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Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Opioids | Research article

Opioid response in paediatric cancer patients and the Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene: an Italian study on 87 cancer children and a systematic review

Authors: Ersilia Lucenteforte, Alfredo Vannacci, Giada Crescioli, Niccolò Lombardi, Laura Vagnoli, Laura Giunti, Valentina Cetica, Maria Luisa Coniglio, Alessandra Pugi, Roberto Bonaiuti, Maurizio Aricò, Sabrina Giglio, Andrea Messeri, Roberto Barale, Lisa Giovannelli, Alessandro Mugelli, Valentina Maggini

Published in: BMC Cancer | Issue 1/2019

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Abstract

Background

Genetic polymorphisms in genes involved in pain modulation have been reported to be associated to opioid efficacy and safety in different clinical settings.

Methods

The association between COMT Val158Met polymorphism (rs4680) and the inter-individual differences in the response to opioid analgesic therapy was investigated in a cohort of 87 Italian paediatric patients receiving opioids for cancer pain (STOP Pain study). Furthermore, a systematic review of the association between opioid response in cancer patients and the COMT polymorphism was performed in accordance with the Cochrane Handbook and the Prisma Statement.

Results

In the 87 paediatric patients, pain intensity (total time needed to reach the lowest possible level) was significantly higher for G/G than A/G and A/A carriers (p-value = 0.042). In the 60 patients treated only with morphine, the mean of total dose to reach the same pain intensity was significantly higher for G/G than A/G and A/A carriers (p-value = 0.010). Systematic review identified five studies on adults, reporting that opioid dose (mg after 24 h of treatment from the first pain measurement) was higher for G/G compared to A/G and A/A carriers.

Conclusions

Present research suggests that the A allele in COMT polymorphism could be a marker of opioid sensitivity in paediatric cancer patients (STOP Pain), as well as in adults (Systematic Review), indicating that the polymorphism impact could be not age-dependent in the cancer pain context.

