Impact of Duration and Severity of Persistent Pain on Programmed Cell Death

Abstract

Programmed cell death is a highly regulated form of cell death, mostly distinguished by the activation of a family of cystein-aspartate proteases (caspases) that cleave various proteins resulting in morphological and biochemical changes characteristic of this form of cell death. Several recent studies have addressed the role of programmed cell death in inflammatory and chronic pain states. Caspase-3 plays a central role in mediating nuclear programmed cell death including chromatin condensation and DNA fragmentation as well as cell blebbing. The aims of this study were to investigate the effect of duration and severity of persistent pain on the induction of programmed cell death. Formalin was administered subcutaneously in the Wistar rat hind paws for 1, 4 or 7 consecutive days, and then the activity of caspase-3 was measured in both the rat liver and brain cells. Morphological changes characterizing programmed cell death were also studied using the Sigma’s Apoptosis Detection kit, Annexin V-Cy3. Our findings showed that caspase-3 activity and apoptotic phenotype significantly increased in liver but not brain cells following the increase in duration and severity of formalin induced persistent pain.