Activated Microglia Contribute to Convergent Nociceptive Inputs to Spinal Dorsal Horn Neurons and the Development of Neuropathic Pain

Yuya Yamamoto, Ryuji Terayama, Noriko Kishimoto, Kotaro Maruhama, Masahide Mizutani, Seiji Iida, Tomosada Sugimoto

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The activation of microglia in the spinal dorsal horn following peripheral nerve injury has been reported previously, and this change has been proposed to contribute to the development of a neuropathic pain state. We recently demonstrated that peripheral nerve injury activated convergent nociceptive inputs to spinal dorsal horn neurons. The present study was designed to further examine the role of microglia in the activation of convergent nociceptive inputs as well as development of a neuropathic pain state after peripheral nerve injury. Tibial nerve injury initially induced hyposensitivity at 3 days post-injury, and this was followed by hypersensitivity to tactile and thermal stimuli at 14 days. The intraperitoneal administration of minocycline (30 mg/kg), an inhibitor of microglial activation, for 8 days starting on the day of surgery prevented increases in OX-42 immunofluorescence labeling in the spinal dorsal horn and the development of tactile and thermal hypersensitivity at 14 days post-injury. The same minocycline treatment (day 0–7) also reduced the nerve injury-induced convergence of nociceptive inputs to spinal dorsal horn neurons, as revealed by double immunofluorescence labeling for c-Fos induced by noxious heat stimulation of the hindpaw and phosphorylated extracellular signal-regulated kinase induced by electrical stimulation of the injured tibial nerve. However, the administration of minocycline for 8 days starting 7 days after surgery did not prevent nerve injury-induced microglial activation, convergent nociceptive inputs, or tactile and thermal hypersensitivity. These results suggest that microglial activation in the early stage following peripheral nerve injury plays an important role in the anomalous convergence of nociceptive signals to spinal dorsal horn neurons and the development of neuropathic pain.

Original languageEnglish
Pages (from-to)1000-1012
Number of pages13
JournalNeurochemical Research
Volume40
Issue number5
DOIs
Publication statusPublished - May 1 2015

Fingerprint

Posterior Horn Cells
Microglia
Neuralgia
Peripheral Nerve Injuries
Neurons
Chemical activation
Minocycline
Touch
Hot Temperature
Wounds and Injuries
Tibial Nerve
Hypersensitivity
Surgery
Labeling
Fluorescent Antibody Technique
Extracellular Signal-Regulated MAP Kinases
Ambulatory Surgical Procedures
Electric Stimulation

Keywords

  • c-Fos
  • ERK
  • Microglia
  • Minocycline
  • Nerve injury
  • Spinal dorsal horn

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Biochemistry

Cite this

Activated Microglia Contribute to Convergent Nociceptive Inputs to Spinal Dorsal Horn Neurons and the Development of Neuropathic Pain. / Yamamoto, Yuya; Terayama, Ryuji; Kishimoto, Noriko; Maruhama, Kotaro; Mizutani, Masahide; Iida, Seiji; Sugimoto, Tomosada.

In: Neurochemical Research, Vol. 40, No. 5, 01.05.2015, p. 1000-1012.

Research output: Contribution to journalArticle

Yamamoto, Yuya ; Terayama, Ryuji ; Kishimoto, Noriko ; Maruhama, Kotaro ; Mizutani, Masahide ; Iida, Seiji ; Sugimoto, Tomosada. / Activated Microglia Contribute to Convergent Nociceptive Inputs to Spinal Dorsal Horn Neurons and the Development of Neuropathic Pain. In: Neurochemical Research. 2015 ; Vol. 40, No. 5. pp. 1000-1012.
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