Direct evidence for spinal cord microglia in the development of a neuropathic pain-like state in mice.
The present study was undertaken to further investigate the role of glial cells in the development of the neuropathic pain-like state induced by sciatic nerve ligation in mice. At 7 days after sciatic nerve ligation, the immunoreactivities (IRs) of the specific astrocyte marker glial fibrillary acidic protein (GFAP) and the specific microglial marker OX-42, but not the specific oligodendrocyte marker O4, were increased on the ipsilateral side of the spinal cord dorsal horn in nerve-ligated mice compared with that on the contralateral side. Furthermore, a single intrathecal injection of activated spinal cord microglia, but not astrocytes, caused thermal hyperalgesia in naive mice. Furthermore, 5-bromo-2'-deoxyuridine (BrdU)-positive cells on the ipsilateral dorsal horn of the spinal cord were significantly increased at 7 days after nerve ligation and were highly co-localized with another microglia marker, ionized calcium-binding adaptor molecule 1 (Iba1), but neither with GFAP nor a specific neural nuclei marker, NeuN, in the spinal dorsal horn of nerve-ligated mice. The present data strongly support the idea that spinal cord astrocytes and microglia are activated under the neuropathic pain-like state, and that the proliferated and activated microglia directly contribute to the development of a neuropathic pain-like state in mice.
Narita
Minoru
M
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan. narita@hoshi.ac.jp
Yoshida
Takuya
T
Nakajima
Mayumi
M
Narita
Michiko
M
Miyatake
Mayumi
M
Takagi
Tomoe
T
Yajima
Yoshinori
Y
Suzuki
Tsutomu
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001253:Astrocytes / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D039481:CD11b Antigen; D002135:Calcium-Binding Proteins / Q000378:metabolism; D049109:Cell Proliferation; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D006930:Hyperalgesia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008026:Ligation; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008840:Microfilament Proteins; D017628:Microglia / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D008911:Minocycline / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009437:Neuralgia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009687:Nuclear Proteins / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020426:Sciatic Neuropathy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016378:Tissue Transplantation
C100745:Aif1 protein, rat; D000900:Anti-Bacterial Agents; D015415:Biomarkers; D039481:CD11b Antigen; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; C509295:ITGAM protein, human; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D008911:Minocycline