Complementary Approaches for Military Women with Chronic Pelvic Pain: A Randomized Trial

Introduction: Active-duty (AD) women suffer with chronic pelvic pain (CPP) while providers tackle diagnoses and treatments to keep them functional without contributing to the opioid epidemic. The purpose of this study was to determine the effectiveness of non-invasive, self-explanatory mindfulness-based stress reduction (MBSR) or self-paced healthy lifestyle (HL) interventions on CPP in AD women. Methods: We conducted a six-week interventional prospective study with AD women aged 21–55 at Mountain Home (MTHM), Idaho. Women were randomly assigned to MBSR (N = 21) or HL (N = 20) interventions. The primary outcome was pain perception. Secondary outcomes were depression and circulating cytokine levels. Results: Women in the MBSR group exhibited reduced pain interference (P < .01) and depression (P < .05) alongside decreased IL-4 (P < .05), IL-6 (P < .05), eotaxin (P < .05), MCP-1 (P = .06), and IL-1ra (P < .01) and increased VEGF (P < .05). Those in the HL group did not have changes in pain, however, did exhibit reduced depression (P < .05) alongside decreased GM-CSF (P < .05) and increased TNFα (P < .05), SDF-1 (P < .01), and IL-1ra (P < .01). Conclusion: AD women receiving MBSR or HL had reduced depression scores and altered circulating cytokine levels, however only those receiving MBSR had reduced pain perception. Findings support MBSR as an effective and viable behavioral treatment for AD women suffering from CPP. self-assessment nominal screening and diagnostic tool used in primary care clinics in the Department of Defense (DOD) and VA routinely for somatic symptoms in depression. The PHQ-9 scores each item from 0 to 3 providing a severity score ranging between 0 and 27. The scores 0, 1, 2, and 3 are assigned to the response categories referring to frequency of a particular symptom over the last two weeks with “not at all”, “several days”, “more than half the days”, and “nearly every day” respectively. 29 The severity of depression scores is graded as none/minimal (0–4), mild (5–9), moderate (10–14), moderately severe (15–19), and severe (20–27). The PHQ9 has a sensitivity of 51% and a specicity of 94%, high validity (AUROC 0.85, 95% CI 0.82–0.88). 29 The PHQ-9 has been used internationally as a criterion-based of mental disorders translated in 25 languages with adequate reliability, and construct and criterion validity in diverse samples. The DOD used the PHQ-9 in veterans and found adequate internal consistency (Cronbach’s α = 0.92, 95% CI = 1.86–19.13) and test-retest (0.84). 30 0.87]) and increased levels of tumor necrosis alpha (TNFα; P<.05, 95% CI [-9.65- 0.0]), stromal cell-derived factor 1 (SDF-1; P<.01, 95% CI [-1039- -193.1]), and IL-1ra (P<.01, 95% CI [-147.1--57.71]). This study was designed to evaluate the effectiveness of a non-invasive, self-explanatory MBSR or self-paced HL intervention primarily on CPP. Additionally, co-morbid depression, and inammation among AD women were assessed. We found that AD women receiving a 6-week MBSR intervention had signicant reductions in CPP. Further, women receiving either the MBSR or HL interventions had signicant reductions in depression alongside changes in plasma cytokine levels. While prior research has found MBSR and HL interventions effective for the management of CPP and related pain and health conditions, our results are the rst to demonstrate the benet of MBSR and HL in a population of AD women with CPP.


