LY 294002 br Catecholamines eg dopamine norepinephrine
Catecholamines (eg, dopamine, norepinephrine, epi-
nephrine) and serotonin modulate pain transmission in the peripheral and central nervous systems.23,58,63,66
Alterations in these neurotransmitters are implicated in the development of persistent pain syndromes.4,15,50 A
number of reviews and meta-analyses have identified significant associations between polymorphisms in catecholaminergic (eg, catechol-O-methyltransferase [COMT]) and serotonergic genes (eg, 5-hydroxytrypta-mine receptor 2A [HTR2A]) and persistent pain syn-dromes (eg, chronic postsurgical pain,22 migraine headaches,35 fibromyalgia,33 and lumbar radicular pain6). In a previous article,28 we reported on a number of polymorphisms in catecholaminergic and serotoner-gic genes that were associated with our persistent breast pain phenotypes. However, because no studies have evaluated for associations between these 2 groups of genes and the development of persistent arm pain after breast cancer surgery, in this study we extend our previ-ous work using an extreme phenotype approach to eval-uate for associations between our persistent arm pain phenotypes (ie, no pain versus mild pain and no pain versus moderate pain) and genetic polymorphisms in the same 15 candidate genes involved in catecholamin-ergic and serotonergic neurotransmission. We hypothe-size that the genetic associations for persistent arm pain differ from those identified for persistent breast pain.
Patients and Settings
This analysis is part of a longitudinal study, funded by the National Cancer Institute, that evaluated for neuro-pathic pain and lymphedema in a sample of women who underwent breast cancer surgery. The methods used are described in detail elsewhere.39,42 In brief, patients were recruited from breast care centers located in a
Genetic Associations With Persistent Arm Pain
comprehensive cancer center, 2 public hospitals, and 4 LY 294002 practices. Patients were eligible to participate if they were an adult woman (≥18 years) who would undergo breast cancer surgery on 1 breast; were able to read, write, and understand English; agreed to partici-pate; and gave written informed consent. Patients were excluded if they were having breast cancer surgery on both breasts and/or were known to have distant metasta-sis at the time of diagnosis. A total of 516 patients were approached and 410 enrolled in the study. For this analy-sis, 398 women completed study questionnaires and 310 provided blood samples for genetic analyses.
A demographic questionnaire obtained information on age, education, ethnicity, marital status, employ-ment status, living situation, and financial status. The Karnofsky Performance Status (KPS) scale was used to evaluate patients’ functional status.26,27 The Self-Administered Comorbidity Questionnaire was used to
evaluate the occurrence of, treatment for, and impact of 13 common medical conditions.10,11,37,56,59 Patients
were asked to indicate if angina exercised on a regular basis (yes/no format).
Upper extremity pain was evaluated using the Arm/ Shoulder Symptoms Questionnaire and Postsurgical Pain Questionnaire. The Arm/Shoulder Symptoms Ques-tionnaire consisted of 2 parts. Part 1 obtained informa-tion on the occurrence of pain in the arm and shoulder area. If the patient had pain in the shoulder, arm, or hand, they completed part 2. Patients were asked to rate the intensity of their average and worst pain using a numeric rating scale that ranged from (no pain) to 10 (worst imaginable pain).25 The Arm/Shoulder Symp-toms Questionnaire was completed monthly for 6 months after surgery. The Postsurgical Pain Question-naire evaluated pain intensity in the first 24 to 48 hours after surgery. Average and worst pain were rated using a (no pain) to 10 (worst imaginable pain) numeric rat-ing scale. This Post-Surgical Pain Questionnaire was completed once during the month 1 study visit.
The study was approved by the Committee on Human Research at the University of California, San Francisco, and by the institutional review boards at each of the study sites. During the patient’s preoperative visit, a cli-nician explained the study to the patient and deter-mined her willingness to participate. For those women who were willing to participate, the clinician introduced the patient to a research nurse. The research nurse met with the women, determined eligibility, and obtained written informed consent before surgery. After obtain-ing the consent, patients completed the enrollment questionnaires (assessment 0).
Patients were contacted 2 weeks after surgery to sched-ule the first postsurgical appointment. The research nurse met with the patients either in their home or in the clinical research center at 1, 2, 3, 4, 5, and 6 months after surgery.