Characterization of cell proliferation in rat spinal cord following peripheral nerve injury and the relationship with neuropathic pain.
Glial activation is a typical response of the central nervous system to nerve injury. In the current investigation, we characterized the temporal and spatial pattern of glial proliferation, one of the most conspicuous features of glial activation, in relation to nerve injury-induced neuropathic pain. Using bromodeoxyuridine (BrdU) as a mitotic marker, we analyzed cell proliferation in the spinal cord, identified the phenotype of dividing cells, traced their fate, and correlated these phenomena with behavioural assays of the neuropathic pain syndrome. Our results demonstrated that peripheral nerve injury induced an early and transient cell proliferation, on the spinal cord ipsilateral to the nerve lesion which peaked at day 3 post-surgery. The majority of the proliferating cells were Iba-1(+) microglia, together with some NG2(+) oligodendrocyte progenitors, and GFAP(+) astrocytes. These newly generated cells continued to divide over time with the response peaking at day 14 post-injury. Microglia were always the predominant phenotype which made up over 60% of activated microglia derived from this newly generated cell population. There was a close temporal correlation between microglial proliferation in the spinal cord dorsal horn and the abnormal pain responses, suggesting a contribution of the new microglia to the genesis of the neuropathic pain symptoms.
Echeverry
Stefania
S
Unité de Neurobiologie Cellulaire, Centre de Recherche Université Laval Robert-Giffard, Université Laval, 2601, Chemin de la Canardière, Québec, Canada.
Shi
Xiang Qun
XQ
Zhang
Ji
J
D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D049109:Cell Proliferation; D007839:Functional Laterality; D008161:Lumbosacral Region; D008297:Male; D008840:Microfilament Proteins; D017628:Microglia / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009437:Neuralgia / Q000209:etiology* / Q000473:pathology; D010147:Pain Measurement / Q000379:methods; D010523:Peripheral Nervous System Diseases / Q000150:complications* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology*; D013997:Time Factors
C100745:Aif1 protein, rat; D039481:CD11b Antigen; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D001973:Bromodeoxyuridine