Introduction
Chronic pelvic pain (CPP) was de ned as noncyclic pain in the lower abdomen, back, or buttocks which is severe enough to require medical attention and is present for at least six months without successful treatment and expected to be lifelong 1 as this research was concluded prior to ACOG revising the CPP de nition in March 2020. CPP is common, affecting 15% of the US population. 2 CPP can be disabling and causes distress on women's quality of life (QOL) including physical functioning, psychological well-being, and interpersonal relationships. 2 In addition, the condition is often elusive and di cult for providers to diagnose. 2,3 Up to 55% of women continue to experience pain without obvious pathology even after surgical interventions. 4 Frustrated with persistent symptoms and lack of improvement, these women stop seeking help. 3,5 As of July 2017, 15% of women were actively serving in the United States (US) military (https://www.statisticbrain.com/women-in-the-military-statistics/). 6 These active duty (AD) women became combat deployable in 2016 after the US military o cially lifted the ban on female soldiers serving in combat roles www.theguardian.com/world/2013/jan/24/us-military-lifts-ban-women-combat. 7 While CPP in AD women has rarely been studied, one retrospective chart review reported 14% of female soldiers were seen for untreated pelvic pain during Operation Iraqi Freedom and Operation Enduring Freedom. 8 Compared to civilians, AD women are at greater risk for hysterectomy for their CPP, and for hysterectomy at an earlier age (35 vs 43 yrs, P < .0001). 9 Female veterans disproportionately suffer from CPP at an estimated prevalence of 30% and are more likely than male veterans to receive opioids for this pain. 10,11 This is concerning with the epidemic of opioid use disorders affecting an estimated 2 million Americans and the rate increasing not only in the civilian population but also among AD service members and veterans (SAMHSA, 2019). 12,13 Generally, women with CPP report a 45% rate of reduced productivity, 14 a de cit detrimental in a combat zone. Due to co-morbidities associated with pain syndromes and mental health illness, it is recommended to screen for psychiatric disorders in any female veteran with unexplained pain. 15 Lieutenant General Thomas Travis, the Surgeon General (SG) of the United States Air Force (USAF) in 2014, addressed the Subcommittee on the Defense of the Health Programs in the military stating our main goal was to maintain a ready force and our quadruple aim was "Readiness, better health, better care, and best value." The recent SG, Lieutenant General Dorothy Hogg, made this recommendation interminable. The American Congress of Obstetricians and Gynecologists (ACOG) considered awareness of female veterans' unique health care needs as essential to practice in obstetrics and gynecology nationwide. 16 It is imperative that we identify treatment approaches that are safe and effective for AD women with CPP.
The US Veterans Health Administration (VA) supports a biopsychosocial model assuming pain is in uenced by a variety of different physical, pathological, psychological, social, and environmental factors. 15 Female veterans with CPP screened positive for comorbid mood disorders at a rate of 31%, had lower healthy physical functioning scores, more medical symptoms, and higher numbers of days in bed because of illness at the VA. 15,17 A large body of work suggests a role for pro-in ammatory cytokines in the pathophysiology of CPP, 18-21 perceived stress and mood disorders (depression) 20 that often accompany CPP.
Alternative non-pharmacologic treatments such as mindfulness-based stress reduction (MBSR) or healthy lifestyle (HL) modi cations including diet and exercise have been shown to reduce pro-in ammatory cytokine levels 22,23 and are recommended for CPP. 24 These alternative treatments can lead to positive reappraisal, decrease biological stress pathways, and lower nociceptive excitability, thus breaking the self-sustaining cycle of pain and neurogenic in ammation. 25 However, these interventions have yet to be studied in the context of CPP in AD women. Thus, the purpose of the present study was to investigate the putative bene cial effects of non-invasive MBSR and HL interventions in AD women with CPP.

Materials And Methods
This interventional prospective study was approved by the University of Missouri-Kansas City Institutional Review Board, the TriService Nursing Research Program Human Research Protection O ce (HRPO), and the Wilford Hall HRPO o ce. All research was performed in accordance with relevant guidelines and regulations provided by these governing bodies and informed consent was obtained from all participants. Records of participant participation followed regulatory guidance including Federal Privacy Act, 5 USC 522a and its implementing regulations, the Health Insurance Portability and Accountability Act of 1996 (HIPAA), and 45 CFR Parts 160 and 164. Additionally, all regulatory criteria met an additional ethics review at the MTHM AFB to assure proper protocol was adhered to with minimal concern for coercion. This study was registered with the grant in clinicaltrials.gov NCT04104542 (09/26/2019) and was designed to compare pain perception (intensity and interference) primarily, and secondarily depression and in ammatory cytokine biomarkers in AD women with CPP after a 6-week online MBSR or HL program.
Participants were recruited from outpatient clinics in an USAF military treatment facility (MTF) at Mountain Home (MTHM) Air Force Base, Idaho. The MTF at MTHM has family practice, mental health, and women's health specialists who were able to assist with recruitment. The AD female population in Idaho includes Asian (N = 140 or 8.9%), Black (N = 59 or 3.7%), Hispanic (N = 146 or 9.3%), Mixed (N = 94 or 6%), White (N = 1128 or 72%).
