{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:05:29Z","timestamp":1790701529401,"version":"4.1.0"},"reference-count":163,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Managing cancer-related pain presents complex challenges involving the interplay between analgesic efficacy, immune system responses, and patient outcomes. Methods: Following the Scale for the Assessment of Narrative Review Articles (SANRA) criteria, we conducted a comprehensive literature search in Medline, Scopus, and Web of Science databases. The review synthesized evidence regarding opioid pain management modalities, genetic variations affecting pain perception, and associated drug metabolism. Results: The literature reveals significant associations between opioid administration and immune function, with potential implications for cancer progression and survival. Genetic polymorphisms in key genes influence individual responses to pain opioid metabolism and, finally, pain management strategies. The immunosuppressive effects of opioids emerge as a critical consideration in cancer pain management, potentially influencing disease progression and treatment outcomes. Conclusions: Genetic variants influence analgesic efficacy, while the interaction between opioid-induced immunosuppression and genetic factors impacts both pain control and survival outcomes. This emphasizes the need for personalized treatment approaches considering individual genetic profiles and immune function.<\/jats:p>","DOI":"10.3390\/cancers17050863","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T04:58:17Z","timestamp":1741064297000},"page":"863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effects of Opioids in Cancer Pain: An Interplay Among Genetic Factors, Immune Response, and Clinical Outcomes\u2014A Scoping Review"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3714-0117","authenticated-orcid":false,"given":"Kamil","family":"Adamczyk","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, National Medical Institute of the Ministry of the Interior and Administration, 02-507 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7312-1880","authenticated-orcid":false,"given":"Konrad","family":"Zuzda","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, National Medical Institute of the Ministry of the Interior and Administration, 02-507 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2828-571X","authenticated-orcid":false,"given":"Mi\u0142osz","family":"Jankowski","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, National Medical Institute of the Ministry of the Interior and Administration, 02-507 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafa\u0142","family":"\u015awierczy\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, National Medical Institute of the Ministry of the Interior and Administration, 02-507 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0107-8515","authenticated-orcid":false,"given":"Kamil","family":"Chudzi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, National Medical Institute of the Ministry of the Interior and Administration, 02-507 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartosz","family":"Czapski","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, National Medical Institute of the Ministry of the Interior and Administration, 02-507 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2501-4727","authenticated-orcid":false,"given":"Konstanty","family":"Szu\u0142drzy\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, National Medical Institute of the Ministry of the Interior and Administration, 02-507 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"i109","DOI":"10.1093\/bja\/aeu351","article-title":"Association of Opioid Requirement and Cancer Pain with Survival in Advanced Non-Small Cell Lung Cancer","volume":"113","author":"Zylla","year":"2014","journal-title":"Br. J. Anaesth."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e19306","DOI":"10.1097\/MD.0000000000019306","article-title":"The Impact of Pain and Opioids Use on Survival in Cancer Patients","volume":"99","author":"Zheng","year":"2020","journal-title":"Medicine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1200\/JCO.2010.28.4455","article-title":"Decrease in Depression Symptoms Is Associated with Longer Survival in Patients with Metastatic Breast Cancer: A Secondary Analysis","volume":"29","author":"Collie","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5349","DOI":"10.1002\/cncr.24561","article-title":"Depression as a Predictor of Disease Progression and Mortality in Cancer Patients","volume":"115","author":"Satin","year":"2009","journal-title":"Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1111\/anae.14813","article-title":"Pharmacogenetics of Opioids: A Narrative Review","volume":"74","author":"Kumar","year":"2019","journal-title":"Anaesthesia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1097\/ALN.0000000000004677","article-title":"Association of Genetic Variants with Postsurgical Pain: A Systematic Review and Meta-Analyses","volume":"139","author":"Frangakis","year":"2023","journal-title":"Anesthesiology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s41073-019-0064-8","article-title":"SANRA\u2014A Scale for the Quality Assessment of Narrative Review Articles","volume":"4","author":"Baethge","year":"2019","journal-title":"Res. Integr. Peer Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1007\/s00520-017-3614-y","article-title":"A Systematic Review of the Impact of Pain on Overall Survival in Patients with Cancer","volume":"25","author":"Zylla","year":"2017","journal-title":"Support. Care Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/j.jpain.2014.07.003","article-title":"Survival Patterns in Squamous Cell Carcinoma of the Head and Neck: Pain as an Independent Prognostic Factor for Survival","volume":"15","author":"Anderson","year":"2014","journal-title":"J. Pain"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1136\/bmjspcare-2020-002624","article-title":"State of the Science: Opioids and Survival in Cancer Pain Management","volume":"10","author":"Boland","year":"2020","journal-title":"BMJ Support. Palliat. Care"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.6004\/jnccn.2014.0122","article-title":"Improving Cancer Pain Control with NCCN Guideline-Based Analgesic Administration: A Patient-Centered Outcome","volume":"12","author":"Janjan","year":"2014","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/s00520-024-08681-2","article-title":"Impact of Opioid Analgesics on Survival in Cancer Patients Receiving Immune Checkpoint Inhibitors","volume":"32","author":"Kavgaci","year":"2024","journal-title":"Support. Care Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1016\/j.athoracsur.2020.09.015","article-title":"Prolonged Opioid Use Associated with Reduced Survival After Lung Cancer Resection","volume":"111","author":"Chancellor","year":"2021","journal-title":"Ann. Thorac. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1007\/s00432-022-04513-0","article-title":"The Negative Impact of Opioids on Cancer Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis","volume":"149","author":"Ju","year":"2022","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e659","DOI":"10.1200\/OP.21.00488","article-title":"Opioid Prescription Is Associated with Increased Survival in Older Adult Patients with Pancreatic Cancer in the United States: A Propensity Score Analysis","volume":"18","author":"Zylberberg","year":"2022","journal-title":"JCO Oncol Pract."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1007\/s11864-023-01091-2","article-title":"Effects of Opioids on Immune and Endocrine Function in Patients with Cancer Pain","volume":"24","author":"Bradley","year":"2023","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1097\/AJP.0000000000000405","article-title":"Contribution of Opiate Analgesics to the Development of Infections in Advanced Cancer Patients","volume":"33","author":"Shao","year":"2017","journal-title":"Clin. J. Pain"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.bja.2020.10.021","article-title":"Intraoperative Opioids Are Associated with Improved Recurrence-Free Survival in Triple-Negative Breast Cancer","volume":"126","author":"Montagna","year":"2021","journal-title":"Br. J. Anaesth."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.bja.2021.03.030","article-title":"Intraoperative Opioid Exposure, Tumour Genomic Alterations, and Survival Differences in People with Lung Adenocarcinoma","volume":"127","author":"Connolly","year":"2021","journal-title":"Br. J. Anaesth."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1177\/1073858414525828","article-title":"The Neurobiology of Cancer Pain","volume":"20","author":"Schmidt","year":"2014","journal-title":"Neuroscientist"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8593","DOI":"10.1523\/JNEUROSCI.3993-14.2015","article-title":"Persistent Nociception Triggered by Nerve Growth Factor (NGF) Is Mediated by TRPV1 and Oxidative Mechanisms","volume":"35","author":"Eskander","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3102","DOI":"10.1016\/j.celrep.2017.11.066","article-title":"Functional and Molecular Characterization of Mechanoinsensitive \u201cSilent\u201d Nociceptors","volume":"21","author":"Prato","year":"2017","journal-title":"Cell Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Shillo, P., Yiangou, Y., Donatien, P., Greig, M., Selvarajah, D., Wilkinson, I.D., Anand, P., and Tesfaye, S. (2021). Nerve and Vascular Biomarkers in Skin Biopsies Differentiate Painful from Painless Peripheral Neuropathy in Type 2 Diabetes. Front. Pain Res., 2.","DOI":"10.3389\/fpain.2021.731658"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"15113","DOI":"10.1523\/JNEUROSCI.3947-10.2010","article-title":"IL-6- and NGF-Induced Rapid Control of Protein Synthesis and Nociceptive Plasticity via Convergent Signaling to the eIF4F Complex","volume":"30","author":"Melemedjian","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.1097\/j.pain.0000000000001986","article-title":"Peripheral Nerve Injury and Sensitization Underlie Pain Associated with Oral Cancer Perineural Invasion","volume":"161","author":"Salvo","year":"2020","journal-title":"Pain"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"659","DOI":"10.3109\/0284186X.2016.1167958","article-title":"Pain following cancer treatment: Guidelines for the clinical classification of predominant neuropathic, nociceptive and central sensitization pain","volume":"55","author":"Nijs","year":"2016","journal-title":"Acta Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/nrn.2016.162","article-title":"Structural plasticity and reorganisation in chronic pain","volume":"18","author":"Kuner","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.pain.2003.08.002","article-title":"Alterations in dorsal horn neurones in a rat model of cancer-induced bone pain","volume":"106","author":"Urch","year":"2003","journal-title":"Pain"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7950","DOI":"10.1523\/JNEUROSCI.5250-14.2015","article-title":"Delayed Activation of Spinal Microglia Contributes to the Maintenance of Bone Cancer Pain in Female Wistar Rats via P2X7 Receptor and IL-18","volume":"35","author":"Yang","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1007\/s40122-020-00183-3","article-title":"Successful Treatment of Refractory Cancer Pain and Depression with Continuous Intrathecal Administration of Dexmedetomidine and Morphine: A Case Report","volume":"9","author":"Huang","year":"2020","journal-title":"Pain Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2022-11-7","DOI":"10.7573\/dic.2022-11-7","article-title":"Multidisciplinary Approach, Continuous Care and Opioid Management in Cancer Pain: Case Series and Review of the Literature","volume":"12","author":"Porzio","year":"2023","journal-title":"Drugs Context"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1159\/000338579","article-title":"Cancer Pain Management and Bone Metastases: An Update for the Clinician","volume":"7","author":"Schneider","year":"2012","journal-title":"Breast Care"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.jfma.2011.03.005","article-title":"Efficacy of Intrathecal Drug Delivery System for Refractory Cancer Pain Patients: A Single Tertiary Medical Center Experience","volume":"111","author":"Lin","year":"2012","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1093\/brain\/awac153","article-title":"Chronic Pain Recruits Hypothalamic Dynorphin\/Kappa Opioid Receptor Signalling to Promote Wakefulness and Vigilance","volume":"146","author":"Ito","year":"2023","journal-title":"Brain"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5698640","DOI":"10.1155\/2017\/5698640","article-title":"Cancer Pain Management and Pain Interference with Daily Functioning among Cancer Patients in Gondar University Hospital","volume":"2017","author":"Tegegn","year":"2017","journal-title":"Pain Res. Manag."