[P3-0787] Cold-gated ion channels involve in cold allodynia in a new rat model of peripheral arterial disease
Keywords:peripheral arterial disease（PAD）, cold allodynia, TRPA1
【Purpose】
Patients with peripheral arterial disease（PAD）often suffer from peripheral hypersensitivity to cold stimulation which precedes chronic ischemia-induced pain. TASC II, guideline for the management of PAD, recommended the supervised physical exercise for the treatment, however, pain induced by cold stimulus interferes with such a therapeutic exercise. Therefore, it is important to understand the pathophysiology of cold hypersensitivity, of which is still unknown due to the lack of an adequate animal model. To demonstrate mechanisms underlying cold allodynia associated with PAD, we investigated the role of ion channels in a newly developed rat model of PAD.
【Methods】
Under sodium pentobarbital anesthesia, the left common iliac and iliolumbar arteries were ligated respectively, through a midline laparotomy（PAD rats）. Sham rats were exposed the arteries without ligation under anesthesia. Von Frey test, plantar test, and acetone test were performed, respectively. Alteration of paw withdrawal response to cold temperature were also examined. Histological examination of hindpaw skin was performed on day 4 and 10 after the arterial ligation. Effects of selective antagonist to cold-gated ion channels transient receptor potential melastatin 8（TRPM8）, and transient receptor potential ankyrin 1（TRPA1）channels, were evaluated on behavioral responses to cold stimulus.
【Results】
Mechanical allodynia was observed for 7 days and cold allodynia was observed 7 through 14 days after ligation. Intraplantar injection of the antagonists against TRPA1 suppressed cold allodynia in PAD rats.
【Discussion】
We have been able to develop an animal model of cold allodynia which preceded chronic ischemia-induced pain by arterial ligations in the rat. TRPA1 may play an important role in developing cold allodynia associated with PAD.
Patients with peripheral arterial disease（PAD）often suffer from peripheral hypersensitivity to cold stimulation which precedes chronic ischemia-induced pain. TASC II, guideline for the management of PAD, recommended the supervised physical exercise for the treatment, however, pain induced by cold stimulus interferes with such a therapeutic exercise. Therefore, it is important to understand the pathophysiology of cold hypersensitivity, of which is still unknown due to the lack of an adequate animal model. To demonstrate mechanisms underlying cold allodynia associated with PAD, we investigated the role of ion channels in a newly developed rat model of PAD.
【Methods】
Under sodium pentobarbital anesthesia, the left common iliac and iliolumbar arteries were ligated respectively, through a midline laparotomy（PAD rats）. Sham rats were exposed the arteries without ligation under anesthesia. Von Frey test, plantar test, and acetone test were performed, respectively. Alteration of paw withdrawal response to cold temperature were also examined. Histological examination of hindpaw skin was performed on day 4 and 10 after the arterial ligation. Effects of selective antagonist to cold-gated ion channels transient receptor potential melastatin 8（TRPM8）, and transient receptor potential ankyrin 1（TRPA1）channels, were evaluated on behavioral responses to cold stimulus.
【Results】
Mechanical allodynia was observed for 7 days and cold allodynia was observed 7 through 14 days after ligation. Intraplantar injection of the antagonists against TRPA1 suppressed cold allodynia in PAD rats.
【Discussion】
We have been able to develop an animal model of cold allodynia which preceded chronic ischemia-induced pain by arterial ligations in the rat. TRPA1 may play an important role in developing cold allodynia associated with PAD.