Active-duty women with CPP, pain in the lower abdomen/back for greater than six months, were recruited through the Wilford Hall HRPO and the TriService Nursing Research Program HRPO at MTHM from June to August 2019 after assuring for participant protection. A preliminary eligibility assessment of interested participants was conducted via a telephone interview. A positive response to any of the following criteria in the initial interview led to exclusion: 1) age < 21 or age > 50; 2) menopausal, pregnant, or breastfeeding; 3) pelvic/abdominal surgery within 6 months; 4) vaginal/pelvic infection at time of enrollment (as potential confounder of cytokines drawn), underlying diseases (cancer, diabetes, autoimmune); 5) unavailable to commit three months to study; 6) no access to computer or able to get online. Initially, the list of participants came from the group practice managers (GPM) and local women's health and family practice providers who agreed to help with recruitment of women with speci c ICD 10 codes from their practice. A few women self-identi ed directly from yers and a poster used for recruitment and all participants approved the primary investigator access to record review to con rm diagnosis.
Once consent was signed and diagnosis con rmed, participants were asked to complete valid and reliable questionnaires including a demographics questionnaire, a pain questionnaire (the Brief Pain Inventory-BPI), a depression questionnaire (the Patient Health Questionnaire -PHQ9), and a mindfulness questionnaire (the Five Facets of Mindfulness -FFMQ), sent through the Research Electronic Data Capture (REDCap). Through REDCap, data was managed securely with an infrastructure programming allowing for the blinded assignment of these AD women with CPP to either the MBSR or the HL interventions. Once assigned, only the PI had oversight to manage the database.
MBSR, a complementary treatment with an emphasis on cultivating a focused, contemplative self-awareness, can help patients obtain self-regulation for health improvement in positive reappraisal coping. 26 The classic in-person MBSR class is the best way to learn mindfulness because of live interaction and group support, but is not always feasible. For this study, MBSR online-training consisted of classic journal and written guidance with YouTube videos found on palousemindfulness.com with weekly homework assignments, progress reports, and readings each woman could perform asynchronously for convenience. There was access to online support trainings for still and moving meditations. Each participant had access to a step-by-step guide on chapters to read from "Full Catastrophe Living" by Jon Kabat-Zin each week, the asynchronous daily mindfulness sessions, a journal, and an online guide from Dave Potter. Weekly readings and videos included a different focus. This group was required to set aside 30-minutes vedays weekly for their "homework" to remain in the study. The PI had no access of these trainings and relied on the participants acknowledgement of homework assignments. Week one focused on simple awareness, an introduction to the body scan, which is tuning in to the body and reconnecting to the physical self. Week two began sitting meditation. Week three introduced yoga and dealing with thoughts and distractions. Week four focused on oneminute breathing space, responding vs reacting. Week ve focused on turning toward the di culty instead of moving away from it. Week six focused on mountain and lake meditations and the sacred art of listening. Questionnaires were completed and lab samples collected at six-weeks.
The HL group had access to weekly voice-over slides that guided them in nutrition and exercise choices with a different focus each week. It was modeled after the Group Lifestyle Balance (GLB) course found at USAF bases used by Nutritional Medicine to work with patients with diabetes or weight concerns. This group was required to journal at least ve-days weekly entering their workouts and meals with a speci c target goal to meet by the end of the study. The PI was able to monitor daily journaling in the tness tracker and send weekly reminders. Week one introduced the program, the free tness tracker application recommendation (my tnesspal), and basic nutrition. Week two included slides that encouraged participants to focus on their goals with nutrition tips to help them meet their targets. Week three reviewed participant goals while offering suggestions for selecting foods while shopping. Week four focused on tness goals and training motivation. Week ve discussed interactive work calculation of "typical meals" for dining out at different restaurants. Week six reviewed strength training, progress, diaries, goals pending and met. Each member documented in my tnesspal and shared their diary with one of the authors (CDC). This free site helped the HL participant journal their diet and exercise daily and track their goals.
All AD members have access to a certi ed nutritionist trained in telephone coaching and these women were informed that this was still available if desired to help guide them. Many of the HL group were advised to use the fermentable oligo-, di-, mono-saccharides and polyols, or FODMAP diet due to their speci c type of CPP. All slides were forwarded to the HL participants and they could elect to watch them asynchronously, when it was convenient allowing for varying schedules.
