropathic pain by acting on sensory cells such as Schwann cells in DRG neurons resulting in peripheral sensitization. These cytokines/chemokines further induce inflammatory cell infiltration with continuous production of pro-inflammatory molecules such as IL-1β, IL-6, TNFα, CXCL-1, and MCP-1. The major inflammatory cell types involved are neutrophils and macrophages. CARD9 is a central regulator of the innate immune response and is associated with immune cell activation and inflammatory response. CARD9 signaling plays a pivotal role in the infiltration of macrophages/neutrophils and production of cytokines/chemokines in obesity and myocardial infarction, suggesting a detrimental effect in sterile inflammation. Therefore, inhibition of CARD9 signaling would attenuate inflammatory response to nerve injury or irritant-induced inflammatory pain. The proposed study is expected to fill a knowledge gap on the mechanistic link between the CARD9 innate immune response signaling and neuropathic and inflammatory pain.

     There are two specific aims: 1) to determine the regulatory role of CARD9 innate immune signaling on peripheral sensitization of inflammatory pain induced by chemical irritants; 2) to determine if a specific IL-1beta receptor antagonist could partially recapitulate the effect of CARD9 KO and suppress the peripheral sensitization. The outcome will help develop strategies to reduce chronic inflammatory pain with an overall impact on reducing public health burden and improving quality of life. The study may also have a broad impact on other chronic pains resulting from physical nerve damage, diabetes, and chemotherapy.

 


 

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Dr. Qian-Quan Sun, SBC Director, Professor

Department of Zoology and Physiology

Laramie, WY 82071

Phone: 307-766-5602

Email: neuron@uwyo.edu

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