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

0503875 - FGÚ 2020 RIV GB eng J - Journal Article
Kalynovska, Nataliia - Diallo, Michael - Paleček, Jiří
Losartan treatment attenuates the development of neuropathic thermal hyperalgesia induced by peripheral nerve injury in rats.
Life Sciences. Roč. 220, Mar 1 (2019), s. 147-155. ISSN 0024-3205. E-ISSN 1879-0631
R&D Projects: GA ČR GA18-09853S; GA MŠMT(CZ) ED1.1.00/02.0109
Institutional support: RVO:67985823
Keywords : neuropathic pain * neuroinflammation * DRG * Losartan * SNL * macrophage
OECD category: Neurosciences (including psychophysiology
Impact factor: 3.647, year: 2019
Method of publishing: Limited access
https://doi.org/10.1016/j.lfs.2019.02.008

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.
Permanent Link: http://hdl.handle.net/11104/0295647