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Differential Changes in Neuronal Excitability in the Spinal Dorsal Horn After Spinal Nerve Ligation in Rats

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Abstract

Previous studies demonstrated that peripheral nerve injury induced excessive neuronal response and glial activation in the spinal cord dorsal horn, and such change has been proposed to reflect the development and maintenance of neuropathic pain states. The aim of this study was to examine neuronal excitability and glial activation in the spinal dorsal horn after peripheral nerve injury. We examined noxious heat stimulation-induced c-Fos protein-like immunoreactivity (Fos-LI) neuron profiles in fourth-to-sixth lumbar (L4–L6) level spinal dorsal horn neurons after fifth lumbar spinal nerve ligation (L5 SNL). Immunofluorescence labeling of OX-42 and GFAP was also performed in histological sections of the spinal cord. A significant increase in the number of Fos-LI neuron profiles in the spinal dorsal horn at the L4 level was found at 3 days after SNL, but returned to a level similar to that in sham-operated controls by 14 days after injury. As expected, a decrease in the number of Fos-LI neuron profiles in the spinal dorsal horn at the L5 level was found at 3 days after SNL. However, these profiles had reappeared in large numbers by 14 and 21 days after injury. Immunofluorescence labeling of OX-42 and GFAP indicated sequential activation of microglia and astrocytes in the spinal dorsal horn. We conclude that nerve injury causes differential changes in neuronal excitability in the spinal dorsal horn, which may coincide with glial activation. These changes may play a substantial role in the pathogenesis of neuropathic pain after peripheral nerve injury.

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Abbreviations

ANOVA:

Analysis of variance

DAB:

Diaminobenzidine

ERK:

Extracellular signal-regulated kinase

Fos-LI:

c-Fos protein-like immunoreactive

GFAP:

Glial fibrillary acidic protein

i.p.:

Intraperitoneal

PAP:

Peroxidase anti-peroxidase

PB:

Phosphate buffer

PBS:

Phosphate-buffered saline

p-ERK:

Phosphorylated ERK

SNL:

Spinal nerve ligation

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Acknowledgments

This study was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (16K11440).

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Authors and Affiliations

  1. Department of Oral Function and Anatomy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan

    Ryuji Terayama, Yuya Yamamoto, Noriko Kishimoto, Mitsuyasu Tabata, Kotaro Maruhama & Tomosada Sugimoto

  2. Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8525, Japan

    Yuya Yamamoto, Noriko Kishimoto, Mitsuyasu Tabata & Seiji Iida

  3. Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School, Okayama, 700-8525, Japan

    Ryuji Terayama, Kotaro Maruhama, Seiji Iida & Tomosada Sugimoto

Authors
  1. Ryuji Terayama
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  2. Yuya Yamamoto
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  3. Noriko Kishimoto
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Correspondence to Ryuji Terayama.

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Terayama, R., Yamamoto, Y., Kishimoto, N. et al. Differential Changes in Neuronal Excitability in the Spinal Dorsal Horn After Spinal Nerve Ligation in Rats. Neurochem Res 41, 2880–2889 (2016). https://doi.org/10.1007/s11064-016-2003-0

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  • DOI: https://doi.org/10.1007/s11064-016-2003-0

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