Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Pain Biomarkers in Cancer: An Overview

Author(s): Fabrizio Calapai, Epifanio Mondello, Carmen Mannucci, Emanuela E. Sorbara, Sebastiano Gangemi, Domenico Quattrone, Gioacchino Calapai* and Luigi Cardia

Volume 27 , Issue 2 , 2021

Published on: 02 November, 2020

Page: [293 - 304] Pages: 12

DOI: 10.2174/1381612826666201102103520

Price: $65

Abstract

Background: Pain is a common symptom in oncologic patients and its management is generally guided with reference to pain individually perceived by patients and expressed through self-reported scales. However, the utility of these tools is limited as it strongly depends on patients’ opinions. For this reason, more objective instruments are desirable.

Objective: In this overview, scientific articles indicating potential markers to be used for pain management in cancer were collected and discussed.

Methods: Research was performed on principal electronic scientific databases by using the words “pain”, “cancer”, “markers” and “biomarkers” as the main keywords, and findings describing potential biomarkers for the management of cancer pain were reported.

Results: Studies on pain markers not specific for cancer typology (inflammatory, genetic markers predicting response to analgesic drugs, neuroimaging markers) and pain markers for specific types of cancer (bone cancer, breast cancer, lung cancer, head and neck cancer, prostate cancer, cancer in pediatrics) have been presented and commented on.

Conclusion: This overview supports the view of the involvement of inflammatory mediators in the mechanisms underlying cancer pain. Only a small amount of data from research up till today is available on markers that can help in the management of pain, except for pro-inflammatory cytokines and other inflammatory indexes such as C-reactive protein (CRP). However, biomarkers are a promising strategy useful to predict pain intensity and to objectively quantify analgesic response in guiding decisions regarding individual-tailored treatments for cancer patients.

Keywords: Cancer pain, pain diagnosis, analgesia, biomarkers, C-reactive protein, pro-inflammatory cytokines.

[1]
Reilly CM, Bruner DW, Mitchell SA, et al. A literature synthesis of symptom prevalence and severity in persons receiving active cancer treatment. Support Care Cancer 2013; 21: 1525-50.
[http://dx.doi.org/10.1007/s00520-012-1688-0]
[2]
Greco MT, Roberto A, Corli O, et al. Quality of cancer pain management: an update of a systematic review of undertreatment of patients with cancer. J Clin Oncol 2014; 32(36): 4149-54.
[http://dx.doi.org/10.1200/JCO.2014.56.0383] [PMID: 25403222]
[3]
Schmidt BL, Hamamoto DT, Simone DA, Wilcox GL. Mechanism of cancer pain. Mol Interv 2010; 10(3): 164-78.
[http://dx.doi.org/10.1124/mi.10.3.7] [PMID: 20539035]
[4]
Hjermstad MJ, Fayers PM, Haugen DF, et al. European Palliative Care Research Collaborative (EPCRC). Studies comparing Numerical Rating Scales, Verbal Rating Scales, and Visual Analogue Scales for assessment of pain intensity in adults: a systematic literature review. J Pain Symptom Manage 2011; 41(6): 1073-93.
[http://dx.doi.org/10.1016/j.jpainsymman.2010.08.016] [PMID: 21621130]
[5]
Te Boveldt N, Vernooij-Dassen M, Burger N, Ijsseldijk M, Vissers K, Engels Y. Pain and its interference with daily activities in medical oncology outpatients. Pain Physician 2013; 16(4): 379-89.
[PMID: 23877454]
[6]
Yennurajalingam S, Kang JH, Hui D, Kang DH, Kim SH, Bruera E. Clinical response to an outpatient palliative care consultation in patients with advanced cancer and cancer pain. J Pain Symptom Manage 2012; 44(3): 340-50.
[http://dx.doi.org/10.1016/j.jpainsymman.2011.09.014] [PMID: 22699092]
[7]
Brozek JL, Guyatt GH, Schünemann HJ. How a well-grounded minimal important difference can enhance transparency of labelling claims and improve interpretation of a patient reported outcome measure. Health Qual Life Outcomes 2006; 4: 69.
[http://dx.doi.org/10.1186/1477-7525-4-69] [PMID: 17005037]
[8]
Gerlinger C, Schumacher U, Faustmann T, Colligs A, Schmitz H, Seitz C. Defining a minimal clinically important difference for endometriosis-associated pelvic pain measured on a visual analog scale: analyses of two placebo-controlled, randomized trials. Health Qual Life Outcomes 2010; 8: 138.
[http://dx.doi.org/10.1186/1477-7525-8-138] [PMID: 21106059]
[9]
Arthur J, Tanco K, Park M, et al. Personalized Pain Goal as an Outcome Measure in Routine Cancer Pain Assessment. J Pain Symptom Manage 2018; 56(1): 80-7.
[http://dx.doi.org/10.1016/j.jpainsymman.2018.03.004] [PMID: 29526610]
[10]
Kelley KW, Bluthe R, Dantzer R, et al. Cytokine-induced sickness behavior. Brain Behav Immun 2003; 17: 112-8.