Trial registration

Registration number: CRD42017057831.
Appendix
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Literature
1.
go back to reference World Health Organization. Cancer Pain Relief – with a guide to opioid availability 1996. World Health Organization. Cancer Pain Relief – with a guide to opioid availability 1996.
2.
go back to reference World Health Organization. WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses 2012. World Health Organization. WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses 2012.
3.
go back to reference Droney J, Riley J, Ross JR. Evolving knowledge of opioid genetics in cancer pain. Clin Oncol. 2011;23(6):418–28.CrossRef Droney J, Riley J, Ross JR. Evolving knowledge of opioid genetics in cancer pain. Clin Oncol. 2011;23(6):418–28.CrossRef
4.
go back to reference Kapur BM, Lala PK, Shaw JL. Pharmacogenetics of chronic pain management. Clin Biochem. 2014;47(13–14):1169–87.PubMedCrossRef Kapur BM, Lala PK, Shaw JL. Pharmacogenetics of chronic pain management. Clin Biochem. 2014;47(13–14):1169–87.PubMedCrossRef
5.
go back to reference van Esch AA, de Vries E, Te Morsche RH, van Oijen MG, Jansen JB, Drenth JP. Catechol-O-methyltransferase (COMT) gene variants and pain in chronic pancreatitis. Neth J Med. 2011;69(7):330–4.PubMed van Esch AA, de Vries E, Te Morsche RH, van Oijen MG, Jansen JB, Drenth JP. Catechol-O-methyltransferase (COMT) gene variants and pain in chronic pancreatitis. Neth J Med. 2011;69(7):330–4.PubMed
6.
go back to reference Berthele A, Platzer S, Jochim B, Boecker H, Buettner A, Conrad B, Riemenschneider M, Toelle TR. COMT Val108/158Met genotype affects the mu-opioid receptor system in the human brain: evidence from ligand-binding, G-protein activation and preproenkephalin mRNA expression. NeuroImage. 2005;28(1):185–93.PubMedCrossRef Berthele A, Platzer S, Jochim B, Boecker H, Buettner A, Conrad B, Riemenschneider M, Toelle TR. COMT Val108/158Met genotype affects the mu-opioid receptor system in the human brain: evidence from ligand-binding, G-protein activation and preproenkephalin mRNA expression. NeuroImage. 2005;28(1):185–93.PubMedCrossRef
7.
go back to reference Moskovitz J, Walss-Bass C, Cruz DA, Thompson PM, Hairston J, Bortolato M. The enzymatic activities of brain catechol-O-methyltransferase (COMT) and methionine sulphoxide reductase are correlated in a COMT Val/met allele-dependent fashion. Neuropathol Appl Neurobiol. 2015;41(7):941–51.PubMedPubMedCentralCrossRef Moskovitz J, Walss-Bass C, Cruz DA, Thompson PM, Hairston J, Bortolato M. The enzymatic activities of brain catechol-O-methyltransferase (COMT) and methionine sulphoxide reductase are correlated in a COMT Val/met allele-dependent fashion. Neuropathol Appl Neurobiol. 2015;41(7):941–51.PubMedPubMedCentralCrossRef
8.
go back to reference Smith SB, Reenilä I, Männistö PT, Slade GD, Maixner W, Diatchenko L, Nackley AG. Epistasis between polymorphisms in COMT, ESR1, and GCH1 influences COMT enzyme activity and pain. Pain. 2014;155(11):2390–9.PubMedPubMedCentralCrossRef Smith SB, Reenilä I, Männistö PT, Slade GD, Maixner W, Diatchenko L, Nackley AG. Epistasis between polymorphisms in COMT, ESR1, and GCH1 influences COMT enzyme activity and pain. Pain. 2014;155(11):2390–9.PubMedPubMedCentralCrossRef
9.
go back to reference Zubieta JK, Heitzeg MM, Smith YR, Bueller JA, Xu K, Xu Y, Koeppe RA, Stohler CS, Goldman D. COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science. 2003;299(5610):1240–3.PubMedCrossRef Zubieta JK, Heitzeg MM, Smith YR, Bueller JA, Xu K, Xu Y, Koeppe RA, Stohler CS, Goldman D. COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science. 2003;299(5610):1240–3.PubMedCrossRef
10.
go back to reference Kurita GP, Ekholm O, Kaasa S, Klepstad P, Skorpen F, Sjogren P. Genetic variation and cognitive dysfunction in opioid-treated patients with cancer. Brain behav. 2016;6(7):e00471.PubMedPubMedCentralCrossRef Kurita GP, Ekholm O, Kaasa S, Klepstad P, Skorpen F, Sjogren P. Genetic variation and cognitive dysfunction in opioid-treated patients with cancer. Brain behav. 2016;6(7):e00471.PubMedPubMedCentralCrossRef
11.
go back to reference World Health Organization. GLOBOCAN-estimated cancer incidence, Mortality and prevalence worldwide 2012. World Health Organization. GLOBOCAN-estimated cancer incidence, Mortality and prevalence worldwide 2012.
12.