Mindfulness was measured among participants in both the MBSR and HL groups. To measure mindfulness, a multifaceted construct characterized by a shift in attention resulting in observation of each moment experience without interpretation, elaboration, or analysis of that experience as an intentional and non-judgmental awareness, the FFMQ was used. 27 The FFMQ consists of subscales that measure the ve facets of mindfulness: observe, describe, act with awareness, nonreactivity, and nonjudging, with 39-statements on a 5-point Likert-type scale ranging from one to ve. 27 Facet scores range from 8-40, except for the nonreactivity facet, which ranges from 7-35.
Pain Perception (intensity and interference) were measured using the Brief Pain Inventory (BPI). The intensity of pain is measured by 4-items, (current as well as worst, least, and average in the past week) on 0 "no pain" to 10 "worst pain imagined" for the numerical scales. Seven activities describe the interference and include (general activity, mood, walking, work, relations with others, sleep, and enjoyment of life) where 0 refers to "no interference" and 10 "complete interference". 28 It is used in the military and can be completed in less than 5-minutes. It has established reliability (Cronbach's alpha ranges: 0.77 to 0.91), internal consistency, good to excellent test-retest values (ICC .84-.90) and construct validity α > .70 in seven of nine studies documenting pain in cancer patients, lower back pain, range of motion, muscle tenderness. 28 Depression was measured using the Patient Health Questionnaire (PHQ9), a 9-item Likert-type self-assessment nominal screening and diagnostic tool used in primary care clinics in the Department of Defense (DOD) and VA routinely for somatic symptoms in depression. The PHQ-9 scores each item from 0 to 3 providing a severity score ranging between 0 and 27. The scores 0, 1, 2, and 3 are assigned to the response categories referring to frequency of a particular symptom over the last two weeks with "not at all", "several days", "more than half the days", and "nearly every day" respectively. 29 The severity of depression scores is graded as none/minimal (0-4), mild (5-9), moderate (10)(11)(12)(13)(14), moderately severe (15)(16)(17)(18)(19), and severe (20)(21)(22)(23)(24)(25)(26)(27). The PHQ9 has a sensitivity of 51% and a speci city of 94%, high validity (AUROC 0.85, 95% CI 0.82-0.88). 29 The PHQ-9 has been used internationally as a criterion-based diagnosis of mental disorders translated in 25 languages with adequate reliability, and construct and criterion validity in diverse samples. The DOD used the PHQ-9 in veterans and found adequate internal consistency (Cronbach's α = 0.92, 95% CI = 1.86-19.13) and test-retest (0.84). 30 Blood draws were not standardized by time of day or menstrual cycles due to the limited time of day available for laboratory access for participants and the PI. Cytokine concentrations in plasma were measured using a multiplex electrochemiluminescence immunoassay kit developed by Meso Scale Discovery (MSD). The customized U-PLEX (Cat. #K15054D) assay consisted of the following analytes: GM-CSF, IFNg, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, TNFα, IL-1RA, MCP-1, SDF-1, and VEGFα. The assay was carried out according to the manufacturer's instructions. Frozen plasma samples were thawed on ice then diluted fourfold, run in duplicate, and analyzed using Discovery Workbench 4.0.12 software (MSD). Calibrators supplied by MSD were used to create standard curves and extrapolate sample concentration.
The collected data stored on REDCap was transferred to R version 3.5.0 for statistical analyses. Next, data was described using standard statistical methods such as frequency distribution, graphical displays of data, and application of the appropriate descriptive statistics to determine each variable's central tendency, distribution, and

Results
The analysis included 41 eligible evaluable participants (MBSR=21, HL=20) from MTHM. A high attrition was projected for the "online" treatments, but the last-minute deployment contributed to even higher attrition (30% versus 10%) for personal or professional obligations. The nal completion total for both groups was N=28, including 14 participants for each group with 12 HL serum samples and 13 MBSR serum samples. Furthermore, participants subjected to deployments (two from the HL and seven from the MBSR group) necessitated a shortened study for a post assessment (T2) at six-weeks instead of the initial projected eight-weeks. There were no signi cant differences found within the demographics between groups as seen in Table 1. Table 1 Demographics variability. Descriptive statistics were provided for subject characteristics and can be found in Table 1 provided. Categorical variables are reported with counts and percentages, while continuous variables are reported as medians and interquartile ranges. The primary outcome was considered change in scores on the BPI and secondarily, change in scores for FFMQ and PHQ-9 questionnaires. An a priori power analysis found that a sample size of N = 100 would be required to achieve a statistical power of 0.8, for an alpha level of 0.05 and an effect size of 0.5. Though underpowered with a sample size of N = 27, we maintained an alpha level of 0.05 to determine an effect size of 0.5 which is considered moderate to large.