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"251","DOI":"10.18203\/2319-2003.ijbcp20170316","article-title":"Adequacy of Pain Management in Oncology Patients at a Tertiary Hospital in Ghana","volume":"6","author":"Abruquah","year":"2017","journal-title":"Int. J. Basic Clin. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jpainsymman.2010.03.025","article-title":"Change in Cancer Pain Management in Korea Between 2001 and 2006: Results of Two Nationwide Surveys","volume":"41","author":"Hong","year":"2011","journal-title":"J. Pain Symptom Manag."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1200\/JGO.2015.001859","article-title":"Cancer Pain Management Insights and Reality in Southeast Asia: Expert Perspectives from Six Countries","volume":"2","author":"Javier","year":"2016","journal-title":"J. Glob. Oncol."},{"key":"ref_39","first-page":"1423","article-title":"Pain Polymorphisms and Opioids: An Evidence Based Review","volume":"19","author":"Vieira","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e0849","DOI":"10.1097\/CCE.0000000000000849","article-title":"Assessment of Opioid-Induced Immunomodulation in Experimental and Clinical Sepsis","volume":"5","author":"Bissell","year":"2023","journal-title":"Crit. Care Explor."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1089\/pmr.2023.0049","article-title":"Opioids and Immunosuppression: Clinical Evidence, Mechanisms of Action, and Potential Therapies","volume":"5","author":"Bettinger","year":"2024","journal-title":"Palliat. Med. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1146\/annurev-med-062613-093100","article-title":"Opioid Receptors","volume":"67","author":"Stein","year":"2016","journal-title":"Annu. Rev. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1177\/2049463712438493","article-title":"Basic Opioid Pharmacology: An Update","volume":"6","author":"Pathan","year":"2012","journal-title":"Br. J. Pain"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s00726-011-1163-0","article-title":"Role of the Mu-Opioid Receptor in Opioid Modulation of Immune Function","volume":"45","author":"Roy","year":"2013","journal-title":"Amino Acids"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Stein, C. (2013). Targeting Pain and Inflammation by Peripherally Acting Opioids. Front. Pharmacol., 4.","DOI":"10.3389\/fphar.2013.00123"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1177\/1049909106289068","article-title":"The Adverse Effects of Morphine: A Prospective Survey of Common Symptoms during Repeated Dosing for Chronic Cancer Pain","volume":"23","author":"Glare","year":"2006","journal-title":"Am. J. Hosp. Palliat. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"S105","DOI":"10.36076\/ppj.2008\/11\/S105","article-title":"Opioid Complications and Side Effects","volume":"11","author":"Benyamin","year":"2008","journal-title":"Pain Physician"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1080\/17425255.2019.1634053","article-title":"Opioids and the Risk of Infection: A Critical Appraisal of the Pharmacologic and Clinical Evidence","volume":"15","author":"Kurteva","year":"2019","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2726","DOI":"10.1111\/bph.13903","article-title":"Influence of Opioids on Immune Function in Patients with Cancer Pain: From Bench to Bedside","volume":"175","author":"Boland","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Wen, S., Jiang, Y., Liang, S., Cheng, Z., Zhu, X., and Guo, Q. (2021). Opioids Regulate the Immune System: Focusing on Macrophages and Their Organelles. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.814241"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1007\/s11481-011-9292-5","article-title":"Opioid Drug Abuse and Modulation of Immune Function: Consequences in the Susceptibility to Opportunistic Infections","volume":"6","author":"Roy","year":"2011","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"McLaughlin, P.J., McHugh, D.P., Magister, M.J., and Zagon, I.S. (2015). Endogenous Opioid Inhibition of Proliferation of T and B Cell Subpopulations in Response to Immunization for Experimental Autoimmune Encephalomyelitis. BMC Immunol., 16.","DOI":"10.1186\/s12865-015-0093-0"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Skiba, D., Jasku\u0142a, K., Nawrocka, A., Pozna\u0144ski, P., \u0141azarczyk, M., Szyma\u0144ski, \u0141., \u017bera, T., Sacharczuk, M., Cudnoch-J\u0119drzejewska, A., and Gaciong, Z. (2024). The Role of Opioid Receptor Antagonists in Regulation of Blood Pressure and T-Cell Activation in Mice Selected for High Analgesia Induced by Swim Stress. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052618"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1097\/j.pain.0000000000000306","article-title":"Is Regular Systemic Opioid Analgesia Associated with Shorter Survival in Adult Patients with Cancer? A Systematic Literature Review","volume":"156","author":"Boland","year":"2015","journal-title":"Pain"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Chen, S., Liu, J., and Huang, S. (2024). Effect of Repeated Intraperitoneal Injections of Different Concentrations of Oxycodone on Immune Function in Mice. