Losartan treatment attenuates the development of neuropathic thermal hyperalgesia induced by peripheral nerve injury in rats

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F19%3A00503875" target="_blank" >RIV/67985823:_____/19:00503875 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1016/j.lfs.2019.02.008" target="_blank" >https://doi.org/10.1016/j.lfs.2019.02.008</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.lfs.2019.02.008" target="_blank" >10.1016/j.lfs.2019.02.008</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Losartan treatment attenuates the development of neuropathic thermal hyperalgesia induced by peripheral nerve injury in rats

Popis výsledku v původním jazyce

Aims: Neuroinflammatory changes in the central nervous system are widely involved in the initiation and maintenance of neuropathic pain after peripheral nerve injury. The present study investigated how losartan treatment may affect the development of neuropathic pain and neuroinflammation. Main methods: The effect of losartan treatment on the development of peripheral neuropathy was studied in L5 spinal nerve ligation (SNL) model in rats with systemic (100 mg/kg) or intrathecal (10 mu l/20 mu M solution) application of losartan. Electronic von Frey filament and plantar test were used to determine pain thresholds to mechanical and thermal stimulations. At the 7th post-operative day, CD68-positive cells in DRG and dorsal roots were quantified by immunohistochemistry and western blot analyses were used to compare the expression levels of neuroinflammatory markers in lumbar spinal cord (SC). Key findings: Our data confirmed the presence of SNL-evoked heat hyperalgesia and mechanical allodynia. Losartan application blocked the SNL-induced hypersensitivity to thermal stimuli but failed to prevent mechanical allodynia. No significant difference between systemic and i.t. administration of losartan was observed. Immunohistochemistry confirmed the presence of infiltrated macrophages in the ipsilateral DRG that was significantly attenuated with the losartan treatment. Western blot SC tissue analysis revealed that systemic treatment with losartan prevented SNL-induced upregulation of CCR2, TNF alpha, TNFR1, and OX42 while its effect on CCL2 and AT1R expression was not significant. Significance: Our results show that losartan treatment attenuates neuroinflammation and neuropathic pain after SNL. These effects of losartan represent an interesting direction for the development of novel treatments of peripheral neuropathy.

Název v anglickém jazyce

Losartan treatment attenuates the development of neuropathic thermal hyperalgesia induced by peripheral nerve injury in rats

Popis výsledku anglicky

Aims: Neuroinflammatory changes in the central nervous system are widely involved in the initiation and maintenance of neuropathic pain after peripheral nerve injury. The present study investigated how losartan treatment may affect the development of neuropathic pain and neuroinflammation. Main methods: The effect of losartan treatment on the development of peripheral neuropathy was studied in L5 spinal nerve ligation (SNL) model in rats with systemic (100 mg/kg) or intrathecal (10 mu l/20 mu M solution) application of losartan. Electronic von Frey filament and plantar test were used to determine pain thresholds to mechanical and thermal stimulations. At the 7th post-operative day, CD68-positive cells in DRG and dorsal roots were quantified by immunohistochemistry and western blot analyses were used to compare the expression levels of neuroinflammatory markers in lumbar spinal cord (SC). Key findings: Our data confirmed the presence of SNL-evoked heat hyperalgesia and mechanical allodynia. Losartan application blocked the SNL-induced hypersensitivity to thermal stimuli but failed to prevent mechanical allodynia. No significant difference between systemic and i.t. administration of losartan was observed. Immunohistochemistry confirmed the presence of infiltrated macrophages in the ipsilateral DRG that was significantly attenuated with the losartan treatment. Western blot SC tissue analysis revealed that systemic treatment with losartan prevented SNL-induced upregulation of CCR2, TNF alpha, TNFR1, and OX42 while its effect on CCL2 and AT1R expression was not significant. Significance: Our results show that losartan treatment attenuates neuroinflammation and neuropathic pain after SNL. These effects of losartan represent an interesting direction for the development of novel treatments of peripheral neuropathy.

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

2019

Kód důvěrnosti údajů

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

Název periodika

Life Sciences

ISSN

0024-3205

e-ISSN

—

Svazek periodika

220

Číslo periodika v rámci svazku

Mar 1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

147-155

Kód UT WoS článku

000458400900016

EID výsledku v databázi Scopus

2-s2.0-85061107249