The Mann-Whitney U (Wilcoxon signed rank) test was used to compare the distribution of values for each group determine differences between groups at baseline pre-intervention as well as within group differences for changes (pre-to post-intervention) in mindfulness facets, pain scores, depression scores, and cytokine levels. Statistical signi cance was de ned as P < .05. Due to the exploratory nature of cytokine analyses, no adjustment was made for multiple comparisons. We next evaluated the effectiveness of MBSR and HL on pain. Of the 28 participants who completed the study, 27 completed the BPI at both time points. There were no signi cant differences in BPI scores between MBSR and HL groups pre-intervention and no group differences observed in pain intensity at six-weeks post-intervention. However, at six-weeks post-intervention, women in the MBSR group exhibited signi cant reductions in pain interference (P<.01, 95% CI for median decrease in pain score [-3.0, -1.0]), over time, while those in the HL group did not (P<=.51, 95% CI for median decrease in pain score [-3.0-2.0]). See Figure 1.
We next evaluated the effectiveness of MBSR and HL on depression scores. All nine-questions were individually con rmed within each group with paired samples correlations. No signi cant differences in PHQ-9 scores were observed between MBSR and HL groups pre-intervention. Women in both the MBSR (P<.05, 95% CI for median decrease in depression score [-4.0-0.0]) and HL (P<.05, 95% CI for median decrease in depression score [-2.0-0.0]) groups had an overall signi cant reduction in depression score over time measured with the Total PHQ9. See Fig. 2.
Finally, we evaluated the effects of MBSR and HL on plasma levels of pro-and anti-in ammatory cytokines. As shown in Figure

Discussion
This study was designed to evaluate the effectiveness of a non-invasive, self-explanatory MBSR or self-paced HL intervention primarily on CPP. Additionally, co-morbid depression, and in ammation among AD women were assessed. We found that AD women receiving a 6-week MBSR intervention had signi cant reductions in CPP. Further, women receiving either the MBSR or HL interventions had signi cant reductions in depression alongside changes in plasma cytokine levels. While prior research has found MBSR and HL interventions effective for the management of CPP and related pain and health conditions, our results are the rst to demonstrate the bene t of MBSR and HL in a population of AD women with CPP.
The MBSR training signi cantly improved mindful actions for the MBSR group with a 24% reduction in pain interference scores and a 15% reduction in depression scores post-intervention. This nding is in line with published reports demonstrating that MBSR training improves pain and depression among patients with CPP. 22,31,32 Women in the MBSR group also exhibited signi cant changes in cytokine expression levels. Speci cally, levels of IL-4, IL-6, eotaxin, MCP-1, and IL-1ra were decreased and levels of VEGF were increased. Cytokines are small intracellular regulatory proteins secreted by immune cells in the periphery and neurons and glia in the central nervous system. 21 Pro-in ammatory cytokines increase the activity of nociceptors by direct receptor-mediated actions as well as by inducing the transcription of pain-relevant genes that promote long-term synaptic plasticity. 18 Meanwhile, antiin ammatory cytokines negatively regulate pro-in ammatory cytokine expression and signaling to resolve in ammation and reduce pain. 33 IL-6, eotaxin, and MCP-1 are pro-in ammatory cytokines whose levels are elevated in patients with CPP [34][35][36] such that higher levels are associated with greater pain. 37 Additionally, elevated levels of these cytokines are correlated with depressed mood 38,39 which often accompanies CPP. The nding that expression levels of these cytokines were reduced following the MBSR intervention suggests that mindfulness may reduce pain and improve mood through normalizing cytokine signaling.
