PhD Scientific Days 2026

Poster Session 3.W - Pharmaceutical Sciences and Health Technologies

Investigating the Role of AT1 Receptor in Morphine-Induced Antinociceptive Tolerance

Előadó neve

Dr. Boldizsár, Imre

Neptune code

T9KTI0

Előadó munkahelye

Department of Pharmacology and Pharmacotherapy, Semmelweis University

Előadó telefonszáma

06205018280

Előadó e-mail címe

boldizsar.imre2@semmelweis.hu

Az előadás címe

Investigating the Role of AT1 Receptor in Morphine-Induced Antinociceptive Tolerance

Szerző(k) neve és munkahelye

Imre Boldizsár Jr^1,2, Judit Mária Kirchlechner-Farkas^1,2, Sarah Kadhim Abood^1,2, Yashar Chalabiani^1,2, Zita Puskár³, Dávid Árpád Karádi^1,2, Mahmoud Al-Khrasani^1,2, Kornél Király^1,2

1: Department of Pharmacology and Pharmacotherapy, Semmelweis University
2: Center for Pharmacology and Drug Research & Development, Semmelweis University
3: Department of Anatomy, Histology and Embryology, Semmelweis University

Bemutatás módja

Poszter

Szekció

Poster Session 3.W - Pharmaceutical Sciences and Health Technologies

Language of the presentation

English

Preferred session

Pharmaceutical Sciences and Health Technologies

Összefoglaló szövege

Introduction: Opioid analgesics are the cornerstones in the management of moderate to severe pain, however their effectiveness is hampered by side effects such as analgesic tolerance. Angiotensin II receptor type 1 (AT1) blockers (ARBs), particularly telmisartan, have been shown to alleviate chronic pain and delay the development of morphine tolerance. However, the effect of ARBs on opioid antinociceptive tolerance development, the localisation of AT1 in the spinal cord, and possible co-localisation of AT1 and μ-opioid receptor (MOR) remains to be fully elucidated.
Aims: To determine the extent to which ARB treatment influences morphine antinociceptive tolerance; explore the localisation of AT1 and its possible co-localisation with MOR in the spinal cord.
Methods: Male Wistar rats (180-250 g) were treated with different combination of subcutaneous morphine (31.08 μmol/kg), oral telmisartan (20 μmol/kg) or their respective vehicles for 9 days. On day 10, all animals were treated with different doses of morphine to construct dose-response curves (DRC) of morphine. The rat tail-flick assay was used to test the antinociceptive effect. After plotting the DRCs, animals were sacrificed, and their spinal cords were removed for further analysis. In the spinal dorsal horn (SDH) the fluorescent intensity of MOR was measured. To investigate the colocalization of AT1 and MOR, naïve rats were used. Histological sections were analysed using confocal microscopy.
Results: Chronic morphine administration for 9 days resulted in a rightward shift and a slight flattening in its DRC, indicating the development of morphine-induced antinociceptive tolerance. After the chronic co-administration of morphine and telmisartan, morphine retained its maximal effect in the investigated dose-range and a leftward shift was observed in the DRC. The fluorescent intensity of MOR in SDH did not differ between treatment groups. The AT1 was localised in the outer laminae of SDH and double -positive MOR+/AT1+ structures were also detected.
Conclusion: ARB treatment preserved the maximal effect of morphine and reduced the rightward shift of morphine’s DRC in an opioid tolerance model in vivo. Spinal MOR fluorescent intensity was unaffected by chronic treatment with morphine or ARB. AT1 localises mainly in the dorsal horn of the spinal cord in the proximity of MOR.
Funding: SE250+,TKP2021-EGA-25

University

Semmelweis University

Supervisor

Kornél Király

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

phd.section.field

in doctoral studies before complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

9069

Start

13:42

End

13:45