A Pan-Caspase Inhibitor Reduces Myocyte Apoptosis and Neuropathic Pain in Rats with Chronic Constriction Injury of the Sciatic Nerve

Abstract

Chronic constriction injury is a widely used model for neuropathic pain in rats. It presents with symptoms resembling human neuropathic pain, such as spontaneous pain, hyperalgesia, and allodynia. Recently, myocyte apoptosis was found in neuropathic rats as a possible promoter of pain and motor dysfunction. Our aim in this study was to demonstrate whether muscle cell apoptosis contributes to neuropathic pain in this animal model. To clarify this issue, we examined pain, nutritive perfusion, and inflammation in muscle tissue as well as myocyte apoptosis in rats with neuropathic pain established by chronic constriction injury of the sciatic nerve. Animals received either the pan-caspase inhibitor zVAD (OMe)-fmk (n = 5) or equivalent volumes of vehicle (n = 6). Sham-operated rats served as controls (n = 6). At day 4 after nerve ligation, there were no signs of perfusion failure or muscle tissue inflammation in all experimental groups. However, animals treated with the vehicle had marked myocyte apoptosis, which was found almost completely blocked in zVA-Dtreated animals. The zVA-Dtreated animals presented with a significant reduction of pain upon heat, cold, and mechanical stimulation comparable with values found in sham controls. Myocyte apoptosis possibly contributes to thermal and mechanical allodynia in this experimental model for neuropathic pain. The development of neuropathic pain symptoms did not depend on disturbances in microcirculation or muscle tissue inflammation.