An Italian Twin Study of Non-Cancer Chronic Pain as a Wide Phenotype and Its Intensity
Abstract
:1. Introduction
2. Materials and Methods
2.1. Recruitment of Study Sample
2.2. Measures
2.2.1. Zygosity Assessment
2.2.2. CP Assessment
2.3. Statistical Analyses
2.3.1. Sample Description
2.3.2. Biometrical Structural Equation Modelling
3. Results
3.1. Participants
3.2. Sample Description
3.3. Biometrical Structural Equation Modelling
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AIC | Akaike information criterion |
COMT | Catechol-O-methyltransferase |
CP | Chronic pain |
CRHBP | Corticotropin-releasing hormone binding protein |
DZ | Dizygotic |
FKBP5 | FK506 binding protein 51 |
GCH1 | Guanosine-5-triphosphate cyclohydrolase 1 |
ESR1 | Estrogen receptor 1 |
HPA | Hypothalamic-pituitary-adrenal |
IASP | International Association for the Study of Pain |
ICD-11 | International Classification of Diseases-11 |
ITR | Italian Twin Registry |
MZ | Monozygotic |
NRS | Numerical rating scale |
OPRM1 | Opioid receptor mu 1 |
SNP | Single-nucleotide polymorphism |
VAS | Visual analogue scale |
References
- Treede, R.-D.; Rief, W.; Barke, A.; Aziz, Q.; Bennett, M.I.; Benoliel, R.; Cohen, M.; Evers, S.; Finnerup, N.B.; First, M.B.; et al. A classification of chronic pain for ICD-11. Pain 2015, 156, 1003–1007. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Breivik, H.; Collett, B.; Ventafridda, V.; Cohen, R.; Gallacher, D. Survey of chronic pain in Europe: Prevalence, impact on daily life, and treatment. Eur. J. Pain 2006, 10, 287–333. [Google Scholar] [CrossRef] [PubMed]
- Dahlhamer, J.; Lucas, J.; Zelaya, C.; Nahin, R.; Mackey, S.; DeBar, L.; Kerns, R.; Von Korff, M.; Porter, L.; Helmick, C. Prevalence of Chronic Pain and High-Impact Chronic Pain Among Adults-United States, 2016. MMWR Morb. Mortal. Wkly. Rep. 2018, 67, 1001–1006. [Google Scholar] [CrossRef] [PubMed]
- Niv, D.; Devor, M. Chronic pain as a disease in its own right. Pain Pract. 2004, 4, 179–181. [Google Scholar] [CrossRef] [PubMed]
- Breivik, H.; Eisenberg, E.; O’Brien, T. OPENMinds. The individual and societal burden of chronic pain in Europe: The case for strategic prioritisation and action to improve knowledge and availability of appropriate care. BMC Public Health 2013, 13, 1229. [Google Scholar] [CrossRef] [Green Version]
- Raffaeli, W.; Arnaudo, E. Pain as a disease: An overview. J. Pain Res. 2017, 10, 2003–2008. [Google Scholar] [CrossRef] [Green Version]
- Bevers, K.; Watts, L.; Kishino, N.D.; Gatchel, R.J. The biopsychosocial model of the assessment, prevention, and treatment of chronic pain. US Neurol. 2016, 12, 98–104. [Google Scholar] [CrossRef]
- Neale, M.C.; Cardon, L.R. Methodology for Genetic Studies of Twins and Families; Kluwer Academic Publishers: Dordrecht, The Netherlands, 1992. [Google Scholar]
- Nielsen, C.S.; Knudsen, G.P.; Steingrímsdóttir, Ó.A. Twin studies of pain. Clin. Genet. 2012, 82, 331–340. [Google Scholar] [CrossRef] [Green Version]
- Treede, R.D.; Rief, W.; Barke, A.; Aziz, Q.; Bennett, M.I.; Benoliel, R.; Cohen, M.; Evers, S.; Finnerup, N.B.; First, M.B.; et al. Chronic pain as a symptom or a disease: The IASP Classification of Chronic Pain for the International Classification of Diseases (ICD-11). Pain 2019, 160, 19–27. [Google Scholar] [CrossRef] [Green Version]
