Chronic IL-1beta signaling potentiates voltage-dependent sodium currents in trigeminal nociceptive neurons.
The proinflammatory cytokine interleukin-1beta (IL-1beta) mediates inflammation and hyperalgesia, although the underlying mechanisms remain elusive. To better understand such molecular and cellular mechanisms, we investigated how IL-1beta 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-1beta. 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-1beta signaling in nociceptive sensory neurons may be a critical component of inflammatory-associated hyperalgesia.
Liu
Lieju
L
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA. Lieju@neuro.duke.edu
Yang
T M
TM
Liedtke
Wolfgang
W
Simon
S A
SA
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007375:Interleukin-1 / Q000008:administration & dosage* / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000502:physiology*
D007375:Interleukin-1; D015222:Sodium Channels; D012964:Sodium