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Peripheral BDNF Regulates Somatosensory–Sympathetic Coupling in Brachial Plexus Avulsion-Induced Neuropathic Pain

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Abstract

Brachial plexus avulsion (BPA) is a combined injury involving the central and peripheral nervous systems. Patients with BPA often experience severe neuropathic pain (NP) in the affected limb. NP is insensitive to the existing treatments, which makes it a challenge to researchers and clinicians. Accumulated evidence shows that a BPA-induced pain state is often accompanied by sympathetic nervous dysfunction, which suggests that the excitation state of the sympathetic nervous system is correlated with the existence of NP. However, the mechanism of how somatosensory neural crosstalk with the sympathetic nerve at the peripheral level remains unclear. In this study, through using a novel BPA C7 root avulsion mouse model, we found that the expression of BDNF and its receptor TrκB in the DRGs of the BPA mice increased, and the markers of sympathetic nervous system activity including α1 and α2 adrenergic receptors (α1-AR and α2-AR) also increased after BPA. The phenomenon of superexcitation of the sympathetic nervous system, including hypothermia and edema of the affected extremity, was also observed in BPA mice by using CatWalk gait analysis, an infrared thermometer, and an edema evaluation. Genetic knockdown of BDNF in DRGs not only reversed the mechanical allodynia but also alleviated the hypothermia and edema of the affected extremity in BPA mice. Further, intraperitoneal injection of adrenergic receptor inhibitors decreased neuronal excitability in patch clamp recording and reversed the mechanical allodynia of BPA mice. In another branch experiment, we also found the elevated expression of BDNF, TrκB, TH, α1-AR, and α2-AR in DRG tissues from BPA patients compared with normal human DRGs through western blot and immunohistochemistry. Our results revealed that peripheral BDNF is a key molecule in the regulation of somatosensory-sympathetic coupling in BPA-induced NP. This study also opens a novel analgesic target (BDNF) in the treatment of this pain with fewer complications, which has great potential for clinical transformation.

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The original contributions presented in the study are included in the article, and further inquiries can be directed to the corresponding authors.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (82072526, 82171212, and 81870867).

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Author notes

  1. Hang Xian, Huan Guo and Yuan-Ying Liu have contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopedics, Xijing Hospital, The Air Force Medical University, Xi’an, 710032, China

    Hang Xian, Jian-Lei Zhang, Rui Zhao, Hang Zhang & Rui Cong

  2. Pain and Related Diseases Research Laboratory, Medical College of Shantou University, Shantou, 515041, China

    Huan Guo

  3. School of Life Science and Research Center for Resource Peptide Drugs, Shaanxi Engineering and Technological Research Center for Conversation and Utilization of Regional Biological Resources, Yanan University, Yanan, 716000, China

    Yuan-Ying Liu

  4. Department of Neurobiology, School of Basic Medicine, The Air Force Medical University, Xi’an, 710032, China

    Huan Guo, Yuan-Ying Liu, Wen-Chao Hu & Rou-Gang Xie

  5. The Sixth Regiment, School of Basic Medicine, The Air Force Medical University, Xi’an, 710032, China

    Wen-Chao Hu

  6. The Tenth Squadron of the Third Regiment, School of Basic Medicine, The Air Force Medical University, Xi’an, 710032, China

    Ming-Jun Yu

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  1. Hang Xian
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Correspondence to Rou-Gang Xie, Hang Zhang or Rui Cong.

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Xian, H., Guo, H., Liu, YY. et al. Peripheral BDNF Regulates Somatosensory–Sympathetic Coupling in Brachial Plexus Avulsion-Induced Neuropathic Pain. Neurosci. Bull. 39, 1789–1806 (2023). https://doi.org/10.1007/s12264-023-01075-0

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