Telmisartan Is a Promising Agent for Managing Neuropathic Pain and Delaying Opioid Analgesic Tolerance in Rats

David Karádi, Anna Rita Galambos, Péter P. Lakatos, Joost Apenberg, Sarah K. Abbood, Mihály Balogh, Kornél Király, Pál Riba, Nariman Essmat, Edina Szűcs, Sándor Benyhe, Zoltán V. Varga, Éva Szökő, Tamás Tábi, Mahmoud Al-Khrasani*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Article number7970
Number of pages18
JournalInternational Journal of Molecular Sciences
Issue number9
Publication statusPublished - May-2023


  • angiotensin receptor type 1
  • losartan
  • morphine
  • neuropathic pain
  • neuropathy
  • opioid tolerance
  • opioids
  • RAS
  • telmisartan

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