Inhibitors of G-proteins and protein kinases reduce the sensitization to mechanical stimulation and the desensitization to heat of spinothalamic tract neurons induced by intradermal injection of capsaicin in the primate

Abstract

 Intradermal injection of capsaicin results in sensitization of spinothalamic tract cells to brushing and pressure applied to the cutaneous receptive field in anesthetized monkeys. A significant increase in background activity also occurs immediately after capsaicin injection that lasts for at least 2 h. A 40–50% decrease in the response to noxious heat stimuli is also observed following capsaicin injection. This study investigated the spinal role of second messengers by extracellularly recording from spinothalamic tract cells and delivering inhibitors of second messenger pathways to the spinal cord by microdialysis. Blockade of protein kinases with the general protein kinase inhibitor, H7 (5.0 mM, n = 6), reduced the sensitization of the cells to brush and pressure. Blockade of protein kinase C with NPC15437 (10.0 mM, n = 10) reduced the increased background activity and the increased responses to brush. Blockade of protein kinase A with H89 (0.01 mM, n = 9) was most effective. H89 reduced the background activity, the increased responses to brush and press, and reversed the decreased response to noxious heat stimuli. Blockade of G-proteins with the general G-protein inhibitor, GDP-β-S (1.0 mM, n = 9), reduced the background activity and the responses to brush and pressure without affecting the decreased response to heat. Thus, multiple intracellular messengers appear to be involved in the processing of central sensitization induced by activation of C-fibers following intradermal injection of capsaicin.