go back to reference Mirabello L, Troisi RJ, Savage SA. International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons. Int J Cancer. 2009;125(1):229–34.PubMedPubMedCentralCrossRef Mirabello L, Troisi RJ, Savage SA. International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons. Int J Cancer. 2009;125(1):229–34.PubMedPubMedCentralCrossRef
13.
go back to reference Lucenteforte E, Vagnoli L, Pugi A, Crescioli G, Lombardi N, Bonaiuti R, Aricò M, Giglio S, Messeri A, Mugelli A, et al. A systematic review of the risk factors for clinical response to opioids for all-age patients with cancer-related pain and presentation of the paediatric STOP pain study. BMC Cancer. 2018;18(1):568.PubMedPubMedCentralCrossRef Lucenteforte E, Vagnoli L, Pugi A, Crescioli G, Lombardi N, Bonaiuti R, Aricò M, Giglio S, Messeri A, Mugelli A, et al. A systematic review of the risk factors for clinical response to opioids for all-age patients with cancer-related pain and presentation of the paediatric STOP pain study. BMC Cancer. 2018;18(1):568.PubMedPubMedCentralCrossRef
17.
go back to reference Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA, Abecasis GR, et al. The 1000 genomes project consortium. A global reference for human genetic variation. Nature. 2015;526(7571):68–74.PubMedCrossRef Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA, Abecasis GR, et al. The 1000 genomes project consortium. A global reference for human genetic variation. Nature. 2015;526(7571):68–74.PubMedCrossRef
18.
go back to reference Klepstad P, Fladvad T, Skorpen F, Bjordal K, Caraceni A, Dale O, Davies A, Kloke M, Lundstrom S, Maltoni M, et al. 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.PubMedCrossRef Klepstad P, Fladvad T, Skorpen F, Bjordal K, Caraceni A, Dale O, Davies A, Kloke M, Lundstrom S, Maltoni M, et al. 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.PubMedCrossRef
19.
go back to reference Barratt DT, Bandak B, Klepstad P, Dale O, Kaasa S, Christrup LL, Tuke J, Somogyi AA. Genetic, pathological and physiological determinants of transdermal fentanyl pharmacokinetics in 620 cancer patients of the EPOS study. Pharmacogenet Genomics. 2014;24(4):185–94.PubMedCrossRef Barratt DT, Bandak B, Klepstad P, Dale O, Kaasa S, Christrup LL, Tuke J, Somogyi AA. Genetic, pathological and physiological determinants of transdermal fentanyl pharmacokinetics in 620 cancer patients of the EPOS study. Pharmacogenet Genomics. 2014;24(4):185–94.PubMedCrossRef
20.
go back to reference Barratt DT, Klepstad P, Dale O, Kaasa S, Somogyi AA. Innate immune Signalling genetics of Pain, cognitive dysfunction and sickness symptoms in Cancer Pain patients treated with transdermal fentanyl. PLoS One. 2015;10(9):e0137179.PubMedPubMedCentralCrossRef Barratt DT, Klepstad P, Dale O, Kaasa S, Somogyi AA. Innate immune Signalling genetics of Pain, cognitive dysfunction and sickness symptoms in Cancer Pain patients treated with transdermal fentanyl. PLoS One. 2015;10(9):e0137179.PubMedPubMedCentralCrossRef
21.
go back to reference 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(11):1682–91.PubMedCrossRef 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(11):1682–91.PubMedCrossRef
22.
go back to reference Matsuoka H, Arao T, Makimura C, Takeda M, Kiyota H, Tsurutani J, Fujita Y, Matsumoto K, Kimura H, Otsuka M, et al. Expression changes in arrestin beta 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.PubMed Matsuoka H, Arao T, Makimura C, Takeda M, Kiyota H, Tsurutani J, Fujita Y, Matsumoto K, Kimura H, Otsuka M, et al. Expression changes in arrestin beta 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.PubMed
23.
go back to reference 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(1–2):73–8.PubMedCrossRef 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(1–2):73–8.PubMedCrossRef
24.
go back to reference 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;4:64.PubMedPubMedCentralCrossRef 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;4:64.PubMedPubMedCentralCrossRef
25.
go back to reference Ross JR, Rutter D, Welsh K, Joel SP, Goller K, Wells AU, Du Bois R, Riley J. Clinical response to morphine in cancer patients and genetic variation in candidate genes. Pharmacogenomics J. 2005;5(5):324–36.PubMedCrossRef Ross JR, Rutter D, Welsh K, Joel SP, Goller K, Wells AU, Du Bois R, Riley J. Clinical response to morphine in cancer patients and genetic variation in candidate genes. Pharmacogenomics J. 2005;5(5):324–36.PubMedCrossRef
26.
