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The over-production of TNF-α via Toll-like receptor 4 in spinal dorsal horn contributes to the chronic postsurgical pain in rat

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Abstract

Purpose

Many patients suffer from chronic postsurgical pain (CPSP) following surgery, and the underlying mechanisms are poorly understood. In the present work, using the skin/muscle incision retraction (SMIR) model, the role of spinal TLR4/TNF-α pathway in the induction of CPSP was evaluated.

Methods

Mechanical allodynia induced by SMIR was established in adult male Sprague–Dawley rats. The von Frey test was performed to evaluate the role of TLR4/TNF-α pathway on the mechanical allodynia. Western-blot and immunohistochemistry methods were adopted to understand the molecular mechanisms.

Results

SMIR surgery decreased the ipsilateral 50 % paw withdrawal threshold, lasting for at least 20 days. Western-blot analysis and immunohistochemistry revealed that SMIR surgery significantly upregulated the expression of TLR4 (p < 0.01) in glial cells on the ipsilateral side of spinal cord and increased TLR4 occurred on day 5 and was maintained to the end of the experiment (day 20). Similarly, tumor necrosis factor-alpha (TNF-α) was significantly increased on days 5, 10, and 20 on the ipsilateral side of spinal dorsal horn following SMIR surgery. Intraperitoneal injection of an inhibitor of TNF-α synthesis thalidomide at 50 or 100 mg/kg dose (but not 10 mg/kg dose) significantly ameliorated the reduced paw withdrawal threshold induced by SMIR surgery. Importantly, intrathecal delivery of a specific TLR4 antagonist (LPS-RS) at dose of 25 μg significantly attenuated mechanical allodynia and prevented the upregulation of TNF-α induced by SMIR surgery.

Conclusions

These findings suggest that the upregulation of TNF-α via TLR4 contributes to the development of CPSP in spinal dorsal horn.

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Conflict of interest

Hao Tang received a research grant from Science and Technology Project in Guangdong (2010B031600046). The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of General Internal Medicine, The First Affiliated Hospital of Sun Yat-sen University, Sun Yet-Sen University, 58 Zhongshan Rd. 2, Guangzhou, 510080, China

    Hao Tang, Zhongfu Ma, Yanbing Liang & Zhenyu Li

  2. Department of Pain, The First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan South Road, Urumqi, Xinjiang, 830054, China

    Yang Sun & Mingmin Yang

Authors
  1. Yang Sun
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Correspondence to Zhenyu Li.

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Sun, Y., Yang, M., Tang, H. et al. The over-production of TNF-α via Toll-like receptor 4 in spinal dorsal horn contributes to the chronic postsurgical pain in rat. J Anesth 29, 734–740 (2015). https://doi.org/10.1007/s00540-015-2011-2

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  • DOI: https://doi.org/10.1007/s00540-015-2011-2

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