3: Cav-1 in the dorsal root ganglion modulates neuropathic pain via regulation of dopamine D1 receptor

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic neuropathic pain, , , , , , , , , , Neuroimmunology, Behavioral studies

Background and Aims: Neuropathic pain has become the most common type of chronic pain, but its pathophysiological mechanism remains unclear, and there are currently no effective treatment methods in clinical practice. Increasing evidence indicates that the plasticity changes of dorsal root ganglion (DRG) neurons are the core feature of neuropathic pain. In our previous study, we used bioinformatics methods to screen out key genes related to neuropathic pain in rat DRG, among which the expression of Caveolin-1 (Cav-1) showed significant differences. Cav-1 is an important structural protein of membrane lipid rafts and participates in various signal transduction processes, but its specific role in neuropathic pain is still unclear. This study aims to explore the expression changes of Cav-1 in neuropathic pain and its possible mechanisms, with a particular focus on its regulatory effect on the dopamine D1 receptor, in order to provide new targets for clinical intervention.

Methods: A neuropathic pain model was established by using spared nerve injury (SNI). The expression and localization of Cav-1 in DRG were detected by immunofluorescence and Western blot. The inhibitor daidzein was used to knockdown Cav-1 in DRG, and the changes of dopamine D1 receptor (D1R) induced by SNI were observed. Meanwhile, the Cav-1 was overexpressed in the DRG of normal rats by adenovirus vector (AAV), and the expression level of D1R was detected. The dopamine D1 receptor inhibitor SCH23390 was given to evaluate its effect on the upregulation of D1R. The pain behavior changes were evaluated by behavioral tests (such as mechanical pain threshold). All experiments had corresponding control groups, and the data were analyzed using statistical software.

Results: After SNI surgery, the expression of Cav-1 in DRG neurons was significantly upregulated, and it was mainly located in the membrane lipid raft region. Knockdown of Cav-1 could significantly reverse the increase of D1R in DRG caused by SNI. In normal rats, overexpression of Cav-1 led to a significant increase in D1R expression in DRG, and administration of SCH23390 could partially inhibit this increase. Behavioral studies showed that knockdown of Cav-1 could alleviate mechanical pain sensitivity in SNI rats, while overexpression of Cav-1 induced hyperalgesia in normal rats, and this effect could be weakened by SCH23390. This suggests that Cav-1 participates in the occurrence of neuropathic pain by regulating D1R.

Conclusions: Cav-1 is continuously upregulated in neuropathic pain and participates in the transmission of pain signals by regulating the expression of dopamine D1 receptors. Knockdown of Cav-1 can reverse the increase in D1R induced by SNI and alleviate pain, while overexpression of Cav-1 induces hyperalgesia by upregulating D1R. Therefore, Cav-1 may be a potential therapeutic target for neuropathic pain, and targeting the Cav-1/D1R pathway is expected to provide new strategies for clinical treatment. This study provides preliminary evidence for the discovery of new targets.

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Presenting Author: Chunyan Cui
Submitting Author: Chunyan Cui

Senior Author: Qing Liu, Ying Zhang

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Qing Liu - The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University,
• Ying Zhang - The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University