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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F18%3A00489199" target="_blank" >RIV/67985823:_____/18:00489199 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/18:10372377

Výsledek na webu

<a href="http://dx.doi.org/10.1007/s00109-017-1599-0" target="_blank" >http://dx.doi.org/10.1007/s00109-017-1599-0</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00109-017-1599-0" target="_blank" >10.1007/s00109-017-1599-0</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Molecular Medicine-Jmm

ISSN

0946-2716

e-ISSN

—

Svazek periodika

96

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

75-84

Kód UT WoS článku

000419131300008

EID výsledku v databázi Scopus

2-s2.0-85031925522