Opioids in Cancer Pain Management: A Double-Edged Sword of Relief and Risk
Main Article Content
Keywords
Opioids, Cancer Pain, Immunosuppression, Infection Susceptibility, Tumour Progression, Ethical Prescribing, Multimodal Analgesia, Personalised Medicine
Abstract
Opioids are indispensable for managing cancer-related pain but carry risks such as immunosuppression, increased susceptibility to infections, and potential tumour progression. Balancing effective pain relief with these risks remains a critical challenge. This review examines the dual role of opioids in cancer pain management, highlighting their benefits, risks, and ethical implications while exploring strategies to mitigate adverse effects. Through a comprehensive literature review, we analysed mechanisms of opioid-induced immunosuppression, infection risks, tumour progression, and ethical prescribing practices. Additionally, strategies such as multimodal analgesia, opioid rotation, and personalised medicine were evaluated. Findings indicate that while opioids effectively alleviate cancer pain, they may suppress immune function, elevate infection risks, and potentially promote tumour progression. Mitigation strategies, including multimodal approaches, immunomodulatory interventions, and adherence to ethical principles (beneficence, non-maleficence, autonomy, and justice), are essential for safe opioid use. In conclusion, opioids remain vital for cancer pain management but require judicious application to minimise risks. Future research should prioritise non-opioid alternatives and immunomodulatory therapies to enhance patient outcomes.
References
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2. Anekar AA, Hendrix JM, Cascella M. WHO Analgesic Ladder. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 Feb 17]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK554435/
3. Paice JA, Bohlke K, Barton D, Craig DS, El-Jawahri A, Hershman DL, et al. Use of Opioids for Adults with Pain From Cancer or Cancer Treatment: ASCO Guideline. J Clin Oncol Off J Am Soc Clin Oncol. 2023 Feb 1;41(4):914–30.
4. Hemmings HC, Lambert DG. The good, the bad, and the ugly: the many faces of opioids. Br J Anaesth. 2019 Jun;122(6):705–7.
5. Bruera E, Paice JA. Cancer pain management: safe and effective use of opioids. Am Soc Clin Oncol Educ Book Am Soc Clin Oncol Annu Meet. 2015;e593-599.
6. Bovill JG. Mechanisms of actions of opioids and non-steroidal anti-inflammatory drugs. Eur J Anaesthesiol Suppl. 1997 May; 15:9–15.
7. Ballantyne JC. Chronic pain following treatment for cancer: the role of opioids. The Oncologist. 2003;8(6):567–75.
8. Tuan J, Wang EH, De Leon JRC, Mendoza MJ, Varrassi G. Management of Acute Cancer Pain in Asia: An Expert Opinion on the Role of Tramadol/Dexketoprofen Fixed-Dose Combination. Cureus. 15(3):e35770.
9. Scarborough BM, Smith CB. Optimal pain management for patients with cancer in the modern era. CA Cancer J Clin. 2018 May;68(3):182–96.
10. Fallon M, Giusti R, Aielli F, Hoskin P, Rolke R, Sharma M, et al. Management of cancer pain in adult patients: ESMO Clinical Practice Guidelines. Ann Oncol Off J Eur Soc Med Oncol. 2018 Oct 1;29(Suppl 4):iv166–91.
11. Subedi M, Bajaj S, Kumar MS, Yc M. An overview of tramadol and its usage in pain management and future perspective. Biomed Pharmacother Biomedecine Pharmacother. 2019 Mar;111:443–51.
12. Pysz-Waberski D, Sadurska J, Kędzierska-Jamróz J, Pietrzyński Ł, Lorek A, Jarosz M, et al. Multidisciplinary management of chronic pain in elderly oncology patients. Contemp Oncol Onkol. 2022;26(3):157–64.
13. Wong SSC, Cheung CW. Optimization of opioid utility in cancer pain populations. Ann Palliat Med. 2020 Mar;9(2):558–70.
14. Parthasarathy S, Singh A. Management of chronic malignant pain – an updated review. SBV J Basic Clin Appl Health Sci. 2019 Mar 1;2:3–7.
15. Karunarathna I. Morphine Sulfate: Clinical Applications and Pharmacological Considerations. 2024 May 2;
16. Vitzthum LK, Riviere P, Sheridan P, Nalawade V, Deka R, Furnish T, et al. Predicting Persistent Opioid Use, Abuse, and Toxicity Among Cancer Survivors. J Natl Cancer Inst. 2020 Jul 1;112(7):720–7.
17. Meske DS, Lawal OD, Elder H, Langberg V, Paillard F, Katz N. Efficacy of opioids versus placebo in chronic pain: a systematic review and meta-analysis of enriched enrollment randomized withdrawal trials. J Pain Res. 2018; 11:923–34.
18. Plein LM, Rittner HL. Opioids and the immune system - friend or foe. Br J Pharmacol. 2018 Jul;175(14):2717–25.
19. Rittner HL, Brack A, Stein C. Pain and the immune system. Br J Anaesth. 2008 Jul;101(1):40–4.
20. Bettinger JJ, Friedman BC. Opioids and Immunosuppression: Clinical Evidence, Mechanisms of Action, and Potential Therapies. Palliat Med Rep. 2024;5(1):70–80.
