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

Content Provider	Springer Nature Link
Author	Yamamoto, Yuya Terayama, Ryuji Kishimoto, riko Maruhama, Kotaro Mizutani, Masahide Iida, Seiji Sugimoto, Tomosada
Copyright Year	2015
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.
Starting Page	1000
Ending Page	1012
Page Count	13
File Format	PDF
ISSN	03643190
Journal	Neurochemical Research
Volume Number	40
Issue Number	5
e-ISSN	15736903
Language	English
Publisher	Springer US
Publisher Date	2015-03-18
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Microglia Minocycline Nerve injury c-Fos ERK Spinal dorsal horn Neurosciences Neurochemistry Biochemistry Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Cellular and Molecular Neuroscience

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

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