A New Rat Pain Model of Thrombus-Induced Ischemia

Abstract

Pathophysiology of peripheral ischemic pain has not been fully demonstrated since the proper animal model has not been established. We designed this study to develop a new thrombus-induced ischemic pain (TIIP) animal model mimicking human peripheral ischemic pain by using ferrous chloride (FeCl₂) in rats. Histological examination and Evans blue experiment revealed that the application of FeCl₂ onto the femoral artery produced an excessive thrombosis and ischemic condition in ipsilateral hind paw. Furthermore, ischemia-sensitive markers, such as hypoxia inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) were upregulated in the ipsilateral plantar muscles of FeCl₂-applied rats. The mechanical allodynia was induced in bilateral hind paws from 1 day after FeCl₂ application and sustained for 30 days. However, thermal threshold of bilateral hind paws did not change in this animal model. In conclusion, we have developed a novel animal model of TIIP, which is characterized by the development of bilateral mechanical allodynia, but not thermal hyperalgesia. Thus, we suggest that this TIIP model can be useful in investigating the pathophysiological mechanisms that underlie human peripheral ischemic pain.