21. Roy S, Ninkovic J, Banerjee S, Charboneau RG, Das S, Dutta R, et al. Opioid drug abuse and modulation of immune function: consequences in susceptibility to opportunistic infections. J Neuroimmune Pharmacol Off J Soc NeuroImmune Pharmacol. 2011 Dec;6(4):442–65.
22. Kosciuczuk U, Knapp P, Lotowska-Cwiklewska AM. Opioid-induced immunosuppression, and carcinogenesis promotion theories create the newest trend in acute and chronic pain pharmacotherapy. Clinics. 2020;75:e1554.
23. Long X, Li Y, Qiu S, Liu J, He L, Peng Y. MiR-582-5p/miR-590-5p targeted CREB1/CREB5–NF-κB signaling and caused opioid-induced immunosuppression in human monocytes. Transl Psychiatry. 2016 Mar;6(3):e757.
24. Eisenstein TK. The Role of Opioid Receptors in Immune System Function. Front Immunol. 2019; 10:2904.
25. Hilburger ME, Adler MW, Truant AL, Meissler JJ, Satishchandran V, Rogers TJ, et al. Morphine induces sepsis in mice. J Infect Dis. 1997 Jul;176(1):183–8.
26. Meng J, Yu H, Ma J, Wang J, Banerjee S, Charboneau R, et al. Morphine induces bacterial translocation in mice by compromising intestinal barrier function in a TLR-dependent manner. PloS One. 2013;8(1):e54040.
27. Roy S, Charboneau RG, Barke RA. Morphine synergizes with lipopolysaccharide in a chronic endotoxemia model. J Neuroimmunol. 1999 Mar 1;95(1–2):107–14.
28. Tubaro E, Borelli G, Croce C, Cavallo G, Santiangeli C. Effect of morphine on resistance to infection. J Infect Dis. 1983 Oct;148(4):656–66.
29. El-Hage N, Gurwell JA, Singh IN, Knapp PE, Nath A, Hauser KF. Synergistic increases in intracellular Ca2+, and the release of MCP-1, RANTES, and IL-6 by astrocytes treated with opiates and HIV-1 Tat. Glia. 2005 Apr 15;50(2):91–106.
30. El-Hage N, Wu G, Wang J, Ambati J, Knapp PE, Reed JL, et al. HIV Tat1-72 and Opiate-induced changes in astrocytes promote chemotaxis of microglia through the expression of MCP-1 and alternative chemokines. Glia. 2006 Jan 15;53(2):132–46.
31. MacFarlane AS, Peng X, Meissler JJ, Rogers TJ, Geller EB, Adler MW, et al. Morphine increases susceptibility to oral Salmonella typhimurium infection. J Infect Dis. 2000 Apr;181(4):1350–8.
32. Wang J, Barke RA, Charboneau R, Roy S. Morphine impairs host innate immune response and increases susceptibility to Streptococcus pneumoniae lung infection. J Immunol Baltim Md 1950. 2005 Jan 1;174(1):426–34.
33. Ma J, Wang J, Wan J, Charboneau R, Chang Y, Barke RA, et al. Morphine disrupts interleukin-23 (IL-23)/IL-17-mediated pulmonary mucosal host defense against Streptococcus pneumoniae infection. Infect Immun. 2010 Feb;78(2):830–7.
34. Breslow JM, Monroy MA, Daly JM, Meissler JJ, Gaughan J, Adler MW, et al. Morphine, but not Trauma, Sensitizes to Systemic Acinetobacter baumannii Infection. J Neuroimmune Pharmacol Off J Soc NeuroImmune Pharmacol. 2011 Dec;6(4):551–65.
35. Peterson PK, Sharp B, Gekker G, Brummitt C, Keane WF. Opioid-mediated suppression of interferon-gamma production by cultured peripheral blood mononuclear cells. J Clin Invest. 1987 Sep;80(3):824–31.
36. Singh PP, Singal P. Morphine-induced Neuroimmunomodulation in Murine Visceral Leishmaniasis: The Role(s) of Cytokines and Nitric Oxide. J Neuroimmune Pharmacol. 2007 Dec 1;2(4):338–51.
37. Singh PP, Singh S, Dutta GP, Srimal RC. Immunomodulation by morphine in Plasmodium berghei-infected mice. Life Sci. 1994;54(5):331–9.
38. Fodale V, D’Arrigo MG, Triolo S, Mondello S, La Torre D. Anesthetic techniques and cancer recurrence after surgery. Scientific World Journal. 2014; 2014:328513.
39. Bajwa SJS, Anand S, Kaur G. Anesthesia and cancer recurrences: The current knowledge and evidence. J Cancer Res Ther. 2015;11(3):528–34.
40. Grandhi RK, Lee S, Abd-Elsayed A. Does Opioid Use Cause Angiogenesis and Metastasis? Pain Med Malden Mass. 2017 Jan 1;18(1):140–51.