[http://dx.doi.org/10.1016/S0889-1591(02)00077-6]
[11]
Thacker MA, Clark AK, Marchand F, McMahon SB. Pathophysiology of peripheral neuropathic pain: immune cells and molecules. Anesth Analg 2007; 105(3): 838-47.
[http://dx.doi.org/10.1213/01.ane.0000275190.42912.37] [PMID: 17717248]
[12]
Fazzari J, Sidhu J, Motkur S, et al. Applying Serum Cytokine Levels to Predict Pain Severity in Cancer Patients. J Pain Res 2020; 13: 313-21.
[http://dx.doi.org/10.2147/JPR.S227175] [PMID: 32104053]
[13]
Laird BJ, McMillan DC, Fayers P, et al. The systemic inflammatory response and its relationship to pain and other symptoms in advanced cancer. Oncologist 2013; 18(9): 1050-5.
[http://dx.doi.org/10.1634/theoncologist.2013-0120] [PMID: 23966223]
[14]
Rokyta R, Haklova O, Yamamotova A. Assessment of chronic benign and cancer pain using blood plasma biomarkers. Neuroendocrinol Lett 2009; 30(5): 637-42.
[PMID: 20035266]
[15]
Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell 2009; 139(2): 267-84.
[http://dx.doi.org/10.1016/j.cell.2009.09.028] [PMID: 19837031]
[16]
Vanderwall AG, Milligan ED. Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management. Front Immunol 2019; 10: 3009.
[http://dx.doi.org/10.3389/fimmu.2019.03009] [PMID: 31921220]
[17]
Zelenka M, Schäfers M, Sommer C. Intraneural injection of interleukin-1beta and tumor necrosis factor-alpha into rat sciatic nerve at physiological doses induces signs of neuropathic pain. Pain 2005; 116(3): 257-63.
[http://dx.doi.org/10.1016/j.pain.2005.04.018] [PMID: 15964142]
[18]
Uçeyler N, Valenza R, Stock M, Schedel R, Sprotte G, Sommer C. Reduced levels of antiinflammatory cytokines in patients with chronic widespread pain. Arthritis Rheum 2006; 54(8): 2656-64.
[http://dx.doi.org/10.1002/art.22026] [PMID: 16871547]
[19]
Uçeyler N, Eberle T, Rolke R, Birklein F, Sommer C. Differential expression patterns of cytokines in complex regional pain syndrome. Pain 2007; 132(1-2): 195-205.
[http://dx.doi.org/10.1016/j.pain.2007.07.031] [PMID: 17890011]
[20]
Breitbart W, Rosenfeld B, Tobias K, et al. Depression, cytokines, and pancreatic cancer. Psychooncology 2014; 23(3): 339-45.
[http://dx.doi.org/10.1002/pon.3422] [PMID: 24136882]
[21]
Makimura C, Arao T, Matsuoka H, et al. Prospective study evaluating the plasma concentrations of twenty-six cytokines and response to morphine treatment in cancer patients. Anticancer Res 2011; 31(12): 4561-8.
[PMID: 22199331]
[22]
Paulsen Ø, Laird B, Aass N, et al. The relationship between pro-inflammatory cytokines and pain, appetite and fatigue in patients with advanced cancer. PLoS One 2017; 12(5)e0177620
[http://dx.doi.org/10.1371/journal.pone.0177620] [PMID: 28542626]
[23]
Heitzer E, Sandner-Kiesling A, Schippinger W, et al. IL-7, IL-18, MCP-1, MIP1-β, and OPG as biomarkers for pain treatment response in patients with cancer. Pain Physician 2012; 15(6): 499-510.
[PMID: 23159968]
[24]
Kwekkeboom KL, Tostrud L, Costanzo E, et al. The Role of Inflammation in the Pain, Fatigue, and Sleep Disturbance Symptom Cluster in Advanced Cancer. J Pain Symptom Manage 2018; 55(5): 1286-95.
[http://dx.doi.org/10.1016/j.jpainsymman.2018.01.008] [PMID: 29360570]
[25]
Sehgal A, Whiteside TL, Boyiadzis M. Programmed death-1 checkpoint blockade in acute myeloid leukemia. Expert Opin Biol Ther 2015; 15(8): 1191-203.
[http://dx.doi.org/10.1517/14712598.2015.1051028] [PMID: 26036819]
[26]
Ren D, Hua Y, Yu B, et al. Predictive biomarkers and mechanisms underlying resistance to PD1/PD-L1 blockade cancer immunotherapy. Mol Cancer 2020; 19(1): 19.
[http://dx.doi.org/10.1186/s12943-020-1144-6] [PMID: 32000802]
[27]
Zhu X, Lang J. Soluble PD-1 and PD-L1: predictive and prognostic significance in cancer. Oncotarget 2017; 8(57): 97671-82.
[http://dx.doi.org/10.18632/oncotarget.18311] [PMID: 29228642]
[28]
Zhang J, Zhang H, Luo Y. Association Between Activation of the Programmed Cell Death-1 (PD-1)/Programmed Death-Ligand 1 (PD-L1) Pathway and Pain in Patients with Cancer. Med Sci Monit 2019; 25: 1275-82.
