139: Role of spinal P2Y6 receptor in cisplatin-induced periptheral neuropathic pain model in rats.

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic cancer related pain, , , , , , , Pharmacological interventions, ,

Background and Aims: In patients experiencing unendurable chemotherapy-induced peripheral neuropathy (CIPN), reduction the dose or discontinuation of therapeutic chemotherapy may complicate cancer treatment and prognosis. The aim of this study was to investigate the role of spinal P2Y6 receptor in CIPN models in rats.

Methods: CIPN model was established through intraperitoneal administration of cisplatin (2 mg/kg) for four consecutive days. Mechanical allodynia was assessed using von Frey filaments To evaluate the role of P2Y6 receptor, intrathecal administration of the P2Y6 receptor antagonist MRS2578 and the agonist UDP was performed, followed by behavioral evaluations. In addition, the preventive effect of intrathecal MRS2587 on the development of pain was evaluated in both models. Spinal cord dorsal horn (SCDH) and dorsal root ganglion (DRG) tissues were collected for immunofluorescence and Western blot analysis. ELISA was used to quantify the levels of IL-1β, IL-6, and TNF-α.

Results: Intrathecal administration of MRS2578 led to a dose-dependent reduction in mechanical allodynia and intrathecal administration of UDP significantly exacerbated mechanical allodynia. Additionally, MRS2578 treatment led to a significant reduction in pro-inflammatory cytokines such as IL-6 and IL-1β in the SCDH, as well as decreased expression of apoptotic and inflammatory markers, including Caspase-3, COX-2, and PKC. Immunofluorescence staining and Western blot analysis revealed reduced microglial activation, indicated by lower Iba-1 expression in the SCDH and DRG following MRS2578 treatment.

Conclusions: P2Y6 receptor antagonist significantly reduces mechanical allodynia, neuroinflammation, and microglial activation, while activation of P2Y6 receptors exacerbates pain and inflammatory responses in the CIPN model. These findings may provide a strong rationale for further exploration of P2Y6 antagonists as novel treatments for chemothrapy –induced neuropathic pain conditions.

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Presenting Author: Hyung Gon Lee
Submitting Author: HYUNG GON LEE

Senior Author: Jeong Il Choi

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Woong Mo Kim: MD. PhD - Department of Anesthesia and Pain medicine, Chonnam National University hospital, Gwangju, Repulbic of korea.
• Jeong Il Choi: MD. PhD - Department of Anesthesia and Pain medicine, Chonnam National University hospital, Gwangju, Repulbic of korea.
• Dong Ho Kang - Department of Anesthesia and Pain medicine, Chonnam National University hospital, Gwangju, Repulbic of korea.
• Myung Ha Yoon: MD. PhD - Department of Anesthesia and Pain medicine, Chonnam National University hospital, Gwangju, Repulbic of korea.