Chronic IL-1 Signaling Potentiates Voltage-Dependent Sodium Currents in Trigeminal Nociceptive Neurons

Liu, Lieju, T. M. Yang, Wolfgang Liedtke, and S. A. Simon. Chronic IL-1 signaling potentiates voltage-dependent sodium currents in trigeminal nociceptive neurons. J Neurophysiol 95: 1478–1490, 2006. First published November 30, 2005; doi:10.1152/jn.00509.2005. The proinflammatory cytokine interleukin-1 (IL-1 ) mediates inflammation and hyperalgesia, although the underlying mechanisms remain elusive. To better understand such molecular and cellular mechanisms, we investigated how IL-1 modulates the total voltage-dependent sodium currents (INa) and its tetrodotoxin-resistant (TTX-R) component in capsaicin-sensitive trigeminal nociceptive neurons, both after a brief (5-min) and after a chronic exposure (24-h) of 20 ng/ml IL-1 . A brief exposure led to a 28% specific (receptor-mediated) reduction of INa in these neurons, which were found to contain type I IL-1 receptors (IL-1RI ) on both their soma and nerve endings. In marked contrast, after a 24-h exposure, the total sodium current was specifically increased by 67%, without significantly affecting the TTX-R component. This potentiation of INa was suppressed in the presence of selective inhibitors of protein kinase C and G-protein– coupled signaling pathways, thereby suggesting that INa can be modulated through multiple pathways. In summary, the potentiation of INa through chronic IL-1 signaling in nociceptive sensory neurons may be a critical component of inflammatory-associated hyperalgesia.