[http://dx.doi.org/10.12659/MSM.912632] [PMID: 30771277]
[29]
Laganà AS, Vitale SG, Nigro A, et al. Pleiotropic Actions of Peroxisome Proliferator-Activated Receptors (PPARs) in Dysregulated Metabolic Homeostasis, Inflammation and Cancer: Current Evidence and Future Perspectives. Int J Mol Sci 2016; 17(7): 999.
[http://dx.doi.org/10.3390/ijms17070999] [PMID: 27347932]
[30]
Vitale SG, Laganà AS, Nigro A, et al. Peroxisome Proliferator-Activated Receptor Modulation during Metabolic Diseases and Cancers: Master and Minions. PPAR Res 2016; 20166517313
[http://dx.doi.org/10.1155/2016/6517313] [PMID: 28115924]
[31]
Okine BN, Gaspar JC, Finn DP. PPARs and pain. Br J Pharmacol 2019; 176(10): 1421-42.
[http://dx.doi.org/10.1111/bph.14339] [PMID: 29679493]
[32]
Cornett EM, Carroll Turpin MA, Pinner A, et al. Pharmacogenomics of Pain Management: The Impact of Specific Biological Polymorphisms on Drugs and Metabolism. Curr Oncol Rep 2020; 22(2): 18.
[http://dx.doi.org/10.1007/s11912-020-0865-4] [PMID: 32030524]
[33]
Matsuoka H, Arao T, Makimura C, et al. Expression changes in arrestin β 1 and genetic variation in catechol-O-methyltransferase are biomarkers for the response to morphine treatment in cancer patients. Oncol Rep 2012; 27(5): 1393-9.
[PMID: 22293824]
[34]
Hosák L. Role of the COMT gene Val158Met polymorphism in mental disorders: a review. Eur Psychiatry 2007; 22(5): 276-81.
[http://dx.doi.org/10.1016/j.eurpsy.2007.02.002] [PMID: 17419009]
[35]
Klepstad P, Fladvad T, Skorpen F, et al. European Palliative Care Research Collaborative (EPCRC); European Association for Palliative Care Research Network. Influence from genetic variability on opioid use for cancer pain: a European genetic association study of 2294 cancer pain patients. Pain 2011; 152(5): 1139-45.
[http://dx.doi.org/10.1016/j.pain.2011.01.040] [PMID: 21398039]
[36]
Fladvad T, Fayers P, Skorpen F, Kaasa S, Klepstad P. Lack of association between genetic variability and multiple pain-related outcomes in a large cohort of patients with advanced cancer: the European Pharmacogenetic Opioid Study (EPOS). BMJ Support Palliat Care 2012; 2(4): 351-5.
[http://dx.doi.org/10.1136/bmjspcare-2012-000212] [PMID: 24654220]
[37]
Owusu Obeng A, Hamadeh I, Smith M. Review of Opioid Pharmacogenetics and Considerations for Pain Management. Pharmacotherapy 2017; 37(9): 1105-21.
[http://dx.doi.org/10.1002/phar.1986] [PMID: 28699646]
[38]
Gretton SK, Ross JR, Rutter D, et al. Plasma morphine and metabolite concentrations are associated with clinical effects of morphine in cancer patients. J Pain Symptom Manage 2013; 45(4): 670-80.
[http://dx.doi.org/10.1016/j.jpainsymman.2012.03.015] [PMID: 22995672]
[39]
Mackey S, Greely HT, Martucci KT. Neuroimaging-based pain biomarkers: definitions, clinical and research applications, and evaluation frameworks to achieve personalized pain medicine. Pain Rep 2019; 4(4)e762
[http://dx.doi.org/10.1097/PR9.0000000000000762] [PMID: 31579854]
[40]
Ferrari M, Mottola L, Quaresima V. Principles, techniques, and limitations of near infrared spectroscopy. Can J Appl Physiol 2004; 29(4): 463-87.
[http://dx.doi.org/10.1139/h04-031] [PMID: 15328595]
[41]
Fernandez Rojas R, Huang X, Ou KL. A Machine Learning Approach for the Identification of a Biomarker of Human Pain using fNIRS. Sci Rep 2019; 9(1): 5645.
[http://dx.doi.org/10.1038/s41598-019-42098-w] [PMID: 30948760]
[42]
Freund P, Schneider T, Nagy Z, et al. Degeneration of the injured cervical cord is associated with remote changes in corticospinal tract integrity and upper limb impairment. PLoS One 2012; 7(12)e51729
[http://dx.doi.org/10.1371/journal.pone.0051729] [PMID: 23251612]
[43]
Vedantam A, Hou P, Chi TL, Dougherty PM, Hess KR, Viswanathan A. Use of Spinal Cord Diffusion Tensor Imaging to Quantify Neural Ablation and Evaluate Outcome after Percutaneous Cordotomy for Intractable Cancer Pain. Stereotact Funct Neurosurg 2017; 95(1): 34-9.
