• 1
    Riley J, Ross JR, Rutter D, Shah S, Gwilliam B, Wells AU, Welsh K. A retrospective study of the association between haematological and biochemical parameters and morphine intolerance in patients with cancer pain. Palliat Med 2004; 18: 1924.
  • 2
    Cherny N, Ripamonti C, Pereira J, Davis C, Fallon M, McQuay H, Mercadante S, Pasternak G, Ventafridda V. Strategies to manage the adverse effects of oral morphine: an evidence-based report. [Review] [172 refs]. J Clin Oncol 2001; 19: 25422554.
  • 3
    Riley J, Ross JR, Rutter D, Wells AU, Goller K, Du BR, Welsh K. No pain relief from morphine? Individual variation in sensitivity to morphine and the need to switch to an alternative opioid in cancer patients. Support Care Cancer 2006; 14: 5664.
  • 4
    Slatkin NE. Opioid switching and rotation in primary care: implementation and clinical utility. Curr Med Res Opin 2009; 25: 21332150.
  • 5
    Kasai S, Hayashida M, Sora I, Ikeda K. Candidate gene polymorphisms predicting individual sensitivity to opioids. Naunyn Schmiedebergs Arch Pharmacol 2008; 377: 269281.
  • 6
    Turk DC, Dworkin RH, Burke LB, Gershon R, Rothman M, Scott J, Allen RR, Atkinson JH, Chandler J, Cleeland C, Cowan P, Dimitrova R, Dionne R, Farrar JT, Haythornthwaite JA, Hertz S, Jadad AR, Jensen MP, Kellstein D, Kerns RD, Manning DC, Martin S, Max MB, McDermott MP, McGrath P, Moulin DE, Nurmikko T, Quessy S, Raja S, Rappaport BA, Rauschkolb C, Robinson JP, Royal MA, Simon L, Stauffer JW, Stucki G, Tollett J, von Stein T, Wallace MS, Wernicke J, White RE, Williams AC, Witter J, Wyrwich KW. Developing patient-reported outcome measures for pain clinical trials: IMMPACT recommendations. Pain 2006; 125: 208215.
  • 7
    Klepstad P, Rakvag TT, Kaasa S, Holthe M, Dale O, Borchgrevink PC, Baar C, Vikan T, Krokan HE, Skorpen F. The 118 A > G polymorphism in the human micro-opioid receptor gene may increase morphine requirements in patients with pain caused by malignant disease. Acta Anaesthesiol Scand 2004; 48: 12321239.
  • 8
    Rakvag TT, Klepstad P, Baar C, Kvam TM, Dale O, Kaasa S, Krokan HE, Skorpen F. The Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene may influence morphine requirements in cancer pain patients. Pain 2005; 116: 7378.
  • 9
    Galvan A, Skorpen F, Klepstad P, Knudsen AK, Fladvad T, Falvella FS, Pigni A, Brunelli C, Caraceni A, Kaasa S, Dragani TA. Multiple Loci modulate opioid therapy response for cancer pain. Clin Cancer Res 2011; 17: 45814587.
  • 10
    Romberg RR, Olofsen E, Bijl H, Taschner PE, Teppema LJ, Sarton EY, van Kleef SW, Dahan A. Polymorphism of mu-opioid receptor gene (OPRM1:c.118A>G) does not protect against opioid-induced respiratory depression despite reduced analgesic response. Anesthesiology 2005; 102: 522530.
  • 11
    Campa D, Gioia A, Tomei A, Poli P, Barale R. Association of ABCB1/MDR1 and OPRM1 gene polymorphisms with morphine pain relief. Clin Pharmacol Ther 2008; 83: 559566.
  • 12
    Landau R, Kern C, Columb MO, Smiley RM, Blouin JL. Genetic variability of the mu-opioid receptor influences intrathecal fentanyl analgesia requirements in laboring women. Pain 2008; 139: 514.
  • 13
    Chou WY, Yang LC, Lu HF, Ko JY, Wang CH, Lin SH, Lee TH, Concejero A, Hsu CJ. Association of mu-opioid receptor gene polymorphism (A118G) with variations in morphine consumption for analgesia after total knee arthroplasty. Acta Anaesthesiol Scand 2006; 50: 787792.
  • 14
    Chou WY, Wang CH, Liu PH, Liu CC, Tseng CC, Jawan B. Human opioid receptor A118G polymorphism affects intravenous patient-controlled analgesia morphine consumption after total abdominal hysterectomy. Anesthesiology 2006; 105: 334337.
  • 15
    Reyes-Gibby CC, Shete S, Rakvag T, Bhat SV, Skorpen F, Bruera E, Kaasa S, Klepstad P. Exploring joint effects of genes and the clinical efficacy of morphine for cancer pain: OPRM1 and COMT gene. Pain 2007; 130: 2530.
