Raf1 interacts with OIP5 to participate in oxaliplatin-induced neuropathic pain

Wenli Yu1, Zhenli Zheng1, Wei Wei1

  • 1Department of Human Anatomy, School of Basic Medicine, Zhengzhou University, Zhengzhou 450001, China; Institute of Neuroscience, Zhengzhou University, Zhengzhou 450052, China.

Life Sciences
|July 6, 2021
PubMed
Abstract

Insights

Oxaliplatin chemotherapy can cause nerve pain. This study found that Opa interacting protein 5 (OIP5) and Raf1 protein interaction contributes to this pain, suggesting OIP5 as a potential drug target.

Area of Science:

  • Neuroscience
  • Oncology
  • Pharmacology

Background:

  • Oxaliplatin is a platinum-based chemotherapy agent effective against cancer but known to cause severe chronic neuropathy.
  • The precise molecular mechanisms behind oxaliplatin-induced neuropathic pain remain largely unknown.
  • Opa interacting protein 5 (OIP5), a cancer/testis antigen, and Raf1, a protein kinase, have been implicated in various cancers, with Raf1 known to promote OIP5 expression.

Purpose of the Study:

  • To investigate the potential role of Raf1 and OIP5 in the development of oxaliplatin-induced neuropathic pain.
  • To elucidate the molecular interaction between Raf1 and OIP5 in the context of chemotherapy-induced nerve damage.

Main Methods:

  • An animal model of oxaliplatin-induced neuropathic pain was established via intraperitoneal injection.
  • OIP5 and Raf1 expression was inhibited in the dorsal root ganglion (DRG) using intrathecal injection of small interfering RNA (siRNA).
  • Pain behaviors were assessed using Von Frey filaments and acetone tests, while protein expression was analyzed by Western blot.

Main Results:

  • Elevated levels of phosphorylated Raf1 (p-Raf1) and OIP5 were observed in the DRGs of rats with oxaliplatin-induced neuropathic pain.
  • Inhibition of OIP5 expression using siOIP5 significantly alleviated mechanical allodynia and cold hyperalgesia, and reduced Raf1 protein levels.
  • Inhibition of Raf1 expression using siRaf1 suppressed OIP5 expression and attenuated oxaliplatin-induced neuropathic pain.

Conclusions:

  • Raf1 and OIP5 interact to play a critical role in oxaliplatin-induced neuropathic pain.
  • The specific expression pattern of OIP5 in normal tissues suggests its potential as a targeted therapeutic agent for mitigating oxaliplatin-induced nerve pain.

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