1. Academic Validation
  2. Sulforaphane alleviates hyperalgesia and enhances analgesic potency of morphine in rats with cancer-induced bone pain

Sulforaphane alleviates hyperalgesia and enhances analgesic potency of morphine in rats with cancer-induced bone pain

  • Eur J Pharmacol. 2021 Oct 15;909:174412. doi: 10.1016/j.ejphar.2021.174412.
Jie Fu 1 Miao Xu 1 Longsheng Xu 1 Huadong Ni 1 Baoxia Zhao 1 Chaobo Ni 1 Mingde Huang 1 Jianjun Zhu 1 Ge Luo 1 Ming Yao 2
Affiliations

Affiliations

  • 1 Department of Anesthesiology and Pain Research Center, Affiliated Hospital of Jiaxing University & The First Hospital of Jiaxing, Jiaxing, China.
  • 2 Department of Anesthesiology and Pain Research Center, Affiliated Hospital of Jiaxing University & The First Hospital of Jiaxing, Jiaxing, China. Electronic address: [email protected].
Abstract

Due to the efficacy and tolerability of the available drugs, the current treatment for cancer-induced bone pain (CIBP) is not considered ideal, and new drugs are required for better treatment results. This study investigated whether intrathecal injection of sulforaphane (SFN) can modulates the noxious behavior associated with CIBP and enhances the analgesic effects of morphine and the possible mechanisms related to these effects were investigated. Walker256 breast Cancer cells were injected into the bone marrow cavity of rats to establish the CIBP model. When CIBP rats began to exhibit painful behavior (CIBP 6 days), SFN was injected intrathecally for 7 days. The results showed that SFN alleviated the painful behavioral hypersensitivity caused by Cancer, accompanied by nuclear factor, erythroid 2 like 2 (Nrf2), Haem oxygenase 1 (HO-1) activation, nuclear factor kappa B (NF-κB) inhibition and inflammation-related factors (tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-β), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) reduction. In addition, SFN treatment inhibited the proliferation of Walker 256 cells in a dose-dependent manner, promoted mu-opioid receptor (MOR) expression in SH-SY5Y cells and enhanced the antihyperalgesic effects of morphine on CIBP rats by restoring the downregulation of MOR expression in the spinal cord. Interestingly, the antihyperalgesic effects of SFN were partially blocked by Opioid Receptor antagonists. This study showed that SFN combined with morphine might be a new way to treat CIBP.

Keywords

Cancer-induced bone pain; HO-1; MOR; Nrf2; Spinal cord; Sulforaphane.

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