Chronic IL-1β signaling potentiates voltage-dependent sodium currents in trigeminal nociceptive neurons

The proinflammatory cytokine interleukin-1 beta (IL-1 beta) mediates inflammation and hyperalgesia, although the underlying mechanisms remain elusive. To better understand such molecular and cellular mechanisms, we investigated how IL-1 beta modulates the total voltage-dependent sodium currents (I-Na) 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 beta. A brief exposure led to a 28% specific ( receptor-mediated) reduction of I-Na 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 I-Na was suppressed in the presence of selective inhibitors of protein kinase C and G-protein coupled signaling pathways, thereby suggesting that I-Na can be modulated through multiple pathways. In summary, the potentiation of I-Na through chronic IL-1 beta signaling in nociceptive sensory neurons may be a critical component of inflammatory-associated hyperalgesia.