2. Academic Validation
  3. Transcranial direct current stimulation alleviates chronic pain in knee osteoarthritis by modulating microglial and astrocytic polarization and neuroinflammation

Transcranial direct current stimulation alleviates chronic pain in knee osteoarthritis by modulating microglial and astrocytic polarization and neuroinflammation

  • Life Sci. 2025 Sep 1:376:123753. doi: 10.1016/j.lfs.2025.123753.
Rujuan Liu 1,  Ting Zhu 2,  Xiao Chu 3,  Yifan Xu 4,  Lin Wang 4,  Qi Wan 5,  Tieshan Li 6
Affiliations

Affiliations

  • 1 Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao 266000, China; Institute of Neuroregeneration & Neurorehabilitation, Department of Pathophysiology, Qingdao University, Qingdao, China.
  • 2 Institute of Neuroregeneration & Neurorehabilitation, Department of Pathophysiology, Qingdao University, Qingdao, China.
  • 3 Department of Pharmacy of Qingdao Municipal Hospital, Qingdao, China.
  • 4 Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao 266000, China.
  • 5 Faculty of Life and Health Sciences, Shenzhen University of Advanced Technology, Shenzhen, China. Electronic address: wanqi@suat-sz.edu.cn.
  • 6 Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao 266000, China. Electronic address: tieshanli@qdu.edu.cn.
PMID: 40409582 DOI: 10.1016/j.lfs.2025.123753
Abstract

Aims: Knee osteoarthritis (KOA) chronic pain is linked to neuroinflammation mediated by reactive astrocytes in the primary somatosensory cortex (S1). Reactive astrocytes are classified into neurotoxic A1 and neuroprotective A2 phenotypes, with activated microglia promoting A1 astrocyte formation during chronic pain progression. This study aimed to investigate whether transcranial direct current stimulation (tDCS) can alleviate KOA chronic pain by modulating glial phenotype conversion and neuroinflammatory processes.

Main methods: Rats received an intra-articular injection of monosodium iodoacetate (MIA) in the left knee to model KOA pain. Additionally, rats received intraperitoneal injections of the NF-κB Inhibitor BAY 11-7082 and underwent tDCS. Pain thresholds were assessed using von Frey filaments and a hot plate. Changes in microglia, astrocytes, and inflammatory factor expression were analyzed with Western blotting, immunofluorescence, and reverse transcription-quantitative PCR.

Key findings: At 4 and 7 days after MIA injection, microglia exhibited a proinflammatory M1 phenotype, accompanied by increased expression of IL-1α, TNF-α, and C1q. From day 7 to 21 post-injection, astrocytes displayed a neurotoxic A1 phenotype. The NF-κB/NLRP3/IL-18 signaling pathway was significantly upregulated in KOA rats. Treatment with BAY 11-7082 or tDCS significantly alleviated mechanical allodynia and thermal hyperalgesia, shifting microglia from M1 to M2 and astrocytes from A1 to A2 polarization, while suppressing the NF-κB/NLRP3/IL-18 pathway and reducing neuroinflammation.

Significance: These findings suggest that tDCS may alleviate KOA chronic pain through modulation of glial activation states and suppression of central neuroinflammation, highlighting its potential as a non-invasive therapeutic approach.

Keywords

Astrocytes polarization; Central sensitization; Chronic pain; Knee osteoarthritis; Neuroinflammation; Transcranial direct current stimulation.

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