[http://dx.doi.org/10.1159/000453279] [PMID: 28088799]
[44]
Grond S, Zech D, Diefenbach C, Radbruch L, Lehmann KA. Assessment of cancer pain: a prospective evaluation in 2266 cancer patients referred to a pain service. Pain 1996; 64(1): 107-14.
[http://dx.doi.org/10.1016/0304-3959(95)00076-3] [PMID: 8867252]
[45]
Mantyh P. Bone cancer pain: causes, consequences, and therapeutic opportunities. Pain 2013; 154(Suppl. 1): S54-62.
[http://dx.doi.org/10.1016/j.pain.2013.07.044] [PMID: 23916671]
[46]
Laird BJ, Scott AC, Colvin LA, et al. Cancer pain and its relationship to systemic inflammation: an exploratory study. Pain 2011; 152(2): 460-3.
[http://dx.doi.org/10.1016/j.pain.2010.10.035] [PMID: 21159432]
[47]
Aielli F, Ponzetti M, Rucci N. Bone Metastasis Pain, from the Bench to the Bedside. Int J Mol Sci 2019; 20(2): 280.
[http://dx.doi.org/10.3390/ijms20020280] [PMID: 30641973]
[48]
Mercadante S, Arcuri E. Breakthrough pain in cancer patients: pathophysiology and treatment. Cancer Treat Rev 1998; 24(6): 425-32.
[http://dx.doi.org/10.1016/S0305-7372(98)90005-6] [PMID: 10189409]
[49]
Caraceni A, Martini C, Zecca E, et al. Working Group of an IASP Task Force on Cancer Pain. Breakthrough pain characteristics and syndromes in patients with cancer pain. An international survey. Palliat Med 2004; 18(3): 177-83.
[http://dx.doi.org/10.1191/0269216304pm890oa] [PMID: 15198130]
[50]
Chiu L, Wong E, DeAngelis C, et al. Use of urinary markers in cancer setting: A literature review. J Bone Oncol 2015; 4(1): 18-23.
[http://dx.doi.org/10.1016/j.jbo.2015.01.002] [PMID: 26579485]
[51]
Zafeirakis A, Papatheodorou G, Arhontakis A, Gouliamos A, Vlahos L, Limouris GS. Predictive implications of bone turnover markers after palliative treatment with (186)Re-HEDP in hormone-refractory prostate cancer patients with painful osseous metastases. Eur J Nucl Med Mol Imaging 2010; 37(1): 103-13.
[http://dx.doi.org/10.1007/s00259-009-1243-5] [PMID: 19662405]
[52]
McDonald R, Ding K, Brundage M, et al. Effect of radiotherapy on painful bone metastases: a secondary analysis of the NCIC clinical trials group symptom control trial SC.23. JAMA Oncol 2017; 3(7): 953-9.
[http://dx.doi.org/10.1001/jamaoncol.2016.6770] [PMID: 28196208]
[53]
Chow E, DeAngelis C, Chen BE, et al. Effect of re-irradiation for painful bone metastases on urinary markers of osteoclast activity (NCIC CTG SC.20U). Radiother Oncol 2015; 115(1): 141-8.
[http://dx.doi.org/10.1016/j.radonc.2015.02.025] [PMID: 25782738]
[54]
Baamonde A, Curto-Reyes V, Juárez L, Meana A, Hidalgo A, Menéndez L. Antihyperalgesic effects induced by the IL-1 receptor antagonist anakinra and increased IL-1beta levels in inflamed and osteosarcoma-bearing mice. Life Sci 2007; 81(8): 673-82.
[http://dx.doi.org/10.1016/j.lfs.2007.07.003] [PMID: 17692876]
[55]
Geis C, Graulich M, Wissmann A, et al. Evoked pain behavior and spinal glia activation is dependent on tumor necrosis factor receptor 1 and 2 in a mouse model of bone cancer pain. Neuroscience 2010; 169(1): 463-74.
[http://dx.doi.org/10.1016/j.neuroscience.2010.04.022] [PMID: 20417692]
[56]
Sevcik MA, Ghilardi JR, Peters CM, et al. Anti-NGF therapy profoundly reduces bone cancer pain and the accompanying increase in markers of peripheral and central sensitization. Pain 2005; 115(1-2): 128-41.
[http://dx.doi.org/10.1016/j.pain.2005.02.022] [PMID: 15836976]
[57]
Chen J, Cong X, Zhan X, Zhou Z, Zheng W. Effects of Parecoxib on Pain Threshold and Inflammatory Factors IL-1β, IL-6 and TNF-α in Spinal Cord of Rats with Bone Cancer Pain. J Coll Physicians Surg Pak 2019; 29(6): 528-31.
[http://dx.doi.org/10.29271/jcpsp.2019.06.528] [PMID: 31133150]
[58]
Hu JH, Zheng XY, Yang JP, Wang LN, Ji FH. Involvement of spinal monocyte chemoattractant protein-1 (MCP-1) in cancer-induced bone pain in rats. Neurosci Lett 2012; 517(1): 60-3.
[http://dx.doi.org/10.1016/j.neulet.2012.04.026] [PMID: 22531750]
[59]
Roldan CJ, Abdi S. Quantitative sensory testing in pain management. Pain Manag 2015; 5(6): 483-91.
