Graduate Theses, Dissertations, and Problem Reports 2016 An Exploration of the Relationships between Chronic Pain, Inflammation, and Herbal Medicine Termeh Feinberg Follow this and additional works at: https://researchrepository.wvu.edu/etd Recommended Citation Feinberg, Termeh, "An Exploration of the Relationships between Chronic Pain, Inflammation, and Herbal Medicine" (2016). Graduate Theses, Dissertations, and Problem Reports. 5585. https://researchrepository.wvu.edu/etd/5585 This Dissertation is protected by copyright and/or related rights. It has been brought to you by the The Research Repository @ WVU with permission from the rights-holder(s). You are free to use this Dissertation in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you must obtain permission from the rights-holder(s) directly, unless additional rights are indicated by a Creative Commons license in the record and/ or on the work itself. This Dissertation has been accepted for inclusion in WVU Graduate Theses, Dissertations, and Problem Reports collection by an authorized administrator of The Research Repository @ WVU. For more information, please contact [email protected]. An Exploration of the Relationships between Chronic Pain, Inflammation, and Herbal Medicine Termeh Feinberg, MPH Dissertation submitted to the School of Public Health at West Virginia University in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Epidemiology Kim (Karen) Innes, M.S.P.H., Ph.D., Chair Christa Lilly, Ph.D. Dina Jones, P.T., Ph.D. Peter Giacobbi, Jr., Ph.D. Gilbert Ramirez, M.P.H., Dr.P.H., CPH Department of Epidemiology Morgantown, West Virginia 2016 Keywords: herb, inflammation, C-reactive protein, fibromyalgia, chronic pain, and epidemiology Copyright 2016. Termeh Feinberg, MPH ABSTRACT An Exploration of the Relationships between Chronic Pain, Inflammation, and Herbal Medicine Termeh Feinberg Introduction: Inflammation is often a component of chronic pain, yet its potential role in fibromyalgia syndrome (FMS) remains inconclusive. FMS is a complex chronic pain condition affecting ~2% of the population; management is challenging and treatment options remain limited. Many herbs contain antiinflammatory properties, and herbs indicated for analgesia and rheumatic conditions have traditionally been used in Appalachia. Despite the popularity of herbs in the US, determinants and patterns of herbal use with regard to pain management have not been well studied, particularly in Appalachia, where prevalence of chronic pain and related comorbid conditions is high and access to medical care is often reduced. In this series of three studies, we investigate the: 1) relation of FMS to serum C-reactive protein (CRP) in a large Appalachian population; 2) demographic, lifestyle, and health-related correlates of herbs and other complementary health approaches (CHAs) used for pain in a sample of Appalachian chronic pain patients, using a newly developed survey instrument; and, 3) the relation of herbal supplement use to FMS in two nationally representative samples of U.S. adults (NHIS 2007 and 2012), as well as trends in patterns of herbal use over time. Methods: All participants completed comprehensive health surveys in these three cross-sectional studies. To investigate the relation between diagnosed FMS and serum levels of the proinflammatory marker CRP (Study 1), we used data on 52,535 adult Ohio Valley residents (FMS =1,125), collected in 2005-2006 as part of the C8 Health Project. Medical history, including physician diagnosis of FMS, was ascertained via self-report. To determine the correlates and patterns of herbal and other CHAs used specifically for pain in an Appalachian chronic pain population (Study 2), we collected data on 301 patients from four WV pain and rheumatology clinics using our newly developed survey instrument, the Complementary Health Approaches for Pain Survey (CHAPS) (2014-2016); correlates relating specifically to pain were measured using the Short-Form Global Pain Scale (SF-GPS). To assess the relation of diagnosed FMS to herbal supplement use (at 30 days, past 12 months, and ever) and to examine potential changes in the patterns of use over time (Study 3), we used data from the 2007 and 2012 National Health Interview Surveys (NHIS) (N = 20127 and N = 30672 adults, respectively). Logistic and linear regression (complete-case analysis) were used to examine associations and to evaluate the potential modifying influence of gender and number of health conditions; multivariate models were adjusted for an array of demographic, lifestyle, and health factors. To account for missing data (Study 2), we also conducted additional sensitivity analyses using multiple imputation. Results: Study 1. In this large Appalachian population, mean serum CRP was significantly higher among participants reporting a diagnosis of FMS than those without FMS (5.54± 9.8 vs.3.75±7.2 mg/L, p<0.0001)). CRP serum level