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Updated: Sep 2, 2025

Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
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Wnt3a/YTHDF1 Regulated Oxaliplatin-Induced Neuropathic Pain Via TNF-α/IL-18 Expression in the Spinal Cord

Xiaohui Bai1, Yongtian Huang2, Wan Huang2

  • 1Department of Anesthesiology, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang Road West, Guangzhou, China.

Cellular and Molecular Neurobiology
|August 8, 2022
PubMed

Insights

Oxaliplatin chemotherapy can cause neuropathic pain (NP). This study reveals YTHDF1 upregulation promotes NP by activating Wnt3a signaling, leading to increased TNF-α and IL-18, offering new therapeutic targets for NP.

Area of Science:

  • Neuroscience
  • Oncology
  • Molecular Biology

Background:

  • Oxaliplatin is a crucial chemotherapy agent, but it frequently induces neuropathic pain (NP).
  • Understanding the molecular mechanisms behind oxaliplatin-induced NP is essential for developing effective pain management strategies.
  • YTHDF1, a key mediator in RNA modification, has emerged as a potential player in pathological processes.

Purpose of the Study:

  • To investigate the role of YTHDF1 in the development of oxaliplatin-induced neuropathic pain (NP).
  • To elucidate the molecular pathway involving YTHDF1 in this pain model.
  • To identify potential therapeutic targets for mitigating oxaliplatin-induced NP.

Main Methods:

  • Utilized immunohistochemistry and Western blotting to assess protein expression in mice.
  • Employed intrathecal siRNA injection and viral spinal microinjection in YTHDF1flox/flox mice for gene knockdown.
  • Assessed neuropathic pain behaviors using Von Frey, acetone, and ethyl chloride tests.

Main Results:

  • YTHDF1, Wnt3a, TNF-α, and IL-18 were significantly upregulated in mice treated with oxaliplatin.
  • Targeted inhibition of YTHDF1, Wnt3a, or downstream signaling pathways attenuated mechanical and cold allodynia.
  • Silencing YTHDF1 or inhibiting Wnt3a/Wnt signaling reduced TNF-α and IL-18 levels.

Conclusions:

  • YTHDF1 plays a critical role in mediating oxaliplatin-induced neuropathic pain.
  • A novel Wnt3a/YTHDF1-cytokine pathway contributes to NP pathogenesis.
  • YTHDF1 acts downstream of Wnt3a signaling to promote TNF-α and IL-18 translation, presenting a potential therapeutic target.
Keywords:
IL18Neuropathic painTNF alphaWntYTHDF1

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