  • 16
    Klepstad P, Fladvad T, Skorpen F, Bjordal K, Caraceni A, Dale O, Davies A, Kloke M, Lundstrom S, Maltoni M, Radbruch L, Sabatowski R, Sigurdardottir V, Strasser F, Fayers PM, Kaasa S. Influence from genetic variability on opioid use for cancer pain: a European genetic association study of 2294 cancer pain patients. Pain May 2011; 152: 11391145.
  • 17
    Ross JR, Riley J, Taegetmeyer AB, Sato H, Gretton S, du Bois RM, Welsh KI. Genetic variation and response to morphine in cancer patients: catechol-o-methyltransferase and multidrug resistance-1 gene polymorphisms are associated with central side effects. Cancer March 15 2008; 112: 13901403.
  • 18
    Laugsand EA, Fladvad T, Skorpen F, Maltoni M, Kaasa S, Fayers P, Klepstad P. Clinical and genetic factors associated with nausea and vomiting in cancer patients receiving opioids. Eur J Cancer 2011; 47: 16821691.
  • 19
    Hjermstad MJ, Gibbins J, Haugen DF, Caraceni A, Loge JH, Kaasa S. Pain assessment tools in palliative care: an urgent need for consensus. Palliat Med 2008; 22: 895903.
  • 20
    Hjermstad MJ, Fainsinger R, Kaasa S. Assessment and classification of cancer pain. Curr Opin Support Palliat Care 2009; 3: 2430.
  • 21
    Knudsen AK, Brunelli C, Kaasa S, Apolone G, Corli O, Montanari M, Fainsinger R, Aass N, Fayers P, Caraceni A, Klepstad P. Which variables are associated with pain intensity and treatment response in advanced cancer patients? – Implications for a future classification system for cancer pain. Eur J Pain 2011; 15: 320327.
  • 22
    Chanock SJ, Manolio T, Boehnke M, Boerwinkle E, Hunter DJ, Thomas G, Hirschhorn JN, Abecasis G, Altshuler D, Bailey-Wilson JE, Brooks LD, Cardon LR, Daly M, Donnelly P, Fraumeni JF, Freimer NB, Gerhard DS, Gunter C, Guttmacher AE, Guyer MS, Harris EL, Hoh J, Hoover R, Kong CA, Merikangas KR, Morton CC, Palmer LJ, Phimister EG, Rice JP, Roberts J, Rotimi C, Tucker MA, Vogan KJ, Wacholder S, Wijsman EM, Winn DM, Collins FS. Replicating genotype-phenotype associations. Nature 2007; 447: 655660.
  • 23
    Neddermeyer TJ, Fluhr K, Lotsch J. Principle components analysis of pain thresholds to thermal, electrical, and mechanical stimuli suggests a predominant common source of variance. Pain 2008; 138: 286291.
  • 24
    Ger LP, Ho ST, Sun WZ, Wang MS, Cleeland CS. Validation of the Brief Pain Inventory in a Taiwanese population. J Pain Symptom Manage 1999; 18: 316322.
  • 25
    Fan G, Hadi S, Chow E. Symptom clusters in patients with advanced-stage cancer referred for palliative radiation therapy in an outpatient setting. Support Cancer Ther 2007; 4: 157162.
  • 26
    Skerman HM, Yates PM, Battistutta D. Multivariate methods to identify cancer-related symptom clusters. Res Nurs Health 2009; 32: 345360.
  • 27
    Chen E, Nguyen J, Khan L, Zhang L, Cramarossa G, Tsao M, Danjoux C, Barnes E, Sahgal A, Holden L, Jon F, Chow E. Symptom clusters in patients with advanced cancer: a reanalysis comparing different statistical methods. J Pain Symptom Manage 2012; 44: 2332.
  • 28
    Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singapore 1994; 23: 129138.
  • 29
    Rakvag TT, Ross JR, Sato H, Skorpen F, Kaasa S, Klepstad P. Genetic variation in the catechol-O-methyltransferase (COMT) gene and morphine requirements in cancer patients with pain. Mol Pain 2008; 4: 6475.
  • 30
    Mercadante S, Ferrera P, Villari P, Casuccio A, Intravaia G, Mangione S. Frequency, indications, outcomes, and predictive factors of opioid switching in an acute palliative care unit. J Pain Symptom Manage 2009; 37: 632641.
  • 31
    Salazar LA, Hirata MH, Cavalli SA, Machado MO, Hirata RD. Optimized procedure for DNA isolation from fresh and cryopreserved clotted human blood useful in clinical molecular testing. Clin Chem 1998; 44: (8 Pt 1): 17481750.
