br findings from our previous genetic association study of
findings from our previous genetic association study of catecholaminergic and serotonergic genes and persistent breast pain28 and findings from the current study support this hypothesis. The only genes that were associated with both persistent breast and arm pain after breast cancer surgery were HTR2A and HTR3A. In subsequent studies of postoperative pain, detailed information should be collected for breast pain and for arm pain.
Several study limitations need to be acknowledged. Although our sample was adequate in size and repre-sentative of breast cancer patients in the United States,
Table 5. Comparison of Genomic Markers for No Pain Versus Mild or Moderate Pain in the Breast Versus the Arm
GENE SNP OR HAPLOTYPE BREAST PAIN ARM PAIN
No pain versus mild pain "
No pain versus moderate pain — #
Abbreviations: ADRB2, beta-2-adrenergic receptor; ADRBK2, beta adrenergic receptor kinase 2; COMT, catechol-O-methyltransferase; Hap, haplotype; HTR2A, 5-hydroxytryptamine receptor 2A; HTR3A, 5-hydroxytryptamine receptor 3A; SNP, single nucleotide polymorphism; SLC6A2, solute-like carrier (SLC) family 6 member 2-noradrenaline transporter; SLCA3, SLC family 6 member 3-dopamine trans-porter; TH, tyrosine hydroxylase; TPH2, tryptophan hydroxylase 2.
Legend: ", increased risk for mild or moderate pain; #, decreased risk for mild or moderate pain; —, no genetic association identified
ARTICLE IN PRESS
10 The Journal of Pain
our findings warrant replication before any definitive conclusions can be drawn about the genomic findings. Furthermore, additional latent Thapsigargin and significant gene polymorphisms may be identified with a larger and more diverse sample. In addition, women were recruited through referrals from 20 surgeons at 7 differ-ent sites to enhance generalizability of the study’s find-ings. An evaluation of how surgical and postoperative pain management protocols impact the development of persistent postsurgical pain and genetic associations may increase our understanding of the mechanisms that underlie this persistent pain condition. Finally, varia-tions in catecholaminergic and serotonergic genes are associated with depression14 and anxiety.29 Future stud-ies should control for these symptoms in any genomic analyses.
1. Andersen KG, Duriaud HM, Jensen HE, Kroman N, Kehlet H: Predictive factors for the development of persistent pain after breast cancer surgery. Pain 156:2413-2422, 2015
2. Andersen KG, Kehlet H: Persistent pain after breast can-cer treatment: A critical review of risk factors and strategies for prevention. J Pain 12:725-746, 2011
3. Andersen S, Skorpen F: Variation in the COMT gene: Implications for pain perception and pain treatment. Phar-macogenomics 10:669-684, 2009
4. Becker S, Schweinhardt P: Dysfunctional neurotransmit-ter systems in fibromyalgia, their role in central stress cir-cuitry and pharmacological actions on these systems. Pain Res Treat 2012, 2012:741746
5. Belfer I, Schreiber KL, Shaffer JR, Shnol H, Blaney K, Morando A, Englert D, Greco C, Brufsky A, Ahrendt G, Kehlet H, Edwards RR, Bovbjerg DH: Persistent postmas-tectomy pain in breast cancer survivors: Analysis of clini-cal, demographic, and psychosocial factors. J Pain 14: 1185-1195, 2013
6. Bjorland S, Moen A, Schistad E, Gjerstad J, Roe C: Genes associated with persistent lumbar radicular pain; a system-atic review. BMC Musculoskelet Disord 17:500, 2016
7. Bortsov AV, Diatchenko L, McLean SA: Complex multilo-cus effects of catechol-O-methyltransferase haplotypes pre-dict pain and pain interference 6 weeks after motor vehicle collision. Neuromolecular Med 16:83-93, 2014
8. Brezo J, Bureau A, Merette C, Jomphe V, Barker ED, Vitaro F, Hebert M, Carbonneau R, Tremblay RE, Turecki G: Differences and similarities in the serotonergic diathesis for suicide attempts and mood disorders: A 22-year longitudi-nal gene-environment study. Mol Psychiatry 15:831-843, 2010
9. Broyles JM, Tuffaha SH, Williams EH, Glickman L, George TA, Lee Dellon A: Pain after breast surgery: Etiology, diag-nosis, and definitive management. Microsurgery 36:535-538, 2016
10. Brunner F, Bachmann LM, Weber U, Kessels AG, Perez RS, Marinus J, Kissling R: Complex regional pain syndrome
Genetic Associations With Persistent Arm Pain
This study is the first prospective, longitudinal study to examine associations between the occurrence and severity of persistent arm pain after breast cancer sur-gery and catecholaminergic and serotonergic genes. The elucidation of genetic factors that predispose patients to persistent arm pain has the potential to identify high-risk patients who warrant more aggressive postoperative pain management. Our findings warrant replication in women with breast cancer and in patients with other persistent postsurgical pain conditions.