Az orvos-, egészségtudományi- és gyógyszerészképzés tudományos műhelyeinek fejlesztése(EFOP-3.6.3-VEKOP-16-2017-00009)
Támogató: EFOP-VEKOP
(TKP2021-EGA-25)
Despite the large arsenal of analgesic medications, neuropathic pain (NP) management
is not solved yet. Angiotensin II receptor type 1 (AT1) has been identified as a potential
target in NP therapy. Here, we investigate the antiallodynic effect of AT1 blockers
telmisartan and losartan, and particularly their combination with morphine on rat
mononeuropathic pain following acute or chronic oral administration. The impact of
telmisartan on morphine analgesic tolerance was also assessed using the rat tail-flick
assay. Morphine potency and efficacy in spinal cord samples of treated neuropathic
animals were assessed by [35S]GTPγS-binding assay. Finally, the glutamate content
of the cerebrospinal fluid (CSF) was measured by capillary electrophoresis. Oral telmisartan
or losartan in higher doses showed an acute antiallodynic effect. In the chronic treatment
study, the combination of subanalgesic doses of telmisartan and morphine ameliorated
allodynia and resulted in a leftward shift in the dose–response curve of morphine
in the [35S]GTPγS binding assay and increased CSF glutamate content. Telmisartan delayed
morphine analgesic-tolerance development. Our study has identified a promising combination
therapy composed of telmisartan and morphine for NP and opioid tolerance. Since telmisartan
is an inhibitor of AT1 and activator of PPAR-γ, future studies are needed to analyze
the effect of each component.