  • 32
    Bunce M, O'Neill CM, Barnardo M, Krausa P, Browning MJ, Morris PJ, Welsh KI. Phototyping: comprehensive DNA typing for HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 & DQB1 by PCR with 144 primer mixes utilising sequence-specific primers (PCR-SSP). Tissue Antigens 1995; 46: 355367.
  • 33
    Welsh K, Bunce M. Molecular typing for the MHC with PCR-SSP. Rev Immunogenet 1999; 1: 157176.
  • 34
    Kaiser HF. The application of electronic computers to factor analysis. Educ Psychol Meas 1960; 20: 141151.
  • 35
    Tabachnick BG, Fidell LS. Using Multivariate Statistics, 6th edn. Upper Saddle River, NJ: Pearson Education Inc, 2012; 620, 649.
  • 36
    Field A. Discovering Statistics Using SPSS, 2nd edn. London: SAGE Publishers LtD, 2005; 638, 642.
  • 37
    Mundform DJ, Perrett JJ, Schaffer J, Piccone A, Roozeboom M. Bonferroni adjustments in tests for regression coefficients. Multiple Linear Regression Viewpoints 2006; 32: 16.
  • 38
    Klepstad P, Loge JH, Borchgrevink PC, Mendoza TR, Cleeland CS, Kaasa S. The Norwegian brief pain inventory questionnaire: translation and validation in cancer pain patients. J Pain Symptom Manage 2002; 24: 517525.
  • 39
    Caraceni A, Mendoza TR, Mencaglia E, Baratella C, Edwards K, Forjaz MJ, Martini C, Serlin RC, De Conno F, Cleeland CS. A validation study of an Italian version of the brief pain inventory (Breve Questionario per la Valutazione del Dolore). Pain 1996; 65: 8792.
  • 40
    Raynor K, Kong H, Chen Y, Yasuda K, Yu L, Bell GI, Reisine T. Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors. Mol Pharmacol 1994; 45: 330334.
  • 41
    Satoh M, Minami M. Molecular pharmacology of the opioid receptors. Pharmacol Ther 1995; 68: 343364.
  • 42
    Khotib J, Narita M, Suzuki M, Yajima Y, Suzuki T. Functional interaction among opioid receptor types: up-regulation of mu- and delta-opioid receptor functions after repeated stimulation of kappa-opioid receptors. Neuropharmacology 2004; 46: 531540.
  • 43
    Rozenfeld R, bul-Husn NS, Gomez I, Devi LA. An emerging role for the delta opioid receptor in the regulation of mu opioid receptor function. ScientificWorldJournal 2007; 7: 6473.
  • 44
    Park PS, Palczewski K. Diversifying the repertoire of G protein-coupled receptors through oligomerization. Proc Natl Acad Sci U S A 2005; 102: 87938794.
  • 45
    Gomes I, Gupta A, Filipovska J, Szeto HH, Pintar JE, Devi LA. A role for heterodimerization of mu and delta opiate receptors in enhancing morphine analgesia. Proc Natl Acad Sci U S A 2004; 101: 51355139.
  • 46
    Decaillot FM, Rozenfeld R, Gupta A, Devi LA. Cell surface targeting of mu-delta opioid receptor heterodimers by RTP4. Proc Natl Acad Sci U S A 2008; 105: 1604516050.
  • 47
    Gomes I, Jordan BA, Gupta A, Trapaidze N, Nagy V, Devi LA. Heterodimerization of mu and delta opioid receptors: a role in opiate synergy. J Neurosci 2000; 20: RC110.
  • 48
    Lotsch J, Skarke C, Grosch S, Darimont J, Schmidt H, Geisslinger G. The polymorphism A118G of the human mu-opioid receptor gene decreases the pupil constrictory effect of morphine-6-glucuronide but not that of morphine. Pharmacogenetics 2002; 12: 39.
  • 49
    Janicki PK, Schuler G, Francis D, Bohr A, Gordin V, Jarzembowski T, Ruiz-Velasco V, Mets B. A genetic association study of the functional A118G polymorphism of the human mu-opioid receptor gene in patients with acute and chronic pain. Anesth Analg 2006; 103: 10111017.
  • 50
    Coulbault L, Beaussier M, Verstuyft C, Weickmans H, Dubert L, Tregouet D, Desco C, Parc Y, Lienhart A, Jaillon P, Becquemont L. Environmental and genetic factors associated with morphine response in the postoperative period. Clin Pharmacol Ther 2006; 79: 316324.
  • 51
    Bond C, LaForge KS, Tian M, Melia D, Zhang S, Borg L, Gong J, Schluger J, Strong JA, Leal SM, Tischfield JA, Kreek MJ, Yu L. Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci U S A 1998; 95: 96089613.
