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The indirect pathway of the nucleus accumbens shell amplifies neuropathic pain

Nature Neuroscience volume 19, pages 220222 (2016) | Download Citation

Abstract

We examined adaptations in nucleus accumbens (NAc) neurons in mouse and rat peripheral nerve injury models of neuropathic pain. Injury selectively increased excitability of NAc shell indirect pathway spiny projection neurons (iSPNs) and altered their synaptic connectivity. Moreover, injury-induced tactile allodynia was reversed by inhibiting and exacerbated by exciting iSPNs, indicating that they not only participated in the central representation of pain, but gated activity in ascending nociceptive pathways.

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Acknowledgements

We thank the laboratory of S.M. Sternson (Howard Hughes Medical Institute) for providing technical help and chemical compound PSEM89S, and H. Fields for critically reading an earlier version of the manuscript. This work was supported by US National Institutes of Health grants DE022746 (A.V.A.), NS064091 (M.M.), NS 34696 and JPB Foundation (D.J.S.), and National Natural Science Foundation of China U1201223 (X.L.).

Author information

Author notes

    • A Vania Apkarian
    • , Marco Martina
    •  & D James Surmeier

    These authors contributed equally to this work.

Affiliations

  1. Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

    • Wenjie Ren
    • , Maria Virginia Centeno
    • , Sara Berger
    • , Jyothisri Kondapalli
    • , A Vania Apkarian
    • , Marco Martina
    •  & D James Surmeier
  2. Pain Research Center and Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.

    • Ying Wu
    • , Xiaodong Na
    •  & Xianguo Liu

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Contributions

W.R. performed the electrophysiological recordings, morphological reconstruction, data analysis and drafted the manuscript. M.V.C. performed surgeries, behavioral testing and analysis. S.B. performed behavioral testing and analysis. Y.W. and X.N. performed surgeries, western blot analysis and microdialysis. X.L. designed and supervised western blot and microdialysis experiments. J.K. generated the AAV virus for stereotaxic injections. D.J.S., A.V.A. and M.M. conceived of and designed the project, supervised the experiments and drafted the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to D James Surmeier.

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DOI

https://doi.org/10.1038/nn.4199

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