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Connections between EM2- and SP-containing terminals and GABAergic neurons in the mouse spinal dorsal horn

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Abstract

Endomorphin-2 (EM2) demonstrates a potent antinociceptive effect in pain modulation. To investigate the potential interactions of EM2- and substance P (SP)-containing primary afferents and γ-amino butyric acid (GABA)-containing interneurons in lamina II in nociceptive transmission, connections between EM2- and SP-containing terminals and GABAergic neurons in the spinal dorsal horn were studied. Double-immunofluorescent labeling showed that approximately 62.3 % of EM2-immunoreactive neurons exhibited SP-immunostaining, and 76.9 % of SP-immunoreactive neurons demonstrated EM2-immunoreactivities in the dorsal root ganglion (DRG). Dense double-labeled EM2- and SP-immunoreactivities were mainly observed in lamina II of the lumbar dorsal horn. Furthermore, triple-immunofluorescent labeling results revealed that EM2 and SP double-labeled terminals overlapped with GABAergic neurons. Immuno-electron microscopy confirmed that the EM2- or SP-immunoreactive terminals formed synapses with GABA-immunoreactive dendrites in lamina II of the lumbar dorsal horn. During noxious information transmission induced by formalin plantar injection, GABAergic neurons expressing FOS in their nuclei were contacted with EM2- or SP-immunoreactive terminals. These results suggest that the interactions between EM2- and SP-containing terminals and GABAergic interneurons in the lamina II influence pain transmission and modulation in the spinal dorsal horn.

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Acknowledgments

This work was supported by the grants from National Natural Science Foundation of China (Nos. 30971123, 31010103909, 31100861, 81200867, 81371239).

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Authors and Affiliations

  1. Department of Anatomy, Histology and Embryology, Basic Medical College, Fujian Medical University, Fuzhou, 350004, China

    Dao-Shu Luo, Wei Wang & Yun-Qing Li

  2. Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University, No. 169 West Changle Road, Xi’an, 710032, People’s Republic of China

    Jing Huang, Yu-Lin Dong, Zhen-Yu Wu, Yan-Yan Wei, Ya-Cheng Lu, Ya-Yun Wang, Sheng-Xi Wu & Yun-Qing Li

  3. Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi, 371-8511, Japan

    Yuchio Yanagawa

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  1. Dao-Shu Luo
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  2. Jing Huang
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  9. Sheng-Xi Wu
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  10. Wei Wang
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Corresponding authors

Correspondence to Wei Wang or Yun-Qing Li.

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D.-S. Luo and J. Huang contributed equally to this work.

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Luo, DS., Huang, J., Dong, YL. et al. Connections between EM2- and SP-containing terminals and GABAergic neurons in the mouse spinal dorsal horn. Neurol Sci 35, 1421–1427 (2014). https://doi.org/10.1007/s10072-014-1774-9

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  • DOI: https://doi.org/10.1007/s10072-014-1774-9

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