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Updated: Aug 12, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Immunosuppression by morphine-induced lymphocyte apoptosis: is it a real issue?
Takeshi Ohara1, Tsunetoshi Itoh, Masahiko Takahashi
1*Division of Pain Control, Department of Anesthesiology and Emergency Medicine, and †Division of Immunology and Embryology, Department of Cell Biology, Tohoku University Graduate School of Medicine, and ‡Division of Dento-oral Anesthesiology, Department of Oral Medicine and Surgery, Tohoku University Graduate School of Dentistry, Sendai, Japan.
Morphine does not appear to induce apoptosis in human lymphocytes, contrary to recent concerns. This study found no evidence of morphine-induced cell death, suggesting current opioid use for cancer pain management is likely safe.
Area of Science:
- Immunology
- Pharmacology
Background:
- Recent studies suggest morphine may induce apoptosis in human peripheral blood lymphocytes (PBLs).
- This raises concerns regarding the safety of opioid-based pain management strategies, particularly in cancer patients.
Purpose of the Study:
- To investigate whether morphine induces apoptosis in cultured human PBLs.
- To evaluate the impact of morphine on key apoptosis markers and pathways.
Main Methods:
- Human PBLs were cultured with etoposide (positive control), morphine, or vehicle.
- Apoptosis was assessed via flow cytometry, detecting phosphatidylserine, nuclear fragmentation, Fas, Bcl-2, and Caspase-3 activity.
- Co-incubation with a Fas-specific antibody was also performed.
Main Results:
- Etoposide significantly induced apoptosis in PBLs.
- Morphine treatment did not alter the expression of apoptosis-related molecules or induce significant apoptotic processes.
- Fas-specific antibody co-incubation did not enhance apoptosis in morphine-treated cultures.
Conclusions:
- The findings do not support the hypothesis that morphine directly causes PBL apoptosis and subsequent immunosuppression.
- Morphine's use for optimal pain relief in cancer patients should not be discouraged based on current evidence.
- Further research is needed to fully clarify the relationship between morphine and lymphocyte apoptosis.
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