Peripheral inflammation and central sensitization associated with postoperative pain following arthroscopy surgery in rotator cuff injury

Radiol Med. 2026 Jan;131(1):147-157. doi: 10.1007/s11547-025-02079-8. Epub 2025 Oct 4.

Abstract

Purpose: Rotator cuff injury (RCI) is a prevalent cause of shoulder disability, with emerging evidence implicating localized inflammatory cascades as key mediators of nociceptive signaling. Recent studies suggest that preoperative central sensitization induced by exposure to inflammation serves as a predictor of persistent pain following surgery at one-year follow-up. However, the underlying mechanism between peripheral inflammation, central pain processing, and postsurgical pain remains poorly characterized in RCI. Therefore, we aim to characterize pain-elicited brain responses and identify brain mediators of pain hypersensitivity in RCI patients.

Materials and methods: Utilizing a case-control design, twenty-eight patients with right/bilateral RCI and twenty healthy controls underwent functional MRI during pressure noxious stimuli, with pain intensity quantified via the visual analog scale. Comprehensive analyses of preoperative resting-state fMRI, serum cytokine profiles, and postoperative neuroimaging were conducted in RCI patients.

Results: We found significantly higher level of pain sensitivity and IL-6 concentrations in RCI patients compared to controls. RCI patients exhibited higher activation within the left primary somatosensory cortex (S1), which mediated the relationship between IL-6 levels and pain sensitivity. Notably, preoperative S1 amplitude of low-frequency fluctuations (ALFF) exhibited a strong positive correlation with IL-6 concentrations (r = 0.62) and served as a robust predictor of postoperative pain reduction. These findings establish left S1 hyperactivation as a neuroplastic hub integrating peripheral inflammatory signaling (IL-6 elevation) and central pain sensitization in RCI.

Conclusion: The observed preoperative associations between S1 function, cytokine profiles, and postoperative pain resolution provide translational evidence for S1 as a predictive biomarker of pain chronification risk.

Keywords: Functional MRI; General liner model; Inflammation; Pain sensitization; Rotator cuff injury.

MeSH terms

  • Adult
  • Arthroscopy* / adverse effects
  • Case-Control Studies
  • Central Nervous System Sensitization* / physiology
  • Female
  • Humans
  • Inflammation* / physiopathology
  • Interleukin-6 / blood
  • Magnetic Resonance Imaging* / methods
  • Male
  • Middle Aged
  • Pain Measurement
  • Postoperative Pain* / diagnostic imaging
  • Postoperative Pain* / etiology
  • Postoperative Pain* / physiopathology
  • Rotator Cuff Injuries* / diagnostic imaging
  • Rotator Cuff Injuries* / surgery

Substances

  • Interleukin-6