br School of Nursing Duke University
*School of Nursing, Duke University, Durham, North Carolina, ySchool of Nursing, University of Pittsburgh, Pittsburgh, Pennsylvania, zSchools of Medicine, University of California, San Francisco, California, xSchools of Nursing, University of California, San Francisco, California
Abstract: Persistent arm pain is a common problem after breast cancer surgery. Little is known about genetic factors that contribute to this type of postsurgical pain. Study purpose was to explore associations between persistent arm pain phenotypes and genetic polymorphisms among 15 genes involved in catecholaminergic and serotonergic neurotransmission. Women (n = 398) rated the pres-ence and intensity of arm pain monthly for 6 months after breast cancer surgery. Three distinct latent GS-5734 of patients were identified (ie, no arm pain [41.6%], mild arm pain (23.6%), and moderate arm pain (34.8%). Logistic regression analyses were used to evaluate for differences between genotype or haplotype frequencies and the persistent arm pain classes. Compared with the no arm pain class, 3 single nucleotide polymorphisms and 1 haplotype, in 4 genes, were associated with membership in the mild arm pain class: COMT rs4633, HTR2A haplotype B02 (composed of rs1923886 and rs7330636), HTR3A rs1985242, and TH rs2070762. Compared with the no arm pain class, 4 single nucleotide poly-morphisms in 3 genes were associated with membership in the moderate arm pain class: COMT rs165656, HTR2A rs2770298 and rs9534511, and HTR3A rs1985242. Findings suggest that variations in catecholaminergic and serotonergic genes play a role in the development of persistent arm pain.
Perspective: Limited information is available on genetic factors that contribute to persistent arm pain after breast cancer surgery. Genetic polymorphisms in genes involved in catecholaminergic and serotonergic neurotransmission were associated with 2 persistent arm pain phenotypes. Findings may be used to identify patients are higher risk for this common pain condition.
Key words: Arm pain, persistent pain, postsurgical pain, polymorphisms, catecholaminergic genes, serotonergic genes, breast cancer.
Surgery is the primary treatment for breast cancer. Unfortunately, 25 to 60% of patients report persis-tent postsurgical pain after breast cancer sur-
gery.2,19 This pain usually occurs about 12 weeks after surgery and is characterized by burning, throbbing, or aching in the ipsilateral chest, axilla, and/or arm. This
pain is associated with other breast and arm symptoms, including swelling and weakness. Although previous
studies have identified various demographic and clini-cal risk factors,1,5,31,40,42,57 as well as physiological fac-tors (eg, genetic variations9,32,39,64) associated with the development of persistent pain after breast cancer
Funded by grants from the National Cancer Institute (NCI, CA107091 and CA118658). This project was supported by NIH/NCRR UCSF-CTSI Grant Number UL1 RR024131. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Dr. Knisely was supported by a National Institute of Nursing Research T32 postdoctoral fellowship (NR0097590). Dr. Miaskowski is an Ameri-can Cancer Society Clinical Research Professor and is funded by the NCI (CA168960). The authors have no conflicts of interest to declare.
Supplementary data accompanying this article are available online at www.jpain.org and www.sciencedirect.com.
Address reprint requests to Christine Miaskowski, RN, PhD, Professor and Vice Chair for Research, Department of Physiological Nursing, Univer-sity of California, 2 Koret Way − N631Y, San Francisco, CA 94143-0610. E-mail: [email protected]
ARTICLE IN PRESS
2 The Journal of Pain
surgery, its exact etiology remains elusive. Inconsisten-cies exist in the characterization of this persistent post-surgical pain that hinder our understanding of the underlying mechanisms.
Previously, we reported on distinct phenotypic charac-terizations of persistent breast42 and arm43 pain in a sample of 398 women who underwent breast cancer surgery. Using worst breast or arm/shoulder pain sever-ity scores over 6 months, growth mixture modeling (GMM) identified 4 distinct persistent breast pain phe-notypes (ie, no pain [31.7%], mild pain [43.4%], moder-ate pain [13.3%], and severe pain [11.6%]) and 3 distinct persistent arm pain phenotypes (ie, no pain [41.6%], mild pain [23.7%], and moderate pain
[11.6%]). When these persistent breast and arm pain classes were compared, distinct differences in demo-graphic and clinical characteristics between the 2 ana-tomic sites were identified.30 For example, when compared with breast pain, arm pain was described more similarly to neuropathic pain and showed less vari-ability in patterns of change over time.30 These findings suggest that persistent arm pain represents a different pain condition from persistent breast pain.