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Interleukin-1 Receptor Associated Kinase 1 Mediates the Maintenance of Neuropathic Pain after Chronic Constriction Injury in Rats

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Abstract

Neuropathic pain (NP) has complicated pathogenesis as it mainly involves a lesion or dysfunction of the somatosensory nervous system and its clinical treatment remains challenging. Chronic constriction injury (CCI) model is a widely used neuropathic pain model and involved in mechanisms including both nerve inflammatory and injury. Cytokines and their receptors play essential roles in the occurrence and persistence of neuropathic pain, but the underlying mechanisms have not well been understood. Therefore, Interleukin-1 receptor-associated kinase 1 (IRAK1) is chosen to explore the possible mechanisms of NP. In the present study, IRAK1 was found to persistently increase in the dorsal root ganglion (DRG) and spinal cord (SC) during CCI detected by western blot. The staining further confirmed that IRAK1 was mainly co-located in the DRG astrocytes or SC neurons, but less in the DRG microglia or SC astrocytes. Moreover, the region of increased IRAK1 expression was observed in superficial laminae of the spinal dorsal horn, which was the nociceptive neuronal expression domain, suggesting that IRAK1 may mediated CCI-induced pain by nociceptive primary afferent. In addition, intrathecal injection of Toll-like receptor 4 (TLR4) inhibitor or IRAK1 siRNA decreased the expression of IRAK1 accompanied with the alleviation of CCI-induced neuropathic pain. The upregulation of p-NF-κB expression was reversed by IRAK1 siRNA in SC, and intrathecal injection of p-NF-κB inhibitor relieved neuropathic pain. Taking together, targeting IRAK1 may be a potential treatment for chronic neuropathic pain.

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Acknowledgements

This work was supported in part by the National Science Foundation for Young Scientists of China (Nos. 81502053); Nantong science and technology project (MS22016008); Nantong science and technology project for Young Scientists (WQ2016085).

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  1. Dekun Yin and Yonglin Chen contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, 226001, China

    Yonglin Chen, Yao Li, Binbin Wang & Zhongling Xu

  2. Department of Anesthesiology, Funing People’s Hospital of Jiangsu, Yancheng, 224400, Jiangsu, China

    Dekun Yin

  3. Department of Anesthesiology, Taizhou People’s Hospital, Taizhou, 225300, Jiangsu, China

    Rongxiang Lu

  4. Laboratory Animal Center, Nantong University, Nantong, 226001, China

    Shunxing Zhu

  5. Department of Radiology, Zhongshan Hospital, Shanghai Institute of Medical Imaging, Department of Medical Imaging, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Bingbing Fan

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  1. Dekun Yin
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Correspondence to Bingbing Fan or Zhongling Xu.

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All procedures performed in studies involving animals were in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Animal Care and Use Committee of Nantong University.

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Yin, D., Chen, Y., Li, Y. et al. Interleukin-1 Receptor Associated Kinase 1 Mediates the Maintenance of Neuropathic Pain after Chronic Constriction Injury in Rats. Neurochem Res 44, 1214–1227 (2019). https://doi.org/10.1007/s11064-019-02767-8

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