PDF
ePub
Citation
Print
Abstract
Controlling pain in cancer patients is important for several reasons including patient quality of life (QOL). In moderate-to-severe cancer-pain management, opioid analgesics are indispensable. Among these, morphine is the most representative. Unfortunately, many studies have shown that morphine is potentially associated with cancer growth, recurrence, and metastasis. Specifically, in animal as well as in vivo and in vitro studies, morphine has been demonstrated to have possibly positive effects on cancer progression. However, those effects have not yet been confirmed as entirely harmful, for several reasons: the results of animal and laboratory research have not been subjected to clinical trials; there are as yet no well-designed clinical studies, and indeed, some studies have shown that morphine can have negative, suppression effects on tumor growth. This review paper will present some of the data on the potentially positive relationships between morphine and cancer. It should not be forgotten, though, that such relationships remain controversial, and that pain itself promotes cancer progression.
REFERENCES
1.van den Beuken-van Everdingen MH., de Rijke JM., Kessels AG., Schouten HC., van Kleef M., Patijn J. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol. 2007. 18:1437–49.
2.Haumann J., Joosten EB., Everdingen MH. Pain prevalence in cancer patients: status quo or opportunities for improvement? Curr Opin Support Palliat Care. 2017.
3.Candido KD., Kusper TM., Knezevic NN. New Cancer Pain Treatment Options. Curr Pain Headache Rep. 2017. 21:12.
4.Vargas-Schaffer G. Is the WHO analgesic ladder still valid? Twenty-four years of experience. Can Fam Physician. 2010. 56:514–7.
5.Ma Y., Ren Z., Ma S., Yan W., He M., Wang D, et al. Morphine enhances renal cell carcinoma aggressiveness through promotes survivin level. Ren Fail. 2017. 39:258–64.
6.Bimonte S., Barbieri A., Rea D., Palma G., Luciano A., Cuomo A, et al. Morphine Promotes Tumor Angiogenesis and Increases Breast Cancer Progression. Biomed Res Int. 2015. 2015:161508.
7.Nguyen J., Luk K., Vang D., Soto W., Vincent L., Robiner S, et al. Morphine stimulates cancer progression and mast cell activation and impairs survival in transgenic mice with breast cancer. Br J Anaesth. 2014. 113(Suppl 1):i4–13.
8.Vassou D., Notas G., Hatzoglou A., Castanas E., Kampa M. Opioids increase bladder cancer cell migration via bradykinin B2 receptors. Int J Oncol. 2011. 39:697–707.
9.Farooqui M., Li Y., Rogers T., Poonawala T., Griffin RJ., Song CW, et al. COX-2 inhibitor celecoxib prevents chronic morphine-induced promotion of angiogenesis, tumour growth, metastasis and mortality, without compromising analgesia. Br J Cancer. 2007. 97:1523–31.
10.Sasamura T., Nakamura S., Iida Y., Fujii H., Murata J., Saiki I, et al. Morphine analgesia suppresses tumor growth and metastasis in a mouse model of cancer pain produced by orthotopic tumor inoculation. Eur J Pharmacol. 2002. 441:185–91.
11.Koodie L., Yuan H., Pumper JA., Yu H., Charboneau R., Ramkrishnan S, et al. Morphine inhibits migration of tumor-infiltrating leukocytes and suppresses angiogenesis associated with tumor growth in mice. Am J Pathol. 2014. 184:1073–84.
12.Afsharimani B., Baran J., Watanabe S., Lindner D., Cabot PJ., Parat MO. Morphine and breast tumor metastasis: the role of matrix-degrading enzymes. Clin Exp Metastasis. 2014. 31:149–58.
13.Li G., Low PS. Synthesis and evaluation of a ligand targeting the μ and δ opioid receptors for drug delivery to lung cancer. Bioorg Med Chem Lett. 2017. 27:2074–8.
14.Lennon FE., Moss J., Singleton PA. The μ-opioid receptor in cancer progression: is there a direct effect? Anesthesiology. 2012. 116:940–5.
15.Grandhi RK., Lee S., Abd-Elsayed A. Does Opioid Use Cause Angiogenesis and Metastasis? Pain Med. 2017. 18:140–51.
16.Roy S., Ninkovic J., Banerjee S., Charboneau RG., Das S., Dutta R, et al. Opioid drug abuse and modu- lation of immune function: consequences in the susceptibility to opportunistic infections. J Neuroimmune Pharmacol. 2011. 6:442–65.
17.Roy S., Wang J., Kelschenbach J., Koodie L., Martin J. Modulation of immune function by morphine: implications for susceptibility to infection. J Neuroimmune Pharmacol. 2006. 1:77–89.
18.Grivennikov SI., Greten FR., Karin M. Immunity, inflammation, and cancer. Cell. 2010. 140:883–99.
19.Finley MJ., Happel CM., Kaminsky DE., Rogers TJ. Opioid and nociceptin receptors regulate cyto-kine and cytokine receptor expression. Cell Immunol. 2008. 252:146–54.
20.Lennon FE., Mirzapoiazova T., Mambetsariev B., Salgia R., Moss J., Singleton PA. Overexpression of the μ-opioid receptor in human non-small cell lung cancer promotes Akt and mTOR activation, tumor growth, and metastasis. Anesthesiology. 2012. 116:857–67.
21.Gach K., Wyrębska A., Fichna J., Janecka A. The role of morphine in regulation of cancer cell growth. Naunyn Schmiedebergs Arch Pharmacol. 2011. 384:221–30.
22.Bortsov AV., Millikan RC., Belfer I., Boortz-Marx RL., Arora H., McLean SA. μ-Opioid receptor gene A118G polymorphism predicts survival in patients with breast cancer. Anesthesiology. 2012. 116:896–902.
23.Dunn GP., Old LJ., Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004. 21:137–48.
24.Carr DJ., Rogers TJ., Weber RJ. The relevance of opioids and opioid receptors on immunocompetence and immune homeostasis. Proc Soc Exp Biol Med. 1996. 213:248–57.
25.Wigmore T., Farquhar-Smith P. Opioids and cancer: friend or foe? Curr Opin Support Palliat Care. 2016. 10:109–18.
26.Gong L., Dong C., Ouyang W., Qin Q. Regulatory T cells: a possible promising approach to cancer recurrence induced by morphine. Med Hypotheses. 2013. 80:308–10.
27.Hua S., Cabot PJ. Mechanisms of peripheral immune-cell-mediated analgesia in inflammation: clinical and therapeutic implications. Trends Pharmacol Sci. 2010. 31:427–33.
28.Yin D., Mufson RA., Wang R., Shi Y. Fas-mediated cell death promoted by opioids. Nature. 1999. 397:218.
29.Hayashi T., Tsao LI., Su TP. Antiapoptotic and cytotoxic properties of delta opioid peptide [D-Ala(2),D-Leu(5)]enkephalin in PC12 cells. Synapse. 2002. 43:86–94.
30.Afsharimani B., Cabot P., Parat MO. Morphine and tumor growth and metastasis. Cancer Metastasis Rev. 2011. 30:225–38.
31.Hatsukari I., Hitosugi N., Ohno R., Hashimoto K., Nakamura S., Satoh K, et al. Induction of apoptosis by morphine in human tumor cell lines in vitro. Anticancer Res. 2007. 27:857–64.
32.Singleton PA., Mambetsariev N., Lennon FE., Mathew B., Siegler JH., Moreno-Vinasco L, et al. Methylnaltrexone potentiates the anti-angiogenic effects of mTOR inhibitors. J Angiogenes Res. 2010. 2:5.
XML Download