The NA v 1.7 blocker protoxin II reduces burn injury-induced spinal nociceptive processing

Controlling pain in burn-injured patients poses a major clinical challenge. recent findings suggest that reducing the activity of the voltage-gated sodium channel nav1.7 in primary sensory neurons could provide improved pain control in burn-injured patients. here, we report that partial thickness scalding-type burn injury on the rat paw upregulates nav1.7 expression in primary sensory neurons 3 h following injury. the injury also induces upregulation in phosphorylated cyclic adenosine monophosphate response element-binding protein (p-creb), a marker for nociceptive activation in primary sensory neurons. the upregulation in p-creb occurs mainly in nav1.7-immunopositive neurons and exhibits a peak at 5 min and, following a decline at 30 min, a gradual increase from 1 h post-injury. the nav1.7 blocker protoxin ii (protxii) or morphine injected intraperitoneally 15 min before or after the injury significantly reduces burn injury-induced spinal upregulation in phosphorylated serine 10 in histone h3 and phosphorylated extracellular signal-regulated kinase 1/2, which are both markers for spinal nociceptive processing. further, protxii significantly reduces the frequency of spontaneous excitatory post-synaptic currents in spinal dorsal horn neurons following burn injury. together, these findings indicate that using nav1.7 blockers should be considered to control pain in burn injury. • burn injury upregulates nav1.7 expression in primary sensory neurons. • burn injury results in increased activity of nav1.7-expressing primary sensory neurons. • inhibiting nav1.7 by protoxin ii reduces spinal nociceptive processing. • nav1.7 represents a potential target to reduce pain in burn injury.