Protective effect of telmisartan against morphine-induced analgesic tolerance in mice

Elif Nur Barut; Seçkin Engin; Yeşim Kaya Yaşar; Mine Duman

Makale detayları

Protective effect of telmisartan against morphine-induced analgesic tolerance in mice

Yazarlar:

Elif Nur Barut | Seçkin Engin | Yeşim Kaya Yaşar | Mine Duman

Yayıncı:

Marmara University

Ana Başlıklar:

Basic Pharmacology

Dergi:

Journal of Research in Pharmacy Vol.28 Issue 4, pp.1079-1087

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001347025

pISSN:

2630-6344

Anahtar kelimeler:

Özet:

 Morphine tolerance is a serious clinical problem characterized by a decreased analgesic effect resulted from the long-term use of morphine with uncertain etiology and therapeutic interventions are limited. In this study, we aimed to investigate the effect of telmisartan in a mouse model of morphine-induced analgesic tolerance and the underlying mechanisms of its action. Morphine 10 mgkg was injected subcutaneously twice daily for five days. Mice were pretreated with Telmisartan TEL; 5 and 15 mgkg orally by gavage 30 min before each morphine injection. L-NAME 10 mgkg, L-arginine L-ARG,300 mgkg or N-acetylcysteine NAC, 50 mgkg was administered intraperitoneally 45 min prior to morphine. Analgesic efficacy was evaluated by hot-plate test on 1st, 3rd and 5th days, 60 min after morphine injection. Spinal cord samples of mice were used to examine the protein expressions of nNOS and iNOS by western blotting and total GSH content. Repeated morphine administration caused a significant decrease in analgesic efficacy, demonstrating the development of morphine tolerance. High-dose TEL treatment effectively prevented morphine-induced analgesic tolerance. L-ARG abolished the inhibitory effect of TEL on morphine tolerance, while L- NAME and NAC did not alter. GSH level and nNOS expression were decreased, as well as iNOS expression was increased in the spinal cords from morphine-tolerant mice. TEL 15 mgkg treatment prevented the decrease in GSH level and the increase in iNOS expression of spinal cords. TEL would be a potential therapeutic candidate in preventing morphine tolerance through its activity on antioxidant systems and, in part, on the nitric oxide pathway.

 Morphine tolerance is a serious clinical problem characterized by a decreased analgesic effect resulted from the long-term use of morphine with uncertain etiology and therapeutic interventions are limited. In this study, we aimed to investigate the effect of telmisartan in a mouse model of morphine-induced analgesic tolerance and the underlying mechanisms of its action. Morphine 10 mgkg was injected subcutaneously twice daily for five days. Mice were pretreated with Telmisartan TEL; 5 and 15 mgkg orally by gavage 30 min before each morphine injection. L-NAME 10 mgkg, L-arginine L-ARG,300 mgkg or N-acetylcysteine NAC, 50 mgkg was administered intraperitoneally 45 min prior to morphine. Analgesic efficacy was evaluated by hot-plate test on 1st, 3rd and 5th days, 60 min after morphine injection. Spinal cord samples of mice were used to examine the protein expressions of nNOS and iNOS by western blotting and total GSH content. Repeated morphine administration caused a significant decrease in analgesic efficacy, demonstrating the development of morphine tolerance. High-dose TEL treatment effectively prevented morphine-induced analgesic tolerance. L-ARG abolished the inhibitory effect of TEL on morphine tolerance, while L- NAME and NAC did not alter. GSH level and nNOS expression were decreased, as well as iNOS expression was increased in the spinal cords from morphine-tolerant mice. TEL 15 mgkg treatment prevented the decrease in GSH level and the increase in iNOS expression of spinal cords. TEL would be a potential therapeutic candidate in preventing morphine tolerance through its activity on antioxidant systems and, in part, on the nitric oxide pathway.