[http://dx.doi.org/10.2217/pmt.15.37] [PMID: 26399563]
[60]
Treede RD. The role of quantitative sensory testing in the prediction of chronic pain. Pain 2019; 160(Suppl. 1): S66-9.
[http://dx.doi.org/10.1097/j.pain.0000000000001544] [PMID: 31008852]
[61]
Scott AC, McConnell S, Laird B, Colvin L, Fallon M. Quantitative Sensory Testing to assess the sensory characteristics of cancer-induced bone pain after radiotherapy and potential clinical biomarkers of response. Eur J Pain 2012; 16(1): 123-33.
[http://dx.doi.org/10.1016/j.ejpain.2011.05.002] [PMID: 21658980]
[62]
Martland ME, Rashidi AS, Bennett MI, et al. The use of quantitative sensory testing in cancer pain assessment: A systematic review. Eur J Pain 2020; 24(4): 669-84.
[http://dx.doi.org/10.1002/ejp.1520] [PMID: 31823467]
[63]
López-González MJ, Landry M, Favereaux A. MicroRNA and chronic pain: From mechanisms to therapeutic potential. Pharmacol Ther 2017; 180: 1-15.
[http://dx.doi.org/10.1016/j.pharmthera.2017.06.001] [PMID: 28579386]
[64]
Kiyosawa N, Watanabe K, Toyama K, Ishizuka H. Circulating miRNA Signature as a Potential Biomarker for the Prediction of Analgesic Efficacy of Hydromorphone. Int J Mol Sci 2019; 20(7): 1665.
[http://dx.doi.org/10.3390/ijms20071665] [PMID: 30987164]
[65]
Hang LH, Li SN, Luo H, et al. Connexin 43 Mediates CXCL12 Production from Spinal Dorsal Horn to Maintain Bone Cancer Pain in Rats. Neurochem Res 2016; 41(5): 1200-8.
[http://dx.doi.org/10.1007/s11064-015-1815-7] [PMID: 26721509]
[66]
Agalave NM, Svensson CI. Extracellular high-mobility group box 1 protein (HMGB1) as a mediator of persistent pain. Mol Med 2015; 20: 569-78.
[http://dx.doi.org/10.2119/molmed.2014.00176] [PMID: 25222915]
[67]
An K, Rong H, Ni H, et al. Spinal PKC activation - Induced neuronal HMGB1 translocation contributes to hyperalgesia in a bone cancer pain model in rats. Exp Neurol 2018; 303: 80-94.
[http://dx.doi.org/10.1016/j.expneurol.2018.02.003] [PMID: 29428215]
[68]
Liu C, Yang J, Liu H, Xia T, Zhang F. miR-300 mitigates cancer-induced bone pain through targeting HMGB1 in rat models. Genes Genomics 2020; 42(3): 309-16.
[http://dx.doi.org/10.1007/s13258-019-00904-9] [PMID: 31872385]
[69]
Yang H, Yan H, Li X, et al. Inhibition of Connexin 43 and Phosphorylated NR2B in Spinal Astrocytes Attenuates Bone Cancer Pain in Mice. Front Cell Neurosci 2018; 12: 129.
[http://dx.doi.org/10.3389/fncel.2018.00129] [PMID: 29867362]
[70]
Furfari A, Wan BA, Ding K, et al. Genetic biomarkers associated with pain flare and dexamethasone response following palliative radiotherapy in patients with painful bone metastases. Ann Palliat Med 2017; 6(Suppl. 2): S240-7.
[http://dx.doi.org/10.21037/apm.2017.09.04] [PMID: 29156912]
[71]
Bushehri A, Chow E, Zhang L, et al. Urinary cytokines/chemokines pattern in patients with painful bone metastases undergoing external beam radiotherapy experiencing pain flare. Ann Palliat Med 2016; 5(2): 107-15.
[http://dx.doi.org/10.21037/apm.2016.03.04] [PMID: 27121738]
[72]
Bushehri A, Czarnota G, Zhang L, et al. Urinary cytokines/chemokines after magnetic resonance-guided high intensity focused ultrasound for palliative treatment of painful bone metastases. Ann Palliat Med 2017; 6(1): 36-54.
[http://dx.doi.org/10.21037/apm.2016.12.06] [PMID: 28209068]
[73]
Milligan ED, Sloane EM, Watkins LR. Glia in pathological pain: a role for fractalkine. J Neuroimmunol 2008; 198(1-2): 113-20.
[http://dx.doi.org/10.1016/j.jneuroim.2008.04.011] [PMID: 18547654]
[74]
Gao YJ, Ji RR. Targeting astrocyte signaling for chronic pain. Neurotherapeutics 2010; 7(4): 482-93.
[http://dx.doi.org/10.1016/j.nurt.2010.05.016] [PMID: 20880510]
[75]
Ji RR, Donnelly CR, Nedergaard M. Astrocytes in chronic pain and itch. Nat Rev Neurosci 2019; 20(11): 667-85.