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1370663"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e009962","DOI":"10.1136\/jitc-2024-009962","article-title":"Morphine Treatment Restricts Response to Immunotherapy in Oral Squamous Cell Carcinoma","volume":"12","author":"McIlvried","year":"2024","journal-title":"J. ImmunoTherapy Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Mao, Z., Jia, X., Jiang, P., Wang, Q., Zhang, Y., Li, Y., Fu, X., Jiao, M., Jiang, L., and Liu, Z. (2022). Effect of Concomitant Use of Analgesics on Prognosis in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.861723"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1111\/bph.13750","article-title":"Opioids and the Immune System\u2014Friend or Foe","volume":"175","author":"Plein","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1097\/MS9.0000000000000462","article-title":"Herpes Simplex Encephalitis in a Patient Abusing Morphine: A Case Report from Nepal","volume":"85","author":"Kc","year":"2023","journal-title":"Ann. Med. Surg."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Puzhko, S., Eisenberg, M.J., Filion, K.B., Windle, S.B., H\u00e9bert-Losier, A., Gore, G., Paraskevopoulos, E., Martel, M.O., and Kudrina, I. (2022). Effectiveness of Interventions for Prevention of Common Infections Among Opioid Users: A Systematic Review of Systematic Reviews. Front. Public Health, 10.","DOI":"10.3389\/fpubh.2022.749033"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e2351933","DOI":"10.1001\/jamanetworkopen.2023.51933","article-title":"Prenatal Opioid Exposure and Immune-Related Conditions in Children","volume":"7","author":"Kelty","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e083791","DOI":"10.1136\/bmjopen-2023-083791","article-title":"Risk of Infections among Persons Treated with Opioids for Chronic Pain: A Systematic Review and Meta-Analysis Protocol","volume":"14","author":"Kudrina","year":"2024","journal-title":"BMJ Open"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Scarpa, J.R., Montagna, G., Plitas, G., Gulati, A., Fischer, G.W., and Mincer, J.S. (2023). Opioids and Immune Checkpoint Inhibitors Differentially Regulate a Common Immune Network in Triple-Negative Breast Cancer. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1267532"},{"key":"ref_64","first-page":"125","article-title":"Update on the Pharmacogenomics of Pain Management","volume":"12","author":"Kaye","year":"2019","journal-title":"Pharmacogenomics Pers. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/nature10939","article-title":"Structure of the Human \u03ba-Opioid Receptor in Complex with JDTic","volume":"485","author":"Wu","year":"2012","journal-title":"Nature"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2258","DOI":"10.1111\/bph.13047","article-title":"A 6 V Polymorphism of the Human \u03bc-opioid Receptor Decreases Signalling of Morphine and Endogenous Opioids in Vitro","volume":"172","author":"Knapman","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2478\/raon-2023-0003","article-title":"Association of OPRM1, MIR23B, and MIR107 Genetic Variability with Acute Pain, Chronic Pain and Adverse Effects after Postoperative Tramadol and Paracetamol Treatment in Breast Cancer","volume":"57","author":"Vidic","year":"2023","journal-title":"Radiol. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2941","DOI":"10.7150\/ijms.49297","article-title":"Mu-Opioid Receptor Polymorphisms and Breast Cancer Recurrence in Adult Korean Women Undergoing Breast Cancer Surgery: A Retrospective Study","volume":"17","author":"Lee","year":"2020","journal-title":"Int. J. Med. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/0885-3924(92)90059-Q","article-title":"A Long-Term Survey of Morphine in Cancer Pain Patients","volume":"7","author":"Schug","year":"1992","journal-title":"J Pain Symptom Manag."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jpainsymman.2014.05.015","article-title":"Patterns of Community-Based Opioid Prescriptions in People Dying of Cancer","volume":"49","author":"Gagnon","year":"2015","journal-title":"J. Pain Symptom Manag."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Preux, C., Bertin, M., Tarot, A., Authier, N., Pinol, N., Brugnon, D., Pereira, B., and Guastella, V. (2022). Prevalence of Opioid Use Disorder among Patients with Cancer-Related Pain: A Systematic Review. J. Clin. Med., 11.","DOI":"10.3390\/jcm11061594"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.jpain.2017.04.001","article-title":"OPRM1 Methylation Contributes to Opioid Tolerance in Cancer Patients","volume":"18","author":"Viet","year":"2017","journal-title":"J. Pain"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/bcpt.12757","article-title":"Genetic Influences of OPRM1,OPRD1 and COMT on Morphine Analgesia in a Multi-Modal, Multi-Tissue Human Experimental Pain Model","volume":"121","author":"Nielsen","year":"2017","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_74","first-page":"1408","article-title":"The Characteristics and the Pharmacological Management of Cancer Pain and Its Effect on the Patients\u2019 Daily Activities and Their Quality of Life: A Cross\u2014Sectional Study from Malaysia","volume":"7","author":"Kc","year":"2013","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Par\u00e1s-Bravo, P., Paz-Zulueta, M., Boixadera-Planas, E., Fradejas-Sastre, V., Palacios-Ce\u00f1a, D., Fern\u00e1ndez-de-las-Pe\u00f1as, C., and Alonso-Blanco, C. (2020). Cancer Patients and Anxiety: A Gender Perspective. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17041302"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1111\/papr.13053","article-title":"Measuring Pain in Oncology Outpatients: Numeric Rating Scale Versus Acceptable\/Non Acceptable Pain. A Prospective Single Center Study","volume":"21","author":"Kudrashou","year":"2021","journal-title":"Pain Pract."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Schalo, I., Durand, C.D., and Standifer, K.M. (2019). Sex Differences in Nociceptin\/Orphanin FQ Peptide Receptor-Mediated Pain and Anxiety Symptoms in a Preclinical Model of Post-Traumatic Stress Disorder. Front. Psychiatry, 9.","DOI":"10.3389\/fpsyt.2018.00731"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Daibani, A.E., and Che, T. (2022). Spotlight on Nociceptin\/Orphanin FQ Receptor in the Treatment of Pain. Molecules, 27.","DOI":"10.3390\/molecules27030595"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.bja.2018.06.024","article-title":"Nociceptin\/Orphanin FQ Receptor Ligands and Translational Challenges: Focus on Cebranopadol as an Innovative Analgesic","volume":"121","author":"Lambert","year":"2018","journal-title":"Br. J. Anaesth."