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J Anesth. 2015 Oct;29(5):734-40. doi: 10.1007/s00540-015-2011-2. Epub 2015 Apr 18.

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

Author information

1
Department of Pain, The First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan South Road, Urumqi, Xinjiang, 830054, China.
2
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.
3
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. leezhenyu99@163.com.

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.

KEYWORDS:

Chronic postsurgical pain; SMIR; TLR4; TNF-α

PMID:
25895164
DOI:
10.1007/s00540-015-2011-2
[Indexed for MEDLINE]

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