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Convergent Nociceptive Input to Spinal Dorsal Horn Neurons After Peripheral Nerve Injury

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Abstract

The number of c-Fos protein-like immunoreactive (c-Fos-IR) neurons in the spinal dorsal horn evoked by noxious stimulation was previously shown to be increased following peripheral nerve injury, and this increase was proposed to reflect the neuropathic pain state. The aim of this study was to investigate whether anomalous convergent primary afferent input to spinal dorsal horn neurons contributed to nerve injury-induced c-Fos hyperinducibility. Double immunofluorescence labeling for c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) was performed to detect convergent synaptic input from different branches of the sciatic nerve after injury to the tibial nerve. c-Fos expression and the phosphorylation of ERK were induced by noxious heat stimulation of the hindpaw and also by electrical stimulation (ES) of the injured tibial nerve, respectively. The number of c-Fos-IR neurons was significantly decreased 3 days after the injury. However, the number of c-Fos-IR neurons returned to the control level 14 days after the injury. P-ERK immunoreactive (p-ERK-IR) neurons were induced in the central terminal field of the tibial nerve by ES of the tibial nerve. The topographic distribution pattern and number of such p-ERK-IR neurons remained unchanged after the nerve injury. The time course of changes in the number of double-labeled neurons, that presumably received convergent primary afferent input, showed a pattern similar to that of c-Fos-IR neurons after the injury. These results indicate that convergent primary nociceptive input through neighboring intact nerves may contribute to c-Fos hyperinducibility in the spinal dorsal horn.

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Abbreviations

ANOVA:

Analysis of variance

CNS:

Central nervous system

ES:

Electrical stimulation

c-Fos-IR:

c-Fos protein-like immunoreactive

MAPK:

Mitogen-activated protein kinase

p-ERK:

Phosphorylated extracellular signal-regulated kinase

p-ERK-IR:

p-ERK immunoreactive

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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 (24592764).

Conflict of interest

The authors do not have any conflict of interest.

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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, Noriko Kishimoto, Yuya Yamamoto, Kotaro Maruhama, Hiroki Tsuchiya & Tomosada Sugimoto

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

    Noriko Kishimoto, Yuya Yamamoto, Masahide Mizutani & Seiji Iida

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

    Ryuji Terayama, Kotaro Maruhama, Masahide Mizutani, Seiji Iida & Tomosada Sugimoto

  4. ASAHI Medical College at Okayama, Okayama, 700-0028, Japan

    Hiroki Tsuchiya

Authors
  1. Ryuji Terayama
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  2. Noriko Kishimoto
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  3. Yuya Yamamoto
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  4. Kotaro Maruhama
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  5. Hiroki Tsuchiya
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  6. Masahide Mizutani
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  7. Seiji Iida
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  8. Tomosada Sugimoto
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Correspondence to Ryuji Terayama.

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Terayama, R., Kishimoto, N., Yamamoto, Y. et al. Convergent Nociceptive Input to Spinal Dorsal Horn Neurons After Peripheral Nerve Injury. Neurochem Res 40, 438–445 (2015). https://doi.org/10.1007/s11064-014-1484-y

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  • DOI: https://doi.org/10.1007/s11064-014-1484-y

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