The lumbar spinal cord glial cells actively modulate subcutaneous formalin induced hyperalgesia in the rat.
We investigated the response and relationship of glial cells and neurons in lumbar spinal cord to hyperalgesia induced by the unilateral subcutaneous formalin injection into the hindpaw of rats. It was demonstrated that Fos/NeuN immunoreactive (-IR) neurons, glial fibrillary acidic protein (GFAP)-IR astrocytes and OX42-IR microglia were distributed in dorsal horn of lumbar spinal cord, predominantly in the superficial layer. In the time-course studies, GFAP-IR astrocytes were firstly detected, OX42-IR microglia were sequentially observed, Fos/NeuN-IR neurons were found slightly late. Immunoelectron microscopy studies established that many heterotypic gap junctions (HGJs), which consisting of Cx43-IR astrocytic process on one side and Cx32-IR dendrite on the other side, were present in superficial layer of dorsal horn. Ninety-one HGJs were found in 100 areas of experimental rats and occupied 91%, while only 39% HGJs were found in control rats. In experimental rats pretreated with intrathecal (i.t.) application of the carbenoxolone (a gap junction blocker) or fluorocitrate (a glial metabolic inhibitor), the paw withdrawal thermal latency was prolonged than those application of the sterile saline (i.t.). It suggests that spinal cord glial cells may play an important role for modulation of hyperalgesia induced by noxious stimuli through HGJs which located between astrocytes and neurons.
Qin
Ming
M
Institute of Neurosciences, The Fourth Military Medical University, Changle West Road, Xi'an 710032, PR China.
Wang
Jing-Jie
JJ
Cao
Rong
R
Zhang
Hui
H
Duan
Li
L
Gao
Bei
B
Xiong
Ying-Fei
YF
Chen
Liang-Wei
LW
Rao
Zhi-Ren
ZR
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000648:ultrastructure; D015415:Biomarkers / Q000378:metabolism; D039481:CD11b Antigen; D002229:Carbenoxolone / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002951:Citrates / Q000494:pharmacology; D017630:Connexins / Q000378:metabolism; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D017628:Microglia / Q000378:metabolism* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D010147:Pain Measurement / Q000187:drug effects; D020671:Posterior Horn Cells / Q000378:metabolism* / Q000648:ultrastructure; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D039481:CD11b Antigen; D002951:Citrates; D017630:Connexins; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; C509295:ITGAM protein, human; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D016760:Proto-Oncogene Proteins c-fos; C007744:fluorocitrate; D002229:Carbenoxolone