41. Boland JW, Pockley AG. Influence of opioids on immune function in patients with cancer pain: from bench to bedside. Br J Pharmacol. 2018 Jul;175(14):2726–36.
42. Boland JW, McWilliams K, Ahmedzai SH, Pockley AG. Effects of opioids on immunologic parameters that are relevant to anti-tumour immune potential in patients with cancer: a systematic literature review. Br J Cancer. 2014 Aug 26;111(5):866–73.
43. Wiese AD, Griffin MR, Schaffner W, Stein CM, Greevy RA, Mitchel EF, et al. Long-acting Opioid Use and the Risk of Serious Infections: A Retrospective Cohort Study. Clin Infect Dis Off Publ Infect Dis Soc Am. 2019 May 17;68(11):1862–9.
44. Ripamonti CI, Chelazzi C. Total pain, opioids, and immune checkpoint inhibitors in the survival of patients with cancer. ESMO Open. 2024 Sep;9(9):103688.
45. Li Y, Sun L, Zhou Q, Lee AJ, Wang L, Zhang R, et al. Effects of opioid drugs on immune function in cancer patients. Biomed Pharmacother Biomedecine Pharmacother. 2024 Jun;175:116665.
46. Beloeil H, Albaladejo P, Sion A, Durand M, Martinez V, Lasocki S, et al. Multicentre, prospective, double-blind, randomised controlled clinical trial comparing different non-opioid analgesic combinations with morphine for postoperative analgesia: the OCTOPUS study. Br J Anaesth. 2019 Jun;122(6):e98–106.
47. Shi Y, Wu W. Multimodal non-invasive non-pharmacological therapies for chronic pain: mechanisms and progress. BMC Med. 2023 Sep 29;21(1):372.
48. Kotalik J. Controlling pain and reducing misuse of opioids. Can Fam Physician. 2012 Apr;58(4):381–5.
49. Fine RL. Ethical and practical issues with opioids in life-limiting illness. Proc Bayl Univ Med Cent. 2007 Jan;20(1):5–12.
50. Mercadante S, Bruera E. Methadone as a First-Line Opioid in Cancer Pain Management: A Systematic Review. J Pain Symptom Manage. 2018 Mar;55(3):998–1003.
51. Raphael J, Ahmedzai S, Hester J, Urch C, Barrie J, Williams J, et al. Cancer pain: part 1: Pathophysiology; oncological, pharmacological, and psychological treatments: a perspective from the British Pain Society endorsed by the UK Association of Palliative Medicine and the Royal College of General Practitioners. Pain Med Malden Mass. 2010 May;11(5):742–64.
52. Raad M, López WOC, Sharafshah A, Assefi M, Lewandrowski KU. Personalized Medicine in Cancer Pain Management. J Pers Med. 2023 Jul 28;13(8):1201.
53. Dey S, Sanders AE, Martinez S, Kopitnik NL, Vrooman BM. Alternatives to Opioids for Managing Pain. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 Feb 18]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK574543/
54. Estapé J, Viñolas N, González B, Inglés F, Bofill T, Guzmán MC, et al. Ketorolac, a new non-opioid analgesic: a double-blind trial versus pentazocine in cancer pain. J Int Med Res. 1990;18(4):298–304.
55. Brown DC, Agnello K. Intrathecal substance P-saporin in the dog: efficacy in bone cancer pain. Anesthesiology. 2013 Nov;119(5):1178–85.
56. Mustafa G, Anderson EM, Bokrand-Donatelli Y, Neubert JK, Caudle RM. Anti-nociceptive effect of a conjugate of substance P and light chain of botulinum neurotoxin type A. Pain. 2013 Nov;154(11):2547–53.
57. Brown DC, Iadarola MJ, Perkowski SZ, Erin H, Shofer F, Laszlo KJ, et al. Physiologic and antinociceptive effects of intrathecal resiniferatoxin in a canine bone cancer model. Anesthesiology. 2005 Nov;103(5):1052–9.
58. Bevan S, Quallo T, Andersson DA. TRPV1. Handb Exp Pharmacol. 2014; 222:207–45.
59. Kissin I, Szallasi A. Therapeutic Targeting of TRPV1 by Resiniferatoxin, from Preclinical Studies to Clinical Trials. http://www.eurekaselect.com [Internet]. [cited 2025 Feb 20]; Available from: https://www.eurekaselect.com/article/33645
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Sep 19, 2025
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Omokore, olutomiwa, Quadri, I., Kingdom, P., Ogbuiyi-chima, I., Meribole, S., Olayinka, T., Ogunnoiki, S., Precious, S.-O., Olaitan, A., Chima-Ogbuiyi, N., Ifeanyichukwu, O., Ikpegbu, R., Adelakun, F., Aderinboye, P., okpanachi, P., Oladeji, O., Baah, H., Edochie, P., & Tsegah, D. (2025). Opioids in Cancer Pain Management: A Double-Edged Sword of Relief and Risk. Nigerian Medical Journal, 66(3), 849–866. https://doi.org/10.71480/nmj.v66i3.592
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