go back to reference Chatti I, Creveaux I, Woillard JB, Langlais S, Amara A, Ben Fatma L, Saad A, Gribaa M, Libert F. Association of the OPRM1 and COMT genes' polymorphisms with the efficacy of morphine in Tunisian cancer patients: impact of the high genetic heterogeneity in Tunisia? Therapie. 2016;71(5):507–13.PubMedCrossRef Chatti I, Creveaux I, Woillard JB, Langlais S, Amara A, Ben Fatma L, Saad A, Gribaa M, Libert F. Association of the OPRM1 and COMT genes' polymorphisms with the efficacy of morphine in Tunisian cancer patients: impact of the high genetic heterogeneity in Tunisia? Therapie. 2016;71(5):507–13.PubMedCrossRef
27.
go back to reference 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(1–2):25–30.PubMedCrossRef 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(1–2):25–30.PubMedCrossRef
28.
go back to reference 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. 2008;112(6):1390–403.PubMedCrossRef 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. 2008;112(6):1390–403.PubMedCrossRef
29.
go back to reference Tammimaki A, Mannisto PT. Catechol-O-methyltransferase gene polymorphism and chronic human pain: a systematic review and meta-analysis. Pharmacogenet Genomics. 2012;22(9):673–91.PubMedCrossRef Tammimaki A, Mannisto PT. Catechol-O-methyltransferase gene polymorphism and chronic human pain: a systematic review and meta-analysis. Pharmacogenet Genomics. 2012;22(9):673–91.PubMedCrossRef
30.
31.
go back to reference Chau CM, Ranger M, Sulistyoningrum D, Devlin AM, Oberlander TF, Grunau RE. Neonatal pain and COMT Val158Met genotype in relation to serotonin transporter (SLC6A4) promoter methylation in very preterm children at school age. Front Behav Neurosci. 2014;8:409.PubMedPubMedCentralCrossRef Chau CM, Ranger M, Sulistyoningrum D, Devlin AM, Oberlander TF, Grunau RE. Neonatal pain and COMT Val158Met genotype in relation to serotonin transporter (SLC6A4) promoter methylation in very preterm children at school age. Front Behav Neurosci. 2014;8:409.PubMedPubMedCentralCrossRef
32.
go back to reference Elens L, Norman E, Matic M, Rane A, Fellman V, van Schaik RH. Genetic predisposition to poor opioid response in preterm infants: impact of KCNJ6 and COMT polymorphisms on Pain relief after endotracheal intubation. Ther Drug Monit. 2016;38(4):525–33.PubMedCrossRef Elens L, Norman E, Matic M, Rane A, Fellman V, van Schaik RH. Genetic predisposition to poor opioid response in preterm infants: impact of KCNJ6 and COMT polymorphisms on Pain relief after endotracheal intubation. Ther Drug Monit. 2016;38(4):525–33.PubMedCrossRef
33.
go back to reference Mamie C, Rebsamen MC, Morris MA, Morabia A. First evidence of a polygenic susceptibility to pain in a pediatric cohort. Anesth Analg. 2013;116(1):170–7.PubMedCrossRef Mamie C, Rebsamen MC, Morris MA, Morabia A. First evidence of a polygenic susceptibility to pain in a pediatric cohort. Anesth Analg. 2013;116(1):170–7.PubMedCrossRef
34.
go back to reference Matic M, Simons SH, van Lingen RA, van Rosmalen J, Elens L, de Wildt SN, Tibboel D, van Schaik RH. Rescue morphine in mechanically ventilated newborns associated with combined OPRM1 and COMT genotype. Pharmacogenomics. 2014;15(10):1287–95.PubMedCrossRef Matic M, Simons SH, van Lingen RA, van Rosmalen J, Elens L, de Wildt SN, Tibboel D, van Schaik RH. Rescue morphine in mechanically ventilated newborns associated with combined OPRM1 and COMT genotype. Pharmacogenomics. 2014;15(10):1287–95.PubMedCrossRef
35.
go back to reference van Meurs JB, Uitterlinden AG, Stolk L, Kerkhof HJ, Hofman A, Pols HA, Bierma-Zeinstra SM. A functional polymorphism in the catechol-O-methyltransferase gene is associated with osteoarthritis-related pain. Arthritis Rheum. 2009;60(2):628–9.PubMedCrossRef van Meurs JB, Uitterlinden AG, Stolk L, Kerkhof HJ, Hofman A, Pols HA, Bierma-Zeinstra SM. A functional polymorphism in the catechol-O-methyltransferase gene is associated with osteoarthritis-related pain. Arthritis Rheum. 2009;60(2):628–9.PubMedCrossRef
36.
go back to reference Diatchenko L, Slade GD, Nackley AG, Bhalang K, Sigurdsson A, Belfer I, Goldman D, Xu K, Shabalina SA, Shagin D, et al. Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet. 2005;14(1):135–43.PubMedCrossRef Diatchenko L, Slade GD, Nackley AG, Bhalang K, Sigurdsson A, Belfer I, Goldman D, Xu K, Shabalina SA, Shagin D, et al. Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet. 2005;14(1):135–43.PubMedCrossRef
37.
