Syringaresinol Alleviates Oxaliplatin-Induced Neuropathic Pain Symptoms by Inhibiting the Inflammatory Responses of Spinal Microglia

Ji Hwan Lee, Jong Hee Choi, Jaihwan Kim, Tai Wan Kim, Ji Young Kim, Geehoon Chung, Ik Hyun Cho, Dae Sik Jang, Sun Kwang Kim

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Oxaliplatin-induced peripheral neuropathy (OIPN) is a serious side effect that impairs the quality of life of patients treated with the chemotherapeutic agent, oxaliplatin. The underlying pathophysiology of OIPN remains unclear, and there are no effective therapeutics. This study aimed to investigate the causal relationship between spinal microglial activation and OIPN and explore the analgesic effects of syringaresinol, a phytochemical from the bark of Cinnamomum cassia, on OIPN symptoms. The causality between microglial activation and OIPN was investigated by assessing cold and mechanical allodynia in mice after intrathecal injection of the serum supernatant from a BV-2 microglial cell line treated with oxaliplatin. The microglial inflammatory response was measured based on inducible nitric oxide synthase (iNOS), phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated nuclear factor-kappa B (p-NF-κB) expression in the spinal dorsal horn. The effects of syringaresinol were tested using behavioral and immunohistochemical assays. We found that oxaliplatin treatment activated the microglia to increase inflammatory responses, leading to the induction of pain. Syringaresinol treatment significantly ameliorated oxaliplatin-induced pain and suppressed microglial expression of inflammatory signaling molecules. Thus, we concluded that the analgesic effects of syringaresinol on OIPN were achieved via the modulation of spinal microglial inflammatory responses.

Original languageEnglish
Article number8138
JournalMolecules
Volume27
Issue number23
DOIs
Publication statusPublished - Dec 2022

Bibliographical note

Publisher Copyright:
© 2022 by the authors.

Keywords

  • inflammation
  • microglia
  • neuropathic pain
  • oxaliplatin
  • phytochemical
  • syrinagresinol

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