[http://dx.doi.org/10.1038/s41583-019-0218-1] [PMID: 31537912]
[76]
Ducourneau VR, Dolique T, Hachem-Delaunay S, et al. Cancer pain is not necessarily correlated with spinal overexpression of reactive glia markers. Pain 2014; 155(2): 275-91.
[http://dx.doi.org/10.1016/j.pain.2013.10.008] [PMID: 24120461]
[77]
Liu H, Dong WY, Wang JB, et al. Association between salivary α-amylase activity and pain relief scale scores in cancer patients with bone metastases treated with radiotherapy. Chin Med J (Engl) 2013; 126(23): 4444-7.
[PMID: 24286404]
[78]
Kane CM, Hoskin P, Bennett MI. Cancer induced bone pain. BMJ 2015; 350: h315.
[http://dx.doi.org/10.1136/bmj.h315] [PMID: 25633978]
[79]
Wong R, Wiffen PJ. Bisphosphonates for the relief of pain secondary to bone metastases. Cochrane Database Syst Rev 2002; (2): CD002068
[http://dx.doi.org/10.1002/14651858.CD002068] [PMID: 12076438]
[80]
Sikandar S, Patel R, Patel S, Sikander S, Bennett DL, Dickenson AH. Genes, molecules and patients-emerging topics to guide clinical pain research. Eur J Pharmacol 2013; 716(1-3): 188-202.
[http://dx.doi.org/10.1016/j.ejphar.2013.01.069] [PMID: 23500200]
[81]
Major PP, Cook R. Efficacy of bisphosphonates in the management of skeletal complications of bone metastases and selection of clinical endpoints. Am J Clin Oncol 2002; 25(6)(Suppl. 1): S10-8.
[http://dx.doi.org/10.1097/00000421-200212001-00003] [PMID: 12562046]
[82]
Buehlmann D, Grandjean J, Xandry J, Rudin M. Longitudinal resting-state functional magnetic resonance imaging in a mouse model of metastatic bone cancer reveals distinct functional reorganizations along a developing chronic pain state. Pain 2018; 159(4): 719-27.
[http://dx.doi.org/10.1097/j.pain.0000000000001148] [PMID: 29319607]
[83]
Gardner K, Laird BJA, Fallon MT, Sande TA. A systematic review examining clinical markers and biomarkers of analgesic response to radiotherapy for cancer-induced bone pain. Crit Rev Oncol Hematol 2019; 133: 33-44.
[http://dx.doi.org/10.1016/j.critrevonc.2018.10.008] [PMID: 30661656]
[84]
Starkweather AR, Lyon DE, Schubert CM. Pain and inflammation in women with early-stage breast cancer prior to induction of chemotherapy. Biol Res Nurs 2013; 15(2): 234-41.
[http://dx.doi.org/10.1177/1099800411425857] [PMID: 22084403]
[85]
Lee E, Nelson OL, Puyana C, et al. Association between C-reactive protein and radiotherapy-related pain in a tri-racial/ethnic population of breast cancer patients: a prospective cohort study. Breast Cancer Res 2019; 21(1): 70.
[http://dx.doi.org/10.1186/s13058-019-1151-y] [PMID: 31138314]
[86]
Miller AH, Ancoli-Israel S, Bower JE, Capuron L, Irwin MR. Neuroendocrine-immune mechanisms of behavioral comorbidities in patients with cancer. J Clin Oncol 2008; 26(6): 971-82.
[http://dx.doi.org/10.1200/JCO.2007.10.7805] [PMID: 18281672]
[87]
Dantzer R, O’Connor JCF, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 2008; 9(1): 46-56.
[http://dx.doi.org/10.1038/nrn2297] [PMID: 18073775]
[88]
Thornton LM, Andersen BL, Blakely WP. The pain, depression, and fatigue symptom cluster in advanced breast cancer: covariation with the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Health Psychol 2010; 29(3): 333-7.
[http://dx.doi.org/10.1037/a0018836] [PMID: 20496988]
[89]
Schreiber KL, Martel MO, Shnol H, et al. Persistent pain in postmastectomy patients: comparison of psychophysical, medical, surgical, and psychosocial characteristics between patients with and without pain. Pain 2013; 154(5): 660-8.
[http://dx.doi.org/10.1016/j.pain.2012.11.015] [PMID: 23290256]
[90]
Nissenbaum J, Devor M, Seltzer Z, et al. Susceptibility to chronic pain following nerve injury is genetically affected by CACNG2. Genome Res 2010; 20(9): 1180-90.
[http://dx.doi.org/10.1101/gr.104976.110] [PMID: 20688780]
[91]
Peciña M, Love T, Stohler CS, Goldman D, Zubieta JK. Effects of the Mu opioid receptor polymorphism (OPRM1 A118G) on pain regulation, placebo effects and associated personality trait measures. Neuropsychopharmacology 2015; 40(4): 957-65.
[http://dx.doi.org/10.1038/npp.2014.272] [PMID: 25308352]
[92]
Klepstad P, Rakvåg TT, Kaasa S, et al. The 118 A > G polymorphism in the human mu-opioid receptor gene may increase morphine requirements in patients with pain caused by malignant disease. Acta Anaesthesiol Scand 2004; 48(10): 1232-9.