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"107982","DOI":"10.1016\/j.pharmthera.2021.107982","article-title":"Therapeutic Potential of Nociceptin\/Orphanin FQ Peptide (NOP) Receptor Modulators for Treatment of Traumatic Brain Injury, Traumatic Stress, and Their Co-Morbidities","volume":"231","author":"Yacoub","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1124\/jpet.113.203984","article-title":"Effects of Spinally Administered Bifunctional Nociceptin\/Orphanin FQ Peptide Receptor\/\u03bc-Opioid Receptor Ligands in Mouse Models of Neuropathic and Inflammatory Pain","volume":"346","author":"Sukhtankar","year":"2013","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/bs.apha.2015.10.001","article-title":"Central N\/Ofq-Nop Receptor System in Pain Modulation","volume":"75","author":"Kiguchi","year":"2016","journal-title":"Adv. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1124\/jpet.111.184663","article-title":"Differential Effects of Nociceptin\/Orphanin FQ (NOP) Receptor Agonists in Acute Versus Chronic Pain: Studies with Bifunctional NOP\/\u03bc Receptor Agonists in the Sciatic Nerve Ligation Chronic Pain Model in Mice","volume":"339","author":"Khroyan","year":"2011","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1111\/bph.14899","article-title":"The Nociceptin\/Orphanin FQ Receptor System as a Target to Alleviate Cancer-induced Bone Pain in Rats: Model Validation and Pharmacological Evaluation","volume":"178","author":"Sliepen","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Popio\u0142ek-Barczyk, K., Rojewska, E., Jurga, A.M., Makuch, W., Zador, F., Borsodi, A., Piotrowska, A., Przew\u0142ocka, B., and Mika, J. (2014). Minocycline Enhances the Effectiveness of Nociceptin\/Orphanin FQ During Neuropathic Pain. Biomed Res. Int., 2014.","DOI":"10.1155\/2014\/762930"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1097\/j.pain.0000000000000597","article-title":"Nociceptin\/Orphanin FQ Receptor Expression in Clinical Pain Disorders and Functional Effects in Cultured Neurons","volume":"157","author":"Yiangou","year":"2016","journal-title":"Pain"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.pharmthera.2013.05.008","article-title":"Nociceptin\/Orphanin FQ Receptor Antagonists as Innovative Antidepressant Drugs","volume":"140","author":"Gavioli","year":"2013","journal-title":"Pharmacol. Ther."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.3892\/ol.2017.6457","article-title":"Voltage-Gated Calcium Channels: Novel Targets for Cancer Therapy","volume":"14","author":"Phan","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e54879","DOI":"10.7554\/eLife.54879","article-title":"Cell-Specific Exon Methylation and CTCF Binding in Neurons Regulate Calcium Ion Channel Splicing and Function","volume":"9","author":"Lipscombe","year":"2020","journal-title":"eLife"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s13041-019-0524-6","article-title":"Differential Regulation of Cav2.2 Channel Exon 37 Variants by Alternatively Spliced \u039c-Opioid Receptors","volume":"12","author":"Gandini","year":"2019","journal-title":"Mol. Brain"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Ribeiro, H., Sarmento-Ribeiro, A.B., Andrade, J.P., and Dourado, M. (2022). Apoptosis and (In) Pain\u2014Potential Clinical Implications. Biomedicines, 10.","DOI":"10.3390\/biomedicines10061255"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3211","DOI":"10.1002\/ptr.6768","article-title":"Investigating the Ameliorative Effect of Alpha-mangostin on Development and Existing Pain in a Rat Model of Neuropathic Pain","volume":"34","author":"Razavi","year":"2020","journal-title":"Phytother. Res."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Zhang, H., Li, N., Li, Z., Li, Y., Yu, Y., and Zhang, L. (2022). The Involvement of Caspases in Neuroinflammation and Neuronal Apoptosis in Chronic Pain and Potential Therapeutic Targets. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.898574"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Liao, M., Lu, K.-T., Hsu, J.-C., Lee, C.-H., Cheng, M., and Ro, L. (2022). The Role of Autophagy and Apoptosis in Neuropathic Pain Formation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052685"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"7132","DOI":"10.3892\/mmr.2015.4274","article-title":"Mangiferin Attenuates Contusive Spinal Cord Injury in Rats Through the Regulation of Oxidative Stress, Inflammation and the BCL-2 and Bax Pathway","volume":"12","author":"Luo","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Mokhtari, T., Yue, L., and Hu, L. (2023). Exogenous Melatonin Alleviates Neuropathic Pain-Induced Affective Disorders by Suppressing NF-\u03baB\/ NLRP3 Pathway and Apoptosis. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-28418-1"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1055\/s-0034-1383062","article-title":"Effects of Intraperitoneal Thymoquinone on Chronic Neuropathic Pain in Rats","volume":"80","author":"Amin","year":"2014","journal-title":"Planta Medica"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Kharrazi, A.E. (2024). Positive Correlation Between Bax and BCL-2 Gene Polymorphisms with the Risk of Endometriosis: A Case-Control Study. Int. J. Reprod. Biomed., 22.","DOI":"10.18502\/ijrm.v22i6.16796"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1489841","DOI":"10.1155\/2022\/1489841","article-title":"Electroacupuncture Alleviates Neuropathic Pain Through Regulating miR-206-3p Targeting BDNF After CCI","volume":"2022","author":"Tu","year":"2022","journal-title":"Neural Plast."