showed a strong, positive association with FMS (unadjusted OR for highest vs. lowest quartile=2.5 (CI 2.1,3.0; P for trend(p<0.0001); adjustment for demographics and lifestyle factors attenuated but did not eliminate this association (adjusted odds ratio (AOR) for highest vs. lowest quartile = 1.4, (CI 1.1, 1.6). The addition of body mass index (BMI) and comorbidities to the model further weakened the relationship between CRP and FMS (AORs, respectively, for highest vs lowest CRP quartile=1.2 (CI 1.0,1.4) and 1.1 (CI 0.9, 1.3), suggesting that these factors may partially explain the observed associations. Study 2: In our sample of 301 WV chronic pain patients, 8% reported using herbs and 58.8% reported using other CHAs, including mind-body practices (28.9%),; acupuncture, manipulative treatments, massage, and/or movement therapies (28.1%), and non-herbal dietary supplements (53.6%). Herbal use in this sample was marginally, inversely associated with age (OR adjusted for education=0.97 (CI 0.94,1.01) and positively associated with education (OR adjusted for age=4.94 (CI 1.6,15.3); Herbal use also showed strong positive associations with use of other CHAs ( (AOR=11.5 (CI 1.5,87.9); specific CHA AORs ranging from 2.4 to 10.3). Use of other CHAs was marginally, inversely associated with age (OR adjusted for education/exercise=0.98 (CI 0.96,1.0), and significantly and positively associated with education and physical activity (AOR’s for Bachelor’s+ vs. <HS/GED= 2.7 (CI 1.1,6.4; Exercise per 30 min p/w increment = 1.14 (CI 1.01,1.3); concomitant use of other CHAs was significantly and positively associated with all CHA categories after adjustment for multiple confounders. Neither herbal use nor CHA use overall was associated with pain severity or use of prescription medications. Sensitivity analyses using multiple imputation did not appreciably change any observed associations. Study 3. Prevalence of diagnosed FMS was significantly higher in 2012 compared to 2007 (1.7% vs. 1.3%), whereas reported use of herbs declined from 57 to 41% for ever use (p <0.0001). In both nationally representative samples of US adults (NHIS 2007, 2012), adults with FMS were significantly more likely to use herbs at 30 days, 12 months, or ever relative to adults without FMS; these positive associations remained highly significant even after controlling for a broad array of demographic, lifestyle, and health-related factors (Ranges: 2007 AOR’s = 2.3 – 2.7; 2012 AOR’s = 1.5 – 1.6; p’s<.0001). Conclusion: Results of these studies suggest that 1) FMS is positively associated with serum CRP, an association that may be largely explained by obesity and comorbidity, suggesting the role of inflammation in this chronic pain syndrome may be complex 2) CHA use specifically for pain in chronic pain patients in northern WV is high, and although overall reported use of herbs for pain is low, many herbs were reported by those disclosing herbal use; and 3) the use of herbs is strongly and positively associated with FMS diagnosis. Further prospective research is needed to confirm these findings, to further explore the role of inflammation in FMS to further investigate the patterns and determinants of herbal and related CHA use in FMS and other chronic pain populations, including those in Appalachia and other poor, underserved areas. DEDICATION I dedicate my doctoral dissertation to my husband, Josh Feinberg. Thank you for your kindness and patience throughout this part of our lives together. Your love, strength, and firm resolve to help others continues to inspire me greatly. ACKNOWLEDGEMENTS I express heartfelt gratitude to my dissertation committee chair, Dr. Kim Innes, who is largely responsible for my evolution to research scientist through her continual insights, guidance, and support. I admire you greatly. Your engagement in the fields of Integrative Medicine and Epidemiology strengthen my resolve to make a difference through great research. I have always been grateful for your feedback, and truly appreciate every push to help me think more critically. Thank you. I would also like to thank and acknowledge all other committee members for the various ways they have influenced and shaped me throughout my dissertation. Dr. Dina Jones, you have inspired me with the way you combine intellectual curiosity with your desire to help people. Your public health interventions are fueled by this passion, and you have taught me essential skills which have helped me balance organization, curiosity, and focus for my research. Dr. Christa Lilly, you have been a cheerleader and supporter when you have not been teaching me about statistics. I am forever grateful for your open door, and hope to exemplify the kind guidance you bestow on all of your students in my career. Dr. Peter Giacobbi and Dr. Gil Ramirez, thank you for teaching me how to think critically in the fields of Nutritional Epidemiology and Integrative Health.