  • 52
    Kroslak T, LaForge KS, Gianotti RJ, Ho A, Nielsen DA, Kreek MJ. The single nucleotide polymorphism A118G alters functional properties of the human mu opioid receptor. J Neurochem 2007; 103: 7787.
  • 53
    Beyer A, Koch T, Schroder H, Schulz S, Hollt V. Effect of the A118G polymorphism on binding affinity, potency and agonist-mediated endocytosis, desensitization, and resensitization of the human mu-opioid receptor. J Neurochem 2004; 89: 553560.
  • 54
    Diatchenko L, Nackley AG, Tchivileva IE, Shabalina SA, Maixner W. Genetic architecture of human pain perception. Trends Genet 2007; 23: 605613.
  • 55
    Patt RB, Proper G, Reddy S. The neuroleptics as adjuvant analgesics. J Pain Symptom Manage 1994; 9: 446453.
  • 56
    Zhang J, He J, Chen YM, Wang JH, Ma YY. Morphine and propranolol co-administration impair consolidation of Y-maze spatial recognition memory. Brain Res 2008; 1230: 150157.
  • 57
    Cecchi M, Capriles N, Watson SJ, Akil H. Beta1 adrenergic receptors in the bed nucleus of stria terminalis mediate differential responses to opiate withdrawal. Neuropsychopharmacology 2007; 32: 589599.
  • 58
    Yu XC, Wang HX, Zhang WM, Wong TM. Cross-talk between cardiac kappa-opioid and beta-adrenergic receptors in developing hypertensive rats. J Mol Cell Cardiol 1999; 31: 597605.
  • 59
    Jordan BA, Trapaidze N, Gomes I, Nivarthi R, Devi LA. Oligomerization of opioid receptors with beta 2-adrenergic receptors: a role in trafficking and mitogen-activated protein kinase activation. Proc Natl Acad Sci U S A 2001; 98: 343348.
  • 60
    Shan J, Yu XC, Fung ML, Wong TM. Attenuated ‘cross talk’ between kappa-opioid receptors and beta-adrenoceptors in the heart of chronically hypoxic rats. Pflugers Arch 2002; 444: 126132.
  • 61
    Shabalina SA, Zaykin DV, Gris P, Ogurtsov AY, Gauthier J, Shibata K, Tchivileva IE, Belfer I, Mishra B, Kiselycznyk C, Wallace MR, Staud R, Spiridonov NA, Max MB, Goldman D, Fillingim RB, Maixner W, Diatchenko L. Expansion of the human {micro}-opioid receptor gene architecture: novel functional variants. Hum Mol Genet March 15 2009; 18: 10371051.
  • 62
    Dworkin BR, Filewich RJ, Miller NE, Craigmyle N, Pickering TG. Baroreceptor activation reduces reactivity to noxious stimulation: implications for hypertension. Science 1979; 205: 12991301.
  • 63
    McCubbin JA, Helfer SG, Switzer FS, III, Galloway C, Griffith WV. Opioid analgesia in persons at risk for hypertension. Psychosom Med 2006; 68: 116120.
  • 64
    Holthe M, Klepstad P, Zahlsen K, Borchgrevink PC, Hagen L, Dale O, Kaasa S, Krokan HE, Skorpen F. Morphine glucuronide-to-morphine plasma ratios are unaffected by the UGT2B7 H268Y and UGT1A1*28 polymorphisms in cancer patients on chronic morphine therapy. Eur J Clin Pharmacol 2002; 58: 353356.
  • 65
    Holthe M, Rakvag TN, Klepstad P, Idle JR, Kaasa S, Krokan HE, Skorpen F. Sequence variations in the UDP-glucuronosyltransferase 2B7 (UGT2B7) gene: identification of 10 novel single nucleotide polymorphisms (SNPs) and analysis of their relevance to morphine glucuronidation in cancer patients. Pharmacogenomics J 2003; 3: 1726.
  • 66
    Walters JT, Owen MJ. Endophenotypes in psychiatric genetics. Mol Psychiatry 2007; 12: 886890.
  • 67
    Roy K, Smith J, Kolsum U, Borrill Z, Vestbo J, Singh D. COPD phenotype description using principal components analysis. Respir Res 2009; 10: 4148.
  • 68
    Hirschhorn JN, Daly MJ. Genome-wide association studies for common diseases and complex traits. Nat Rev Genet 2005; 6: 95108.
  • 69
    Wang WY, Barratt BJ, Clayton DG, Todd JA. Genome-wide association studies: theoretical and practical concerns. Nat Rev Genet 2005; 6: 109118.