- Vehof, J.; Zavos, H.M.S.; Lachance, G.; Hammond, C.J.; Williams, F.M.K. Shared genetic factors underlie chronic pain syndromes. Pain 2014, 155, 1562–1568. [Google Scholar] [CrossRef]
- Steingrímsdóttir, Ó.A.; Landmark, T.; Macfarlane, G.J.; Nielsen, C.S. Defining chronic pain in epidemiological studies: A systematic review and meta-Analysis. Pain 2017, 158, 2092–2107. [Google Scholar] [CrossRef] [PubMed]
- Stazi, M.A.; Cotichini, R.; Patriarca, V.; Brescianini, S.; Fagnani, C.; D’Ippolito, C.; Cannoni, S.; Ristori, G.; Salvetti, M. The Italian Twin Project: From the personal identification number to a national twin registry. Twin Res. 2002, 5, 382–386. [Google Scholar] [CrossRef] [PubMed]
- Medda, E.; Toccaceli, V.; Fagnani, C.; Nisticò, L.; Brescianini, S.; Salemi, M.; Ferri, M.; D’Ippolito, C.; Alviti, S.; Arnofi, A.; et al. The Italian Twin Registry: An Update at 18 Years From Its Inception. Twin Res. Hum. Genet. 2019, 22, 572–578. [Google Scholar] [CrossRef] [Green Version]
- Medda, E.; Toccaceli, V.; Gigantesco, A.; Picardi, A.; Fagnani, C.; Stazi, M.A. The COVID-19 pandemic in Italy: Depressive symptoms immediately before and after the first lockdown. J. Affect. Disord. 2022, 298, 202–208. [Google Scholar] [CrossRef] [PubMed]
- Kyvik, K.O.; Green, A.; Beck-Nielsen, H. The new Danish Twin Register: Establishment and analysis of twinning rates. Int. J. Epidemiol. 1995, 24, 589–596. [Google Scholar] [CrossRef]
- Toccaceli, V.; Tenti, M.; Stazi, M.A.; Fagnani, C.; Medda, E.; Gargiulo, L.; Burgio, A.; Sampaolo, L.; Ferri, M.; Raffaeli, W. Development and Validation of the Italian “Brief Five-Item Chronic Pain Questionnaire” for Epidemiological Studies. J. Pain Res. 2022, 15, 1897–1913. [Google Scholar] [CrossRef]
- Medland, S.E.; Neale, M.C.; Eaves, L.J.; Neale, B.M. A note on the parameterization of Purcell’s G x E model for ordinal and binary data. Behav. Genet. 2009, 39, 220–229. [Google Scholar] [CrossRef]
- Neale, M.C.; Boker, S.M.; Xie, G.; Maes, H.H. Mx: Statistical Modeling, 7th ed.; Department of Psychiatry, Virginia Commonwealth University: Richmond, VA, USA, 2006. [Google Scholar]
- Raffaeli, W.; Tenti, M.; Corraro, A.; Malafoglia, V.; Ilari, S.; Balzani, E.; Bonci, A. Chronic Pain: What Does It Mean? A Review on the Use of the Term Chronic Pain in Clinical Practice. J. Pain Res. 2021, 14, 827–835. [Google Scholar] [CrossRef] [PubMed]
- Burri, A.; Ogata, S.; Rice, D.; Williams, F.M.K. Twelve-year follow-up of chronic pain in twins: Changes in environmental and genetic influence over time. Eur. J. Pain 2018, 22, 1439–1447. [Google Scholar] [CrossRef]
- Zorina-Lichtenwalter, K.; Meloto, C.B.; Khoury, S.; Diatchenko, L. Genetic predictors of human chronic pain conditions. Neuroscience 2016, 338, 36–62. [Google Scholar] [CrossRef]