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"137411","DOI":"10.1016\/j.neulet.2023.137411","article-title":"Electroacupuncture Attenuates Chronic Inflammatory Pain and Depression Comorbidity by Inhibiting Hippocampal Neuronal Apoptosis via the PI3K\/Akt Signaling Pathway","volume":"812","author":"Yang","year":"2023","journal-title":"Neurosci. Lett."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/tpj.2014.79","article-title":"Novel Associations between FAAH Genetic Variants and Postoperative Central Opioid-Related Adverse Effects","volume":"15","author":"Sadhasivam","year":"2015","journal-title":"Pharmacogenomics J."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2853","DOI":"10.1016\/j.pain.2013.08.026","article-title":"Associations between KCNJ6 (GIRK2) Gene Polymorphisms and Pain-Related Phenotypes","volume":"154","author":"Bruehl","year":"2013","journal-title":"Pain"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1097\/j.pain.0000000000000398","article-title":"Effect of Endocannabinoid Degradation on Pain","volume":"157","author":"Cajanus","year":"2016","journal-title":"Pain"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3851","DOI":"10.1093\/brain\/awad098","article-title":"Molecular Basis of FAAH-Out-Associated Human Pain Insensitivity","volume":"146","author":"Mikaeili","year":"2023","journal-title":"Brain"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.neuropharm.2014.11.024","article-title":"Attenuation of Persistent Pain-Related Behavior by Fatty Acid Amide Hydrolase (FAAH) Inhibitors in a Rat Model of HIV Sensory Neuropathy","volume":"95","author":"Nasirinezhad","year":"2015","journal-title":"Neuropharmacology"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Ozberk, D., Haywood, A., Sutherland, H.G., Yu, C., Albury, C.L., Zunk, M., George, R., Good, P., Griffiths, L.R., and Hardy, J. (2022). Association of KCNJ6 Rs2070995 and Methadone Response for Pain Management in Advanced Cancer at End-of-Life. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-21180-w"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1097\/FTD.0000000000000301","article-title":"Genetic Predisposition to Poor Opioid Response in Preterm Infants: Impact of KCNJ6 and COMT Polymorphisms on Pain Relief After Endotracheal Intubation","volume":"38","author":"Elens","year":"2016","journal-title":"Ther. Drug Monit."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"122","DOI":"10.3109\/01677063.2013.856430","article-title":"Variations in Potassium Channel Genes Are Associated with Breast Pain in Women Prior to Breast Cancer Surgery","volume":"28","author":"Langford","year":"2014","journal-title":"J. Neurogenet."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Smith, P.A. (2020). K+ Channels in Primary Afferents and Their Role in Nerve Injury-Induced Pain. Front. Cell. Neurosci., 14.","DOI":"10.3389\/fncel.2020.566418"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"107808","DOI":"10.1016\/j.pharmthera.2021.107808","article-title":"Therapeutic Potential of Targeting G Protein-Gated Inwardly Rectifying Potassium (GIRK) Channels in the Central Nervous System","volume":"223","author":"Jeremic","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/bph.15690","article-title":"Analgesic A-conotoxins Modulate Native and Recombinant GIRK1\/2 Channels via Activation of GABAB Receptors and Reduce Neuroexcitability","volume":"179","author":"Bony","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1002\/phar.1986","article-title":"Review of Opioid Pharmacogenetics and Considerations for Pain Management","volume":"37","author":"Obeng","year":"2017","journal-title":"Pharmacother. J. Hum. Pharmacol. Drug Ther."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/S0090-9556(25)07486-0","article-title":"Metabolism of Fentanyl, a Synthetic Opioid Analgesic, by Human Liver Microsomes. Role of CYP3A4","volume":"24","author":"Feierman","year":"1996","journal-title":"Drug Metab. Dispos."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.clpt.2004.05.003","article-title":"Role of Hepatic and Intestinal Cytochrome P450 3A and 2B6 in the Metabolism, Disposition, and Miotic Effects of Methadone","volume":"76","author":"Kharasch","year":"2004","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/S0169-409X(02)00066-2","article-title":"Genetic Contribution to Variable Human CYP3A-Mediated Metabolism","volume":"54","author":"Lamba","year":"2002","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/cpt.113","article-title":"Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing","volume":"98","author":"Birdwell","year":"2015","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"235","DOI":"10.2217\/pgs-2020-0032","article-title":"Pharmacogenomics and Prescription Opioid Use","volume":"22","author":"Benjeddou","year":"2021","journal-title":"Pharmacogenomics"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1517\/phgs.5.3.243.29833","article-title":"Genetic Variability in CYP3A5 and Its Possible Consequences","volume":"5","author":"Xie","year":"2004","journal-title":"Pharmacogenomics"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1111\/bcp.13129","article-title":"A Review of Factors Explaining Variability in Fentanyl Pharmacokinetics; Focus on Implications for Cancer Patients","volume":"83","author":"Kuip","year":"2017","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"93","DOI":"10.2174\/157488407779422302","article-title":"The Pharmacogenetics of CYP2C9 and CYP2C19: Ethnic Variation and Clinical Significance","volume":"2","author":"Rosemary","year":"2007","journal-title":"Curr. Clin. Pharmacol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/S0022-3565(24)34944-4","article-title":"A Novel Transversion in the Intron 5 Donor Splice Junction of CYP2C19 and a Sequence Polymorphism in Exon 3 Contribute to the Poor Metabolizer Phenotype for the Anticonvulsant Drug S-Mephenytoin","volume":"290","author":"Ibeanu","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1002\/dta.1997","article-title":"Effects of CYP2C19 Variants on Methadone Metabolism in Vitro","volume":"9","author":"Lan","year":"2017","journal-title":"Drug Test. Anal."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s40291-013-0028-5","article-title":"Applications of CYP450 Testing in the Clinical Setting","volume":"17","author":"Samer","year":"2013","journal-title":"Mol. Diagn. Ther."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1744806916683182","DOI":"10.1177\/1744806916683182","article-title":"Association between UGT2B7 Gene Polymorphisms and Fentanyl Sensitivity in Patients Undergoing Painful Orthognathic Surgery","volume":"12","author":"Muraoka","year":"2016","journal-title":"Mol. Pain"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1186\/cc9783","article-title":"UDP Glucuronosyltransferase 2B7 Single Nucleotide Polymorphism (Rs7439366) Influences Heat Pain Response in Human Volunteers after i.v. Morphine Infusion","volume":"15","author":"Meissner","year":"2011","journal-title":"Crit. Care"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Satkunananthan, S.E., Suppiah, V., Toh, G.-T., and Yow, H.-Y. (2022). Pharmacogenomics of Cancer Pain Treatment Outcomes in Asian Populations: A Review. J. Pers. Med., 12.","DOI":"10.3390\/jpm12111927"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/papr.12152","article-title":"Influence of Uridine Diphosphate-Glucuronyltransferase 2B7 (UGT2B7) Variants on Postoperative Buprenorphine Analgesia","volume":"15","author":"Sastre","year":"2013","journal-title":"Pain Pract."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.4103\/1119-3077.269019","article-title":"Roles of UGT2B7 C802T Gene Polymorphism on the Efficacy of Morphine Treatment on Cancer Pain Among the Chinese Han Population","volume":"22","author":"Ning","year":"2019","journal-title":"Niger. J. Clin. Pract."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1111\/papr.12816","article-title":"Genetic Contribution in Low Back Pain: A Prospective Genetic Association Study","volume":"19","author":"Margarit","year":"2019","journal-title":"Pain Pract."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1007\/s00228-013-1523-7","article-title":"Genetic Variability at COMT but Not at OPRM1 and UGT2B7 Loci Modulates Morphine Analgesic Response in Acute Postoperative Pain","volume":"69","author":"Gregori","year":"2013","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1007\/s00520-018-4130-4","article-title":"The Impact of UGT2B7 C802T and CYP3A4*1G Polymorphisms on Pain Relief in Cancer Patients Receiving Oxycontin","volume":"26","author":"Li","year":"2018","journal-title":"Support. Care Cancer"},{"key":"ref_132","first-page":"278-e166","article-title":"Morphine Versus Oxycodone for Cancer Pain Using a Catechol-O-Methyltransferase Genotype Biomarker: A Multicenter, Randomized, Open-Label, Phase III Clinical Trial (RELIEF Study)","volume":"28","author":"Matsuoka","year":"2022","journal-title":"Oncologist"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1744806920908474","DOI":"10.1177\/1744806920908474","article-title":"COMT Gene Variants and \u0392-Endorphin Levels Contribute to Ethnic Differences in Experimental Pain Sensitivity","volume":"16","author":"Xu","year":"2020","journal-title":"Mol. Pain"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Khan, A. (2023). Unraveling Catechol-O-Methyltransferase Rs4680 SNP\u2019s Role in Patients\u2019 Response to Tramadol and Its Adverse Effects: A Pharmacogenetics Insight into Postoperative Pain Management. J. Clin. Med., 13.","DOI":"10.3390\/jcm13010249"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"e3374","DOI":"10.1002\/jgm.3374","article-title":"Genetic Variation in Catechol-O-methyltransferase Is Associated with Individual Differences in Conditioned Pain Modulation in Healthy Subjects","volume":"23","author":"Korczeniewska","year":"2021","journal-title":"J. Gene Med."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Vetterlein, A., Monzel, M., and Reuter, M. (2023). Are Catechol-O-Methyltransferase Gene Polymorphisms Genetic Markers for Pain Sensitivity After All?\u2014A Review and Meta-Analysis. Neurosci. Biobehav. Rev., 148.","DOI":"10.1016\/j.neubiorev.2023.105112"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/s11912-020-0865-4","article-title":"Pharmacogenomics of Pain Management: The Impact of Specific Biological Polymorphisms on Drugs and Metabolism","volume":"22","author":"Cornett","year":"2020","journal-title":"Curr. Oncol. Rep."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"355","DOI":"10.3892\/ol.2023.13941","article-title":"Novel Single Nucleotide Polymorphism Biomarkers to Predict Opioid Effects for Cancer Pain","volume":"26","author":"Fujita","year":"2023","journal-title":"Oncol. Lett."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Ferrera, D., Mercado, F., Pel\u00e1ez, I., Mart\u00ednez-\u00cd\u00f1igo, D., Fernandes-Magalhaes, R., Barjola, P., \u00c9cija, C., D\u00edaz-Gil, G., and G\u00f3mez-Esquer, F. (2021). Fear of Pain Moderates the Relationship Between Self-Reported Fatigue and Methionine Allele of Catechol-O-Methyltransferase Gene in Patients with Fibromyalgia. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0250547"},{"key":"ref_140","first-page":"S521","article-title":"OPRM1 and ABCB1 Polymorphisms and Their Effect on Postoperative Pain Relief with Piritramide","volume":"64","author":"Perlik","year":"2015","journal-title":"Physiol. Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1515\/prilozi-2016-0019","article-title":"Association of Single-Nucleotide Polymorhism C3435T in the ABCB1 Gene with Opioid Sensitivity in Treatment of Postoperative Pain","volume":"37","author":"Nojkov","year":"2016","journal-title":"Prilozi"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.2217\/pgs-2021-0079","article-title":"Effects of Genetic Polymorphisms of ABCB1 on the Efficacy of Anesthetic and Analgesic Agents: A Systematic Review","volume":"22","author":"Liew","year":"2021","journal-title":"Pharmacogenomics"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"7","DOI":"10.2174\/1876386302013010007","article-title":"The Impact of Opioid Analgesics and the Pharmacogenomics of ABCB1 in Opioid Dependence and Pharmacotherapies: A Short Review","volume":"13","author":"Parchure","year":"2020","journal-title":"Open Pain J."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/tpj.2014.56","article-title":"Opioid-Induced Respiratory Depression: ABCB1 Transporter Pharmacogenetics","volume":"15","author":"Sadhasivam","year":"2014","journal-title":"Pharmacogenomics J."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Yang, J. (2023). Study on the Association Between Adverse Drug Reactions to Opioids and Gene Polymorphisms: A Case-Case\u2013Control Study. BMC Pharmacol. Toxicol., 24.","DOI":"10.1186\/s40360-023-00708-4"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1373\/jalm.2017.023150","article-title":"Pharmacogenetics of Opioid Use and Implications for Pain Management","volume":"2","author":"Nerenz","year":"2018","journal-title":"J. Appl. Lab. Med."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1093\/pm\/pnw317","article-title":"Pharmacogenomics and Patient Treatment Parameters to Opioid Treatment in Chronic Pain: A Focus on Morphine, Oxycodone, Tramadol, and Fentanyl","volume":"18","author":"Lloyd","year":"2017","journal-title":"Pain Med."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1007\/s43440-023-00455-7","article-title":"Effect of Common OPRM1, COMT, SLC6A4, ABCB1, and CYP2B6 Polymorphisms on Perioperative Analgesic and Propofol Demands on Patients Subjected to Thyroidectomy Surgery","volume":"75","author":"Soultati","year":"2023","journal-title":"Pharmacol. Rep."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"e86","DOI":"10.1016\/j.clinthera.2021.03.005","article-title":"Influence of Genetic Polymorphisms on the Response to Tramadol, Ibuprofen, and the Combination in Patients with Moderate to Severe Pain After Dental Surgery","volume":"43","author":"Borobia","year":"2021","journal-title":"Clin. Ther."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1097\/AJP.0000000000000167","article-title":"Genetic Polymorphisms in the Dopamine Receptor 2 Predict Acute Pain Severity After Motor Vehicle Collision","volume":"31","author":"Qadri","year":"2015","journal-title":"Clin. J. Pain"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Horjales-Ara\u00fajo, E., and Dahl, J.B. (2015). Is the Experience of Thermal Pain Genetics Dependent?. Biomed Res. Int., 2015.","DOI":"10.1155\/2015\/349584"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1016\/j.pain.2014.08.029","article-title":"Variation in the Dopamine D2 Receptor Gene Plays a Key Role in Human Pain and Its Modulation by Transcranial Magnetic Stimulation","volume":"155","author":"Lindholm","year":"2014","journal-title":"PAIN\u00ae"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"S787","DOI":"10.4103\/jpbs.JPBS_248_19","article-title":"Influence of DRD2 Polymorphisms on the Clinical Outcomes of Opioiddependent Patients on Methadone Maintenance Therapy","volume":"12","author":"Zahari","year":"2020","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/ajmg.b.10005","article-title":"D2 Dopamine Receptor Gene in Psychiatric and Neurologic Disorders and Its Phenotypes","volume":"116","author":"Noble","year":"2003","journal-title":"Am. J. Med. Genet. Part B Neuropsychiatr. Genet."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"E3441","DOI":"10.1073\/pnas.1602070113","article-title":"Morphine Paradoxically Prolongs Neuropathic Pain in Rats by Amplifying Spinal NLRP3 Inflammasome Activation","volume":"113","author":"Grace","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s10787-023-01402-x","article-title":"NLRs and Inflammasome Signaling in Opioid-Induced Hyperalgesia and Tolerance","volume":"32","author":"Zare","year":"2023","journal-title":"Inflammopharmacology"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"175901","DOI":"10.1016\/j.ejphar.2023.175901","article-title":"NLR Family Pyrin Domain Containing 3 (NLRP3) Inflammasomes and Peripheral Neuropathic Pain\u2014Emphasis on microRNAs (miRNAs) as Important Regulators","volume":"955","author":"Basu","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"4157","DOI":"10.7150\/ijbs.86492","article-title":"The PTGS2\/COX2-PGE2 Signaling Cascade in Inflammation: Pro or Anti? A Case Study with Type 1 Diabetes Mellitus","volume":"19","author":"Lorenzo","year":"2023","journal-title":"Int. J. Biol. Sci."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.acpain.2006.08.025","article-title":"Genetically Mediated Interindividual Variation in Analgesic Responses to Cyclooxygenase Inhibitory Drugs","volume":"8","author":"Lee","year":"2006","journal-title":"Acute Pain"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"142","DOI":"10.5055\/jom.2012.0108","article-title":"Affect of Genetic Polymorphisms on Pain Perception and Pain Management in Lung Cancer Survivors","volume":"8","year":"2012","journal-title":"J. Opioid Manag."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1111\/jdi.13938","article-title":"Sinomenine Alleviates Diabetic Peripheral Neuropathic Pain Through Inhibition of the Inositol-requiring Enzyme\u20091 Alpha\u2013X-box Binding Protein\u20091 Pathway by Downregulating Prostaglandin-endoperoxide Synthase\u20092","volume":"14","author":"Chen","year":"2023","journal-title":"J. Diabetes Investig."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"He, Z., Wen, B., Xu, L., and Huang, Y. (2023). Identification of Potential Inflammation-Related Genes and Key Pathways Associated with Complex Regional Pain Syndrome. Biomolecules, 13.","DOI":"10.3390\/biom13050772"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.prostaglandins.2015.01.001","article-title":"Atf3 Negatively Regulates Ptgs2\/Cox2 Expression During Acute Inflammation","volume":"116\u2013117","author":"Hellmann","year":"2015","journal-title":"Prostaglandins Other Lipid Mediat."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/5\/863\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:46:18Z","timestamp":1760028378000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/5\/863"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,3]]},"references-count":163,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["cancers17050863"],"URL":"https:\/\/doi.org\/10.3390\/cancers17050863","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,3]]}}}