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Peripheral nerve injury activates convergent nociceptive input to dorsal horn neurons from neighboring intact nerve

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Abstract

Previous studies demonstrated that peripheral nerve injury induced excessive nociceptive response of spinal cord dorsal horn neurons and such change has been proposed to reflect the development of neuropathic pain state. The aim of this study was to examine the spinal dorsal horn for convergence of nociceptive input to second-order neurons deafferented by peripheral nerve injury. Double immunofluorescence labeling for c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) was performed to detect convergent synaptic input to spinal dorsal horn neurons after the saphenous nerve injury. c-Fos expression and the phosphorylation of ERK were induced by noxious heat stimulation of the hindpaw and by electrical stimulation of the injured or uninjured saphenous nerve, respectively. Within the central terminal field of the saphenous nerve, the number of c-Fos protein-like immunoreactive (c-Fos-IR) cell profiles was significantly decreased at 3 days and returned to the control level by 14 days after the injury. p-ERK immunoreactive (p-ERK-IR) cell profiles were distributed in the central terminal field of the saphenous nerve, and the topographic distribution pattern and number of such p-ERK-IR cell profiles remained unchanged after the nerve injury. The time course of changes in the number of double-labeled cell profiles was similar to that of c-Fos-IR cell profiles after the injury. These results indicate that convergent primary nociceptive input through neighboring intact nerves contributes to increased responsiveness of spinal dorsal horn nociceptive neurons.

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Abbreviations

ANOVA:

Analysis of variance

CNS:

Central nervous system

DAB:

Diaminobenzidine

ES:

Electrical stimulation

c-Fos-IR:

c-Fos protein-like immunoreactive

MAPK:

Mitogen-activated protein kinase

PAP:

Peroxidase anti-peroxidase

p-ERK:

Phosphorylated extracellular signal-regulated kinase

p-ERK-IR:

p-ERK immunoreactive

PB:

Phosphate buffer

PBS:

Phosphate-buffered saline

SNI:

Saphenous nerve injury

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Acknowledgments

This study was supported by the Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (24592764).

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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, 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, 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

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

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Terayama, R., Yamamoto, Y., Kishimoto, N. et al. Peripheral nerve injury activates convergent nociceptive input to dorsal horn neurons from neighboring intact nerve. Exp Brain Res 233, 1201–1212 (2015). https://doi.org/10.1007/s00221-015-4203-2

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  • DOI: https://doi.org/10.1007/s00221-015-4203-2

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