[http://dx.doi.org/10.1111/j.1399-6576.2004.00517.x] [PMID: 15504181]
[93]
De Gregori M, Diatchenko L, Belfer I, Allegri M. OPRM1 receptor as new biomarker to help the prediction of post mastectomy pain and recurrence in breast cancer. Minerva Anestesiol 2015; 81(8): 894-900.
[PMID: 25300626]
[94]
Diaconu C, Pantis C, Cirimbei C, Bordea C, Gruia MI, Blidaru A. Pain-associated biomarkers in breast cancer. J Med Life 2015; 8(1): 32-6.
[PMID: 25914735]
[95]
Bortsov AV, Devor M, Kaunisto MA, et al. CACNG2 polymorphisms associate with chronic pain after mastectomy. Pain 2019; 160(3): 561-8.
[http://dx.doi.org/10.1097/j.pain.0000000000001432] [PMID: 30371558]
[96]
Reyes-Gibby CC, Spitz M, Wu X, et al. Cytokine genes and pain severity in lung cancer: exploring the influence of TNF-alpha-308 G/A IL6-174G/C and IL8-251T/A. Cancer Epidemiol Biomarkers Prev 2007; 16(12): 2745-51.
[http://dx.doi.org/10.1158/1055-9965.EPI-07-0651] [PMID: 18086782]
[97]
Reyes-Gibby CC, El Osta B, Spitz MR, et al. The influence of tumor necrosis factor-alpha -308 G/A and IL-6 -174 G/C on pain and analgesia response in lung cancer patients receiving supportive care. Cancer Epidemiol Biomarkers Prev 2008; 17(11): 3262-7.
[http://dx.doi.org/10.1158/1055-9965.EPI-08-0125] [PMID: 18990769]
[98]
Reyes-Gibby CC, Shete S, Yennurajalingam S, et al. Genetic and nongenetic covariates of pain severity in patients with adenocarcinoma of the pancreas: assessing the influence of cytokine genes. J Pain Symptom Manage 2009; 38(6): 894-902.
[http://dx.doi.org/10.1016/j.jpainsymman.2009.04.019] [PMID: 19692203]
[99]
Reyes-Gibby CC, Spitz MR, Yennurajalingam S, et al. Role of inflammation gene polymorphisms on pain severity in lung cancer patients. Cancer Epidemiol Biomarkers Prev 2009; 18(10): 2636-42.
[http://dx.doi.org/10.1158/1055-9965.EPI-09-0426] [PMID: 19773451]
[100]
Epstein JB, Robertson M, Emerton S, Phillips N, Stevenson-Moore P. Quality of life and oral function in patients treated with radiation therapy for head and neck cancer. Head Neck 2001; 23(5): 389-98.
[http://dx.doi.org/10.1002/hed.1049] [PMID: 11295813]
[101]
Jablonska E, Piotrowski L, Grabowska Z. Serum Levels of IL-1b, IL-6, TNF-a, sTNF-RI and CRP in Patients with Oral Cavity Cancer. Pathol Oncol Res 1997; 3(2): 126-9.
[http://dx.doi.org/10.1007/BF02907807] [PMID: 11173639]
[102]
Gavrielatou N, Doumas S, Economopoulou P, Foukas PG, Psyrri A. Biomarkers for immunotherapy response in head and neck cancer. Cancer Treat Rev 2020; 84101977
[http://dx.doi.org/10.1016/j.ctrv.2020.101977] [PMID: 32018128]
[103]
Oliveira KG, von Zeidler SV, Lamas AZ, et al. Relationship of inflammatory markers and pain in patients with head and neck cancer prior to anticancer therapy. Braz J Med Biol Res 2014; 47(7): 600-4.
[http://dx.doi.org/10.1590/1414-431X20143599] [PMID: 25003634]
[104]
Enevoldsen FC, Sahana J, Wehland M, Grimm D, Infanger M, Krüger M. Endothelin Receptor Antagonists: Status Quo and Future Perspectives for Targeted Therapy. J Clin Med 2020; 9(3)E824
[http://dx.doi.org/10.3390/jcm9030824] [PMID: 32197449]
[105]
Viet CT, Schmidt BL. Biologic mechanisms of oral cancer pain and implications for clinical therapy. J Dent Res 2012; 91(5): 447-53.
[http://dx.doi.org/10.1177/0022034511424156] [PMID: 21972258]
[106]
McKenzie GA, Hinsley EE, Hunter K, Lambert DW. The endothelin axis in head and neck cancer: a promising therapeutic opportunity? J Oral Pathol Med 2014; 43(6): 395-404.
[http://dx.doi.org/10.1111/jop.12108] [PMID: 23957241]
[107]
Dunn MW. Prostate Cancer Screening. Semin Oncol Nurs 2017; 33(2): 156-64.
[http://dx.doi.org/10.1016/j.soncn.2017.02.003] [PMID: 28343840]
[108]
Kirby M, Hirst C, Crawford ED. Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract 2011; 65(11): 1180-92.
