UC San Diego

Chronic pain is a major problem restraining people from performing everyday tasks. Recent studies showed that cholesterol metabolism in microglia regulates neuropathic pain, however, little is known about the unique role astrocytes play during chronic pain. In this thesis paper, we focused on exploring two main cholesterol transporters in astrocytes, ABCA1 and ABCG1, and their roles in controlling neuropathic pain. Here, we used the chemotherapy-induced peripheral neuropathy (CIPN) model in male mice with conditional deletion of ABCA1 and ABCG1 cholesterol transporters in astrocytes (ABC-iaKO) and male mice with constitutive deletion of apolipoprotein E (ApoE-KO) to examine their pain behavior response and analyze their glial and neuronal lipid composition using flow cytometry. We found that ABC-iaKO mice were not affected by the CIPN model and showed higher mechanical paw-withdrawal thresholds than wild-type mice. When looking into the lipid content of neurons, both ABC-iaKO and ApoE-KO mice subjected to chemotherapy treatment displayed a trend toward lower lipid droplets and lipid rafts levels compared to wild-type mice. Our findings demonstrate that ABCA1 and ABCG1 transporters in astrocytes play essential roles in regulating neuropathic pain response and possibly altering neuronal lipid content through ApoE. Through this study, we could further understand how astrocytic cholesterol regulates neuropathic pain and contribute to creating a safe treatment for chronic pain.