1. Academic Validation
  2. TNF-α Enhanced Activity of Sympathetic Neurons in Superior Cervical Ganglion to Promote Chronic Sleep Deprivation-Related Hyperalgesia

TNF-α Enhanced Activity of Sympathetic Neurons in Superior Cervical Ganglion to Promote Chronic Sleep Deprivation-Related Hyperalgesia

  • Mol Neurobiol. 2025 Feb 24. doi: 10.1007/s12035-025-04790-z.
Fancan Wu # 1 Chao Fu # 2 Yalan Li 3 Hanbing Wang 4
Affiliations

Affiliations

  • 1 Department of Anesthesiology, The First People's Hospital of Foshan, Number 81, North of Ling Nan Road, Foshan, 528000, Guangdong, China.
  • 2 Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Number 613, The West of Huangpu Avenue, Tianhe Region, Guangzhou, 510630, Guangdong Province, China.
  • 3 Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Number 613, The West of Huangpu Avenue, Tianhe Region, Guangzhou, 510630, Guangdong Province, China. tyalan@jnu.edu.cn.
  • 4 Department of Anesthesiology, The First People's Hospital of Foshan, Number 81, North of Ling Nan Road, Foshan, 528000, Guangdong, China. fswhbing@126.com.
  • # Contributed equally.
Abstract

The mechanisms underlying the association between sleep deprivation (SD) and hyperalgesia remain incompletely understood. In this study, the Modified Horizontal Platform Method was employed to induce chronic SD. Neuropathic pain was induced using chronic constriction injury of the sciatic nerve. Pain-like behaviors were assessed through measurements of mechanical allodynia and thermal hyperalgesia, while gait analysis was used to evaluate motor function. Immunofluorescence and western blot analyses were conducted to examine the expression of TNF-α, Iba-1, TH, neurons and c-Fos. Apoptosis was assessed using TUNEL staining. To explore anatomical connections, anterograde and retrograde tracer viruses were injected into the superior cervical ganglion (SCG) and the spinal cord, respectively. Local injection of 6-OHDA was used to ablate sympathetic neurons in the SCG, and R-7050 was administrated to block the TNF-α receptor. We found that chronic SD induced hyperalgesia in both normal and neuropathic pain model, accompanied by significant infiltration of microglia in the dorsal horn. TH expression and apoptotic cells were increased in the SCG following chronic SD. Viral tracer results demonstrated the existence of anatomical connections between the SCG and the spinal cord. Ablation of sympathetic innervation improved pain-like behaviors and reduced microglia, without affecting movement. Furthermore, chronic SD led to increased expression of TNF-α in sympathetic neurons, which was associated with heightened SCG activity. Blocking the TNF-α receptor ameliorated pain-like behaviors, decreased microglia, reduced apoptosis, lowered SCG activity. In conclusion, TNF-α enhanced the activity of sympathetic neurons in the SCG, promoting hyperalgesia related to chronic SD.

Keywords

Chronic sleep deprivation; Hyperalgesia; SCG; Sympathetic neurons; TNF-α.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-110203
    99.96%, TNF Receptor Antagonist