[http://dx.doi.org/10.1111/j.1742-1241.2011.02799.x] [PMID: 21995694]
[109]
Reza M, Ohlsson M, Kaboteh R, et al. Bone Scan Index as an Imaging Biomarker in Metastatic Castration-resistant Prostate Cancer: A Multicentre Study Based on Patients Treated with Abiraterone Acetate (Zytiga) in Clinical Practice. Eur Urol Focus 2016; 2(5): 540-6.
[http://dx.doi.org/10.1016/j.euf.2016.02.013] [PMID: 28723520]
[110]
Imbriaco M, Larson SM, Yeung HW, et al. A new parameter for measuring metastatic bone involvement by prostate cancer: the Bone Scan Index. Clin Cancer Res 1998; 4(7): 1765-72.
[PMID: 9676853]
[111]
Armstrong AJ, Anand A, Edenbrandt L, et al. Phase 3 Assessment of the Automated Bone Scan Index as a Prognostic Imaging Biomarker of Overall Survival in Men With Metastatic Castration-Resistant Prostate Cancer: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol 2018; 4(7): 944-51.
[http://dx.doi.org/10.1001/jamaoncol.2018.1093] [PMID: 29799999]
[112]
Schaake W, van der Schaaf A, van Dijk LV, van den Bergh ACM, Langendijk JA. Development of a prediction model for late urinary incontinence, hematuria, pain and voiding frequency among irradiated prostate cancer patients. PLoS One 2018; 13(7)e0197757
[http://dx.doi.org/10.1371/journal.pone.0197757] [PMID: 30016325]
[113]
Francini E, Gray KP, Xie W, et al. Time of metastatic disease presentation and volume of disease are prognostic for metastatic hormone sensitive prostate cancer (mHSPC). Prostate 2018; 78(12): 889-95.
[http://dx.doi.org/10.1002/pros.23645] [PMID: 29707790]
[114]
Richardson J, Smith JE, McCall G, Pilkington K. Hypnosis for procedure-related pain and distress in pediatric cancer patients: a systematic review of effectiveness and methodology related to hypnosis interventions. J Pain Symptom Manage 2006; 31(1): 70-84.
[http://dx.doi.org/10.1016/j.jpainsymman.2005.06.010] [PMID: 16442484]
[115]
Evans S, Seidman LC, Tsao JC, Lung KC, Zeltzer LK, Naliboff BD. Heart rate variability as a biomarker for autonomic nervous system response differences between children with chronic pain and healthy control children. J Pain Res 2013; 6: 449-57.
[PMID: 23788839]
[116]
Nater UM, Rohleder N. Salivary alpha-amylase as a non-invasive biomarker for the sympathetic nervous system: current state of research. Psychoneuroendocrinology 2009; 34(4): 486-96.
[http://dx.doi.org/10.1016/j.psyneuen.2009.01.014] [PMID: 19249160]
[117]
Payne LA, Hibel LC, Granger DA, Tsao JC, Zeltzer LK. Relationship of Salivary Alpha Amylase and Cortisol to Social Anxiety in Healthy Children Undergoing Laboratory Pain Tasks. J Child Adolesc Behav 2014; 21000129
[http://dx.doi.org/10.4172/2375-4494.1000129] [PMID: 25525630]
[118]
Jenkins BN, Granger DA, Roemer RJ, Martinez A, Torres TK, Fortier MA. Emotion regulation and positive affect in the context of salivary alpha-amylase response to pain in children with cancer. Pediatr Blood Cancer 2018; 65(6)e26973
[http://dx.doi.org/10.1002/pbc.26973] [PMID: 29350481]
[119]
Vitale SG, Capriglione S, Zito G, et al. Management of endometrial, ovarian and cervical cancer in the elderly: current approach to a challenging condition. Arch Gynecol Obstet 2019; 299(2): 299-315.
[http://dx.doi.org/10.1007/s00404-018-5006-z] [PMID: 30542793]
[120]
Lindemann K, Martinsson L, Kaasa S, Lindquist D. Elderly gynaecological cancer patients at risk for poor end of life care: a population-based study from the Swedish Register of Palliative Care. Acta Oncol 2020; 59(6): 636-43.
[http://dx.doi.org/10.1080/0284186X.2020.1744717] [PMID: 32238040]
[121]
Morotti M, Vincent K, Becker CM. Mechanisms of pain in endometriosis. Eur J Obstet Gynecol Reprod Biol 2017; 209: 8-13.
[http://dx.doi.org/10.1016/j.ejogrb.2016.07.497] [PMID: 27522645]
[122]
Li D, Puntillo K, Miaskowski C. A review of objective pain measures for use with critical care adult patients unable to self-report. J Pain 2008; 9(1): 2-10.
[http://dx.doi.org/10.1016/j.jpain.2007.08.009] [PMID: 17981512]
[123]
Golčić M, Dobrila-Dintinjana R, Golčić G, Pavlović-Ružić I, Gović-Golčić L. Do Physicians Underestimate Pain in Terminal Cancer Patients? A Prospective Study in a Hospice Setting. Clin J Pain 2018; 34(12): 1159-63.
[http://dx.doi.org/10.1097/AJP.0000000000000641] [PMID: 30028368]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy