The NAv1.7 blocker protoxin II reduces burn injury-induced spinal nociceptive processing

Torres-Perez, J. V. and Adamek, P. and Palecek, J. and Vizcaychipi, M. and Nagy, István and Varga, Angelika (2018) The NAv1.7 blocker protoxin II reduces burn injury-induced spinal nociceptive processing. JOURNAL OF MOLECULAR MEDICINE-JMM, 96 (1). pp. 75-84. ISSN 0946-2716

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Abstract

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. KEY MESSAGES: * 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.

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