- Williams, F.M.; Spector, T.D.; MacGregor, A.J. Pain reporting at different body sites is explained by a single underlying genetic factor. Rheumatology 2010, 49, 1753–1755. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tsepilov, Y.A.; Freidin, M.B.; Shadrina, A.S.; Sharapov, S.Z.; Elgaeva, E.E.; Zundert, J.V.; Karssen, L.C.; Suri, P.; Williams, F.M.K.; Aulchenko, Y.S. Analysis of genetically independent phenotypes identifies shared genetic factors associated with chronic musculoskeletal pain conditions. Commun. Biol. 2020, 3, 329. [Google Scholar] [CrossRef] [PubMed]
- Meng, W.; Adams, M.J.; Reel, P.; Rajendrakumar, A.; Huang, Y.; Deary, I.J.; Palmer, C.N.A.; McIntosh, A.M.; Smith, B.H. Genetic correlations between pain phenotypes and depression and neuroticism. Eur. J. Hum. Genet. 2020, 28, 358–366. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Eaves, L.J. Dominance alone is not enough. Behav. Genet. 1988, 18, 27–33. [Google Scholar] [CrossRef] [PubMed]
- Smith, S.B.; Reenilä, I.; Männistö, P.T.; Slade, G.D.; Maixner, W.; Diatchenko, L.; Nackley, A.G. Epistasis between polymorphisms in COMT, ESR1, and GCH1 influences COMT enzyme activity and pain. Pain 2014, 155, 2390–2399. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Linnstaedt, S.D.; Bortsov, A.V.; Soward, A.C.; Swor, R.; Peak, D.A.; Jones, J.; Rathlev, N.; Lee, D.C.; Domeier, R.; Hendry, P.L.; et al. CRHBP polymorphisms predict chronic pain development following motor vehicle collision. Pain 2016, 157, 273–279. [Google Scholar] [CrossRef] [Green Version]
- Khalil, H.; Sereika, S.M.; Dai, F.; Alexander, S.; Conley, Y.; Gruen, G.; Meng, L.; Siska, P.; Tarkin, I.; Henker, R. OPRM1 and COMT Gene-Gene Interaction Is Associated With Postoperative Pain and Opioid Consumption After Orthopedic Trauma. Biol. Res. Nurs. 2017, 19, 170–179. [Google Scholar] [CrossRef] [Green Version]
- Gatchel, R.J.; Reuben, D.B.; Dagenais, S.; Turk, D.C.; Chou, R.; Hershey, A.D.; Hicks, G.E.; Licciardone, J.C.; Horn, S.D. Research Agenda for the Prevention of Pain and Its Impact: Report of the Work Group on the Prevention of Acute and Chronic Pain of the Federal Pain Research Strategy. J. Pain 2018, 19, 837–851. [Google Scholar] [CrossRef] [Green Version]
- Burton, A.K.; Balagué, F.; Cardon, G.; Eriksen, H.R.; Henrotin, Y.; Lahad, A.; Leclerc, A.; Müller, G.; van der Beek, A.J. Chapter 2 European guidelines for prevention in low back pain: November 2004. Eur. Spine. J. 2006, 15 (Suppl. S2), S136–S168. [Google Scholar] [CrossRef] [Green Version]
- Fisher, E.; Eccleston, C. Psychological aspects of pain prevention. Pain Rep. 2021, 6, e926. [Google Scholar] [CrossRef]
Characteristics | Descriptive Estimates |
---|---|
N twins (N intact pairs) | 1524 (762) |
Age (mean (SD); range) | 39.2 (15.1); 18–82 |
Sex (% males) | 33.7% (N = 514) |
Zygosity | |
MZM | 18.0% (N = 274) |
MZF | 39.1% (N = 596) |
DZM | 7.9% (N = 120) |
DZF | 18.9% (N = 288) |
DZMF | 15.2% (N = 232) |
UZ | 0.9% (N = 14) |
Education (N = 1514) | |
Primary/Secondary school | 5.0% (N = 76) |
High school | 38.8% (N = 588) |
Professional school | 4.2% (N = 63) |
Three-year university degree | 14.7% (N = 223) |
Five-year university degree | 27.6% (N = 418) |
Post-graduate specialization | 9.6% (N = 146) |
CP occurrence (Yes/No, N = 1517) | 24.1% (N = 365) |
CP intensity (N = 361) | |
Very mild | 3.6% (N = 13) |
Mild | 18.3% (N = 66) |
Moderate | 60.4% (N = 218) |
Severe | 16.1% (N = 58) |
