Central sensitization: Effects of a specific protein phosphatase on long lasting central sensitization following injection of capsaicin

Abstract

Kinases and phosphatases catalyze opposing reactions of phosphorylation and dephosphorylation, which may modulate the function of crucial proteins in the nervous system. This is an important mechanism in the regulation of cellular signal transduction and metabolism in nociceptive neurons. Fostriecin, a specific inhibitor of serine/threonine protein phosphatase type 2A (PP2A), may contribute to the process of long lasting central sensitization of nociceptive neurons in the spinal cord by causing protein hyperphosphorylation. This study was designed to assess the role of PP2A in the spinal cord in the electrophysiological manifestations induced by intradermal injection of capsaicin in rats. A microdialysis fiber was implanted in the spinal cord dorsal horn for ACSF and fostriecin pre- or postreatment. Central sensitization was initiated by injection of capsaicin into the plantar surface of the left paw. In ACSF pretreated animals, the responses to innocuous and noxious stimuli following capsaicin injection increased 15 min after injection and mostly recovered by 60 min later. Compared to the control animals, pre- or postreatment with the phosphatase inhibitor, fostriecin, into the spinal cord dorsal horn enhanced the increased responses by making the responses last more than 3 hours. These results demonstrate that fostriecin potentiates central sensitization of nociceptive transmission in the spinal cord following capsaicin injection and indicate that PP2A may be involved in determining the duration of capsaicin-induced central sensitization. Supported by NIH grants NS09743 & NS11255.