Chemotherapeutic drug elemene induces pain and anxiety-like behaviors by activating GABAergic neurons in the lateral septum of mice.

Abstract

Most chemotherapeutic drugs are potent and have a very narrow range of dose safety and efficacy, most of which can cause many side effects. Chemotherapy-induced peripheral neuropathy (CIPN) is the most common and serious side effect of chemotherapy for cancer treatment. However, its mechanism of action is yet to be fully elucidated. In the present study, we found that the treatment of the chemotherapy drug elemene induced hyperalgesia accompanied by anxiety-like emotions in mice based on several pain behavioral assays, such as mechanical allodynia and thermal hyperalgesia tests. Second, immunostaining for c-fos (a marker of activated neurons) further showed that elemene treatment activated several brain regions, including the lateral septum (LS), cingulate cortex (ACC), paraventricular nucleus of the thalamus (PVT), and dorsomedial hypothalamic nucleus (DMH), most notably in the GABAergic neurons of the lateral septum (LS). Finally, we found that both chemogenetic inhibition and apoptosis of LS neurons significantly reduced pain- and anxiety-like behaviors in mice treated with elemene. Taken together, these findings suggest that LS is involved in the regulation of elemene-induced chemotherapy pain and anxiety-like behaviors, providing a new target for the treatment of chemotherapy pain induced by elemene.

• Authors: Shanshan Sun, Jiayun Xu, Lin Lin, Mengxian Jia, Xiumin Xue, Qian Wang, Danni Chen, Zhihui Huang, Yongjie Wang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 699 Pg. 149548 (Mar 05 2024) ISSN: 1090-2104 [Electronic] United States
• PMID: 38281329 (Publication Type: Journal Article)
• Copyright: Copyright © 2024 Elsevier Inc. All rights reserved.

Chemical References

• elemene
• Sesquiterpenes

Topics

• Mice
• Animals
• Pain
• Peripheral Nervous System Diseases (chemically induced)
• GABAergic Neurons
• Hyperalgesia (chemically induced, drug therapy)
• Anxiety (chemically induced)
• Sesquiterpenes