Very severe | 1.7% (N = 6) |
CP origin (N = 332) | |
Surgery | 2.7% (N = 9) |
Trauma without surgery | 39.8% (N = 132) |
Tumor diagnosed by a doctor | 1.5% (N = 5) |
Another illness diagnosed by a doctor | 35.2% (N = 117) |
Poorly defined disease | 20.8% (N = 69) |
CP treatment (Yes/No, N = 362) | 74.0% (N = 268) |
Benefits of treatment (Yes/No, N = 267) | 85.8% (N = 229) |
CP Occurrence | ||||
---|---|---|---|---|
Correlation | ||||
MZ (N = 430) | 0.37 (0.20, 0.52) | |||
DZ (N = 314) | −0.004 (−0.22, 0.22) | |||
MZM (N = 135) | 0.28 (−0.05, 0.57) | |||
DZM (N = 60) | −0.21 (−0.57, 0.23) | |||
MZF (N = 295) | 0.40 (0.21, 0.57) | |||
DZF (N = 139) | −0.06 (−0.39, 0.28) | |||
DZMF (N = 115) | 0.22 (−0.16, 0.56) | |||
Two-group (MZ, DZ) model-fitting analysis | ||||
Model | −2LL | Df | AIC | |
ADE | 1529.274 | 1488 | −1446.726 | |
ACE | 1531.033 | 1488 | −1444.967 | |
Proportions of variance | ||||
A | D | A + D | E | |
0 (0, 0.43) | 0.36 (0, 0.51) | 0.36 (0.19, 0.51) | 0.64 (0.49, 0.81) | |
Five-group (zygosity and sex) model-fitting analysis | ||||
Model | −2LL | Df | AIC | |
ADE | 1528.668 | 1485 | −1441.332 | |
ACE | 1530.229 | 1485 | −1439.771 | |
Proportions of variance | ||||
A | D | A + D | E | |
Males | 0 (0, 0.46) | 0.26 (0, 0.54) | 0.26 (0, 0.54) | 0.74 (0.46, 1) |
Females | 0 (0, 0.51) | 0.39 (0, 0.56) | 0.39 (0.20, 0.56) | 0.61 (0.44, 0.80) |
CP Intensity | ||||
Correlation | ||||
MZ (N = 427) | 0.31 (0.16, 0.44) | |||
DZ (N = 314) | 0.08 (−0.12, 0.28) | |||
MZM (N = 135) | 0.18 (−0.09, 0.44) | |||
DZM (N = 60) | −0.07 (−0.44, 0.35) | |||
MZF (N = 292) | 0.36 (0.18, 0.52) | |||
DZF (N = 139) | −0.07 (−0.37, 0.25) | |||
DZMF (N = 115) | 0.34 (0.01, 0.60) | |||
Two-group (MZ, DZ) model-fitting analysis | ||||
Model | −2LL | Df | AIC | |
ADE | 2166.933 | 1478 | −789.067 | |
ACE | 2167.348 | 1478 | −788.652 | |
Proportions of variance | ||||
A | D | A + D | E | |
0.02 (0, 0.42) | 0.29 (0, 0.44) | 0.31 (0.16, 0.44) | 0.69 (0.56, 0.84) | |
Five-group (zygosity and sex) model-fitting analysis | ||||
Model | −2LL | Df | AIC | |
ADE | 2166.666 | 1479 | −791.334 | |
ACE | 2167.161 | 1479 | −790.839 | |
Proportions of variance | ||||
A | D | A + D | E | |
Males | 0.03 (0, 0.43) | 0.18 (0, 0.46) | 0.21 (0, 0.46) | 0.79 (0.54, 1) |
Females | 0.03 (0, 0.47) | 0.31 (0, 0.50) | 0.34 (0.17, 0.50) | 0.66 (0.50, 0.83) |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Fagnani, C.; Toccaceli, V.; Tenti, M.; Medda, E.; Ferri, M.; Stazi, M.A.; Raffaeli, W. An Italian Twin Study of Non-Cancer Chronic Pain as a Wide Phenotype and Its Intensity. Medicina 2022, 58, 1522. https://doi.org/10.3390/medicina58111522
Fagnani C, Toccaceli V, Tenti M, Medda E, Ferri M, Stazi MA, Raffaeli W. An Italian Twin Study of Non-Cancer Chronic Pain as a Wide Phenotype and Its Intensity. Medicina. 2022; 58(11):1522. https://doi.org/10.3390/medicina58111522
Chicago/Turabian StyleFagnani, Corrado, Virgilia Toccaceli, Michael Tenti, Emanuela Medda, Maurizio Ferri, Maria Antonietta Stazi, and William Raffaeli. 2022. "An Italian Twin Study of Non-Cancer Chronic Pain as a Wide Phenotype and Its Intensity" Medicina 58, no. 11: 1522. https://doi.org/10.3390/medicina58111522