title: Activated microglia contribute to convergent nociceptive inputs to spinal dorsal horn neurons and the development of neuropathic pain.
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.
authors.affiliation: 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.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Ryuji
authors.initials: R
authors.lastname: Terayama
authors.forename: Noriko
authors.initials: N
authors.lastname: Kishimoto
authors.forename: Kotaro
authors.initials: K
authors.lastname: Maruhama
authors.forename: Masahide
authors.initials: M
authors.lastname: Mizutani
authors.forename: Seiji
authors.initials: S
authors.lastname: Iida
authors.forename: Tomosada
authors.initials: T
authors.lastname: Sugimoto
mesh_terms: D000818:Animals; D008297:Male; D017628:Microglia / Q000378:metabolism*; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism*; D010147:Pain Measurement / Q000379:methods*; D020671:Posterior Horn Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013979:Tibial Nerve / Q000293:injuries* / Q000378:metabolism*