go back to reference Hunt A, Joel S, Dick G, Goldman A. Population pharmacokinetics of oral morphine and its glucuronides in children receiving morphine as immediate-release liquid or sustained-release tablets for cancer pain. J Pediatr. 1999;135(1):47–55.PubMedCrossRef Hunt A, Joel S, Dick G, Goldman A. Population pharmacokinetics of oral morphine and its glucuronides in children receiving morphine as immediate-release liquid or sustained-release tablets for cancer pain. J Pediatr. 1999;135(1):47–55.PubMedCrossRef
38.
39.
go back to reference Lasky T, Ernst FR, Greenspan J, Wang S, Gonzalez L. Estimating pediatric inpatient medication use in the United States. Pharmacoepidemiol Drug Saf. 2011;20(1):76–82.PubMedCrossRef Lasky T, Ernst FR, Greenspan J, Wang S, Gonzalez L. Estimating pediatric inpatient medication use in the United States. Pharmacoepidemiol Drug Saf. 2011;20(1):76–82.PubMedCrossRef
40.
go back to reference Friedrichsdorf SJ, Postier A, Eull D, Weidner C, Foster L, Gilbert M, Campbell F. Pain outcomes in a US Children's hospital: a prospective cross-sectional survey. Hospital pediatrics. 2015;5(1):18–26.PubMedCrossRef Friedrichsdorf SJ, Postier A, Eull D, Weidner C, Foster L, Gilbert M, Campbell F. Pain outcomes in a US Children's hospital: a prospective cross-sectional survey. Hospital pediatrics. 2015;5(1):18–26.PubMedCrossRef
41.
go back to reference Dale O, Moksnes K, Kaasa S. European palliative care research collaborative pain guidelines: opioid switching to improve analgesia or reduce side effects. A systematic review. Palliat Med. 2011;25(5):494–503.PubMedCrossRef Dale O, Moksnes K, Kaasa S. European palliative care research collaborative pain guidelines: opioid switching to improve analgesia or reduce side effects. A systematic review. Palliat Med. 2011;25(5):494–503.PubMedCrossRef
42.
go back to reference Drewes AM, Jensen RD, Nielsen LM, Droney J, Christrup LL, Arendt-Nielsen L, Riley J, Dahan A. Differences between opioids: pharmacological, experimental, clinical and economical perspectives. Br J Clin Pharmacol. 2013;75(1):60–78.PubMedCrossRef Drewes AM, Jensen RD, Nielsen LM, Droney J, Christrup LL, Arendt-Nielsen L, Riley J, Dahan A. Differences between opioids: pharmacological, experimental, clinical and economical perspectives. Br J Clin Pharmacol. 2013;75(1):60–78.PubMedCrossRef
43.
go back to reference Shaheen PE, Walsh D, Lasheen W, Davis MP, Lagman RL. Opioid equianalgesic tables: are they all equally dangerous? J Pain Symptom Manag. 2009;38(3):409–17.CrossRef Shaheen PE, Walsh D, Lasheen W, Davis MP, Lagman RL. Opioid equianalgesic tables: are they all equally dangerous? J Pain Symptom Manag. 2009;38(3):409–17.CrossRef
44.
go back to reference Rabbitts JA, Palermo TM, Zhou C, Mangione-Smith R. Pain and Health-related quality of life after pediatric inpatient surgery. J Pain. 2015;16(12):1334–41.PubMedPubMedCentralCrossRef Rabbitts JA, Palermo TM, Zhou C, Mangione-Smith R. Pain and Health-related quality of life after pediatric inpatient surgery. J Pain. 2015;16(12):1334–41.PubMedPubMedCentralCrossRef
45.
go back to reference Voepel-Lewis T, Zanotti J, Dammeyer JA, Merkel S. Reliability and validity of the face, legs, activity, cry, consolability behavioral tool in assessing acute pain in critically ill patients. Am J Crit Care. 2010;19(1):55–61 quiz 62.PubMedCrossRef Voepel-Lewis T, Zanotti J, Dammeyer JA, Merkel S. Reliability and validity of the face, legs, activity, cry, consolability behavioral tool in assessing acute pain in critically ill patients. Am J Crit Care. 2010;19(1):55–61 quiz 62.PubMedCrossRef
46.
go back to reference Garra G, Singer AJ, Taira BR, Chohan J, Cardoz H, Chisena E, Thode HC Jr. Validation of the Wong-Baker FACES Pain rating scale in pediatric emergency department patients. Acad Emerg Med Off J Soc Acad Emerg Med. 2010;17(1):50–4.CrossRef Garra G, Singer AJ, Taira BR, Chohan J, Cardoz H, Chisena E, Thode HC Jr. Validation of the Wong-Baker FACES Pain rating scale in pediatric emergency department patients. Acad Emerg Med Off J Soc Acad Emerg Med. 2010;17(1):50–4.CrossRef
Metadata
Title
Opioid response in paediatric cancer patients and the Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene: an Italian study on 87 cancer children and a systematic review
Authors
Ersilia Lucenteforte
Alfredo Vannacci
Giada Crescioli
Niccolò Lombardi
Laura Vagnoli
Laura Giunti
Valentina Cetica
Maria Luisa Coniglio
Alessandra Pugi
Roberto Bonaiuti
Maurizio Aricò
Sabrina Giglio
Andrea Messeri
Roberto Barale
Lisa Giovannelli
Alessandro Mugelli
Valentina Maggini
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-5310-4

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