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

0489199 - FGÚ 2019 RIV US eng J - Journal Article
Torres-Pérez, J. V. - Adámek, Pavel - Paleček, Jiří - Vizcaychipi, M. - Nagy, I. - Varga, A.
The NA(v)1.7 blocker protoxin II reduces burn injury-induced spinal nociceptive processing.
Journal of Molecular Medicine-Jmm. Roč. 96, č. 1 (2018), s. 75-84. ISSN 0946-2716. E-ISSN 1432-1440
R&D Projects: GA ČR(CZ) GA15-11138S; GA MŠMT(CZ) LQ1604; GA MŠMT(CZ) LH15279; GA MŠMT(CZ) ED1.1.00/02.0109
Institutional support: RVO:67985823
Keywords : pain * p-ERK1/2 * primary sensory neuron * p-S10H3 * spinal cord
OECD category: Neurosciences (including psychophysiology
Impact factor: 4.746, year: 2018

Controlling pain in burn-injured patients poses a major clinical challenge. Recent findings suggest that reducing the activity of the voltage-gated sodium channel Na(v)1.7 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 Na(v)1.7 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 Na(v)1.7-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 Na(v)1.7 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 Na(v)1.7 blockers should be considered to control pain in burn injury.
Permanent Link: http://hdl.handle.net/11104/0283660