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Updated: Aug 1, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Morphine modulates inducible nitric oxide synthase expression and reduces pulmonary oedema induced by
Mustafa Comert1, Emine Yilmaz Sipahi, Huseyin Ustun
1Department of General Surgery, Faculty of Medicine, Zonguldak Karaelmas University, Zonguldak, Turkey.
Abstract:
This study was designed to investigate the possible participation of morphine in pulmonary oedema induced by alpha-naphthylthiourea (ANTU), which is a well-known noxious chemical agent in the lung. Injection of ANTU (15 mg/kg i.p.) produced pulmonary oedema as indicated by an increase in lung weight/body weight ratio and pleural effusion reaching a maximum within 4 h in rat. Administration of morphine prior to ANTU significantly inhibited to pulmonary oedema with a dose-dependent manner. The protective effect of morphine is prevented by peripheral opioid receptor antagonist, naloxone methiodide. ANTU-treated rats were shown positive by inducible nitric oxide synthase immunohistochemical staining. There was no staining in the control group. On the other hand, the degree of staining was markedly reduced in tissue sections by morphine. These results suggest that previous administration of subcutaneous morphine has preventive effect on ANTU-induced pulmonary inflammatory reaction and its effect mediated via peripheral opioid receptors. Application of naloxone with ANTU has no effect on the lung parameters indicating that endogenous opioids do not modulate ANTU-induced damage.
Insights
Morphine prevents lung injury caused by alpha-naphthylthiourea (ANTU) by acting on peripheral opioid receptors. This protective effect against ANTU-induced pulmonary edema and inflammation was dose-dependent and blocked by naloxone.
Area of Science:
- Pharmacology
- Toxicology
- Pulmonary Medicine
Background:
- Alpha-naphthylthiourea (ANTU) is a chemical agent known to induce pulmonary edema.
- The precise mechanisms underlying ANTU-induced lung injury are not fully understood.
Purpose of the Study:
- To investigate the role of morphine in preventing alpha-naphthylthiourea (ANTU)-induced pulmonary edema.
- To explore the involvement of peripheral opioid receptors in this protective effect.
Main Methods:
- Rats were injected with ANTU to induce pulmonary edema.
- Morphine was administered prior to ANTU, and its effects were assessed.
- Naloxone methiodide, an opioid receptor antagonist, was used to investigate the mechanism.
- Inducible nitric oxide synthase (iNOS) expression was examined using immunohistochemistry.
Main Results:
- ANTU injection significantly increased lung weight/body weight ratio and caused pleural effusion.
- Pre-treatment with morphine dose-dependently inhibited ANTU-induced pulmonary edema.
- The protective effect of morphine was reversed by naloxone methiodide.
- Morphine administration reduced the expression of inducible nitric oxide synthase (iNOS) in ANTU-treated rats.
Conclusions:
- Subcutaneous morphine exhibits a preventive effect against ANTU-induced pulmonary inflammation and edema.
- This protective action is mediated through peripheral opioid receptors.
- Endogenous opioids do not appear to play a significant role in modulating ANTU-induced lung damage.
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