 Morphine tolerance is a serious clinical problem characterized by a decreased analgesic effect resulted from the long-term use of morphine with uncertain etiology and therapeutic interventions are limited. In this study, we aimed to investigate the effect of telmisartan in a mouse model of morphine-induced analgesic tolerance and the underlying mechanisms of its action. Morphine 10 mgkg was injected subcutaneously twice daily for five days. Mice were pretreated with Telmisartan TEL; 5 and 15 mgkg orally by gavage 30 min before each morphine injection. L-NAME 10 mgkg, L-arginine L-ARG,300 mgkg or N-acetylcysteine NAC, 50 mgkg was administered intraperitoneally 45 min prior to morphine. Analgesic efficacy was evaluated by hot-plate test on 1st, 3rd and 5th days, 60 min after morphine injection. Spinal cord samples of mice were used to examine the protein expressions of nNOS and iNOS by western blotting and total GSH content. Repeated morphine administration caused a significant decrease in analgesic efficacy, demonstrating the development of morphine tolerance. High-dose TEL treatment effectively prevented morphine-induced analgesic tolerance. L-ARG abolished the inhibitory effect of TEL on morphine tolerance, while L- NAME and NAC did not alter. GSH level and nNOS expression were decreased, as well as iNOS expression was increased in the spinal cords from morphine-tolerant mice. TEL 15 mgkg treatment prevented the decrease in GSH level and the increase in iNOS expression of spinal cords. TEL would be a potential therapeutic candidate in preventing morphine tolerance through its activity on antioxidant systems and, in part, on the nitric oxide pathway.

 Morphine tolerance is a serious clinical problem characterized by a decreased analgesic effect resulted from the long-term use of morphine with uncertain etiology and therapeutic interventions are limited. In this study, we aimed to investigate the effect of telmisartan in a mouse model of morphine-induced analgesic tolerance and the underlying mechanisms of its action. Morphine 10 mgkg was injected subcutaneously twice daily for five days. Mice were pretreated with Telmisartan TEL; 5 and 15 mgkg orally by gavage 30 min before each morphine injection. L-NAME 10 mgkg, L-arginine L-ARG,300 mgkg or N-acetylcysteine NAC, 50 mgkg was administered intraperitoneally 45 min prior to morphine. Analgesic efficacy was evaluated by hot-plate test on 1st, 3rd and 5th days, 60 min after morphine injection. Spinal cord samples of mice were used to examine the protein expressions of nNOS and iNOS by western blotting and total GSH content. Repeated morphine administration caused a significant decrease in analgesic efficacy, demonstrating the development of morphine tolerance. High-dose TEL treatment effectively prevented morphine-induced analgesic tolerance. L-ARG abolished the inhibitory effect of TEL on morphine tolerance, while L- NAME and NAC did not alter. GSH level and nNOS expression were decreased, as well as iNOS expression was increased in the spinal cords from morphine-tolerant mice. TEL 15 mgkg treatment prevented the decrease in GSH level and the increase in iNOS expression of spinal cords. TEL would be a potential therapeutic candidate in preventing morphine tolerance through its activity on antioxidant systems and, in part, on the nitric oxide pathway.

Makale detayları

Protective effect of telmisartan against morphine-induced analgesic tolerance in mice

Yazarlar: Elif Nur Barut | Seçkin Engin | Yeşim Kaya Yaşar | Mine Duman

Yayıncı: Marmara University

Ana Başlıklar: Basic Pharmacology

Dergi: Journal of Research in Pharmacy Vol.28 Issue 4, pp.1079-1087

Belge Tipi: Makale

Yayın Tarihi: 6/2025

Belge Dili: İngilizce

Document ID (Org No.): 2001347025

pISSN: 2630-6344

hot-plate test

mice

morphine tolerance

nitric oxide

telmisartan

Sayı

Yazarlar:

Elif Nur Barut | Seçkin Engin | Yeşim Kaya Yaşar | Mine Duman

Yayıncı:

Marmara University

Ana Başlıklar:

Basic Pharmacology

Dergi:

Journal of Research in Pharmacy Vol.28 Issue 4, pp.1079-1087

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001347025

pISSN:

2630-6344