¹National Cheng Kung University, Depart of Psychology, Tainan, Taiwan, ²National Cheng Kung University, Department of Pharmacology, Tainan, Taiwan

Background: Hyperalgesia, a pathological condition characterized by increased pain sensitivity, is a well-recognized consequence of chronic stress. Rodent studies have demonstrated that prolonged stress exposure lowers pain thresholds, resulting in the development of hyperalgesia. Previous research has indicated that exercise mitigates neuropathic pain through hypoalgesia, mediated by the activation of the ventral tegmental area (VTA) within the mesolimbic dopamine (DA) reward system. However, the potential of VTA activation as a therapeutic strategy for alleviating chronic stress-induced hyperalgesia remains to be elucidated.

Aims & Objectives: Our study is focused on determining whether activation of VTA could serve as a therapeutic strategy to mitigate chronic stress-induced hyperalgesia. The specific aims of the research are as follows:
1. To evaluate the effects of chronic restraint stress (CRS) on pain sensitivity.
2. To investigate the therapeutic potential of VTA activation.

Method: The Von Frey stimulation test was employed to assess pain thresholds in mice following 14 days of CRS. Additionally, excitatory DREADD (AAV9-hSyn-hM3D(Gq)-mCherry) was utilized to activate the VTA to investigate whether VTA activation influences pain sensitivity in mice subjected to 14 days of CRS as evaluated by the Von Frey stimulation test.

Results: Our study demonstrates that CRS-treated mice developed mechanical hyperalgesia, as evidenced by a significant reduction in their paw withdrawal threshold (PWT). Importantly, chemogenetic activation of the VTA successfully reversed this decreased PWT in CRS-treated mice.

Discussion & Conclusions: These findings shed light on the potential of VTA activation to alleviate hyperalgesia and offer insights into the underlying neural circuits, paving the way for novel therapeutic strategies for chronic stress-induced dysfunctions.