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Localization and function of insulin-like growth factor 1 in dorsal root ganglia in a rat disc herniation model
Bunji Takayama1, Miho Sekiguchi, Shoji Yabuki
1Department of Orthopedic Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan.
Study Design:
we investigated the localization of insulin-like growth factor 1 (IGF-1) using immunohistochemistry and the effects of small interfering RNA (siRNA) on IGF-1 in dorsal root ganglions (DRG) in a rat lumbar disc herniation (LDH) model.
Objective:
to determine the localization and function of IGF-1 in DRG of an experimental model of LDH.
Summary Of Background Data:
mechanical compression and chemical irritation are 2 major causative factors of radiculopathy in LDH. IGF-1, Ccnd1, Cdc2a, and CyclinA2 genes have been shown to be significantly upregulated in the mechanical model, but not in the chemical model. However, the localization and function of IGF-1 in DRG remain unknown in the mechanical compression animals.
Methods:
twenty-six adult female Sprague-Dawley rats were used in this study. A mechanical compression model was prepared by inserting a stainless rod. The rod was not inserted in the sham model. Expression of IGF-1 and Neuronal Nucli (NeuN) or glial fibrillary acidic protein was determined using double-fluorescence 7 days after mechanical compression (n = 5). Rats were randomly separated into 3 groups for the siRNA study (n = 7 in each group): (1) vehicle group; (2) siRNA group; and (3) sham group. The mechanical withdrawal threshold of the plantar food pad was examined using von Frey filaments for 35 days.
Results:
IGF-1 was localized particularly in the neuronal cell body, and revealed that it colocalized with NeuN but not with glial fibrillary acidic protein. The threshold was reduced in the vehicle and siRNA groups compared with the sham group. The threshold of the siRNA group significantly recovered from reduction compared with the vehicle group at 5 days after surgery, and this effect persisted throughout the experimental period. CONCLUSION.: IGF-1 was localized with neuronal cell bodies in DRG. IGF-1 knockdown caused a reduction in mechanical allodynia. The upregulation of IGF-1 might be a key factor in painful radiculopathy induced by mechanical factors.
