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Updated: Oct 26, 2025

Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
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STING suppresses bone cancer pain via immune and neuronal modulation

Kaiyuan Wang1, Christopher R Donnelly2, Changyu Jiang3

  • 1Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA. kywang@tmu.edu.cn.

Nature Communications
|July 28, 2021
PubMed

Insights

Stimulator of interferon genes (STING) agonists effectively treat bone cancer pain and destruction. These immune regulators offer pain relief by modulating neurons, osteoclasts, and immune cells, improving patient outcomes.

Area of Science:

  • Immunology
  • Oncology
  • Neuroscience
  • Orthopedics

Background:

  • Bone metastasis causes severe pain and destruction in advanced cancers.
  • Current treatments for bone cancer pain are often ineffective.
  • The role of STING agonists in bone cancer pain management is unexplored.

Purpose of the Study:

  • To investigate the therapeutic potential of STING agonists in bone cancer.
  • To evaluate the effects of STING agonists on cancer pain, bone destruction, and tumor burden.
  • To elucidate the mechanisms underlying STING agonist-mediated effects.

Main Methods:

  • Utilized multiple mouse models of bone cancer.
  • Administered STING agonists systemically.
  • Assessed pain, locomotor function, bone destruction, and tumor burden.
  • Analyzed neuronal modulation, osteoclast function, and immune cell activity.
  • Investigated the dependence on host STING and IFN-I signaling.

Main Results:

  • STING agonists significantly reduced bone cancer pain and improved locomotor function.
  • STING agonists provided acute pain relief via direct neuronal modulation.
  • STING agonists protected against bone destruction and reduced tumor burden by modulating osteoclasts and immune cells.
  • Therapeutic effects were dependent on host STING and interferon-I signaling.

Conclusions:

  • STING activation is a promising strategy for managing bone cancer pain and associated pathologies.
  • STING agonists exert dual effects: acute pain relief through neuronal modulation and long-term benefits via immune and osteoclast modulation.
  • Targeting STING offers a novel therapeutic avenue for patients with advanced bone cancers.

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