IL-4 and IL-1ra are anti-in ammatory cytokines well-known to have analgesic effects, 33 and MBSR interventions that improve QOL, mood, and stress have been shown to increase their levels. 40 Thus, the nding that IL-4 and IL-1ra levels were decreased following MBSR was surprising, although in line with data from a study where plasma levels of IL-4 were elevated in endometriosis patients. 41 The nding that VEGF levels were increased following MBSR was also unexpected, as VEGF regulates angiogenesis and pain 42 and increased levels have been observed in patients with CPP. 43 Notably, the resolution of in ammation is an active process characterized by cyclical uctuations in cytokines and growth factors released by immune and other cells to regain physiological homeostasis. 44 Thus, measurement of cytokines at multiple time points following MBSR may be required to understand the impact of this intervention on regulating pro-versus anti-in ammatory cytokines throughout this process.
While women in the HL group did not have signi cant reductions in pain scores, they did exhibit a 12% reduction in depression scores at the completion of the intervention. This nding is like others demonstrating the positive impact of HL interventions on mood. Speci cally, a diet high in fruits, vegetables, whole grains, and antioxidants and low intake of animal foods has been associated with a decreased risk of depression. 45 Additional evidence demonstrates that exercise reduces depressive symptoms and improves QOL and physical function, independent of factors such as education or physical health. 46, 47 The HL women also exhibited signi cant changes in cytokine expression levels.
Speci cally, levels of GM-CSF decreased and levels of TNFα, SDF-1, and IL-1ra increased. GM-CSF is an important hematopoietic factor that can promote macrophage migration from the bone marrow, contributing to the in ammatory process observed in depressive disorders. 48 Anti-depressants, such as uoxetine, have been found to reduce plasma levels of GM-CSF associated with improved mood. 48,49 IL-1ra is a member of the IL-1 cytokine family that serves as an endogenous negative-feedback regulator to control potentially pathologic in ammatory events. 50 In addition to alleviating pain, IL-1ra improves mood in patients with depression and has been an important therapeutic target. 50 Thus, HL training may improve mood in women with CPP through normalizing GM-CSF and IL-1ra signaling.
We also observed intervention-dependent increases in levels of the pro-in ammatory cytokines TNFα and SDF-1. TNFα is a key regulator of immune function implicated in numerous health problems of immune origin including CPP 51 and depression. 52 SDF-1 is emerging as an important contributor to pelvic in ammatory diseases 53 and depressive mood disorders. 54 Long-lasting increases in TNFα and SDF-1 are maladaptive, however transient increases following HL interventions like exercise may be vital for adaptive responses to training that ultimately have bene cial effects on mood. Acute release of TNFα after exercise is necessary to induce anti-in ammatory cytokines (eg, IL-1ra) promoting resolution of in ammation, tissue repair, and improved mood. 55 Acute increases in SDF-1 following exercise training augment the function of myocytes 56 leading to regeneration of skeletal muscle and vascular tissues, respectively. While there is a gap in our understanding of speci c mechanisms whereby combined exercise and nutrition training improve depression, our ndings together with published results suggest that a HL stimulates immune, muscle, and other cells to secrete pro-and anti-in ammatory cytokines in uencing mood-relevant pathways.
The online MBSR and HL interventions allowed for self-care in a military setting with widest dissemination for training at the participant's own time. Using a web-based survey had several advantages including population accessibility, time savings, and reduced cost. Online resources can potentially reach more AD members. Professional demands in the military can be overwhelming for many and having a resource that is easily accessible to them anywhere can be life changing. Active participation in an online MBSR program which otherwise would not have been available, can potentially lead to less physiological reactivity in response to stressors, improving morbidity.
However, this study had several limitations. First, participants had to have access to emails and capability to open attached links. The sheer amount of survey requests using web-based systems to approach potential study participants invariantly led to respondent fatigue and unwillingness to participate by some. Second, the sample size was small, increasing the chance of a type I error, and was restricted to MTHM, which may limit generalizability. Third, nutrition and exercise were not monitored for the MBSR group. Additionally, monitoring for major life events was not included.
Future research should include comparisons using alternative MBSR trainings (classic model versus online-only MBSR) along with monitoring training for HL activities. Furthermore, a larger study focusing on the combined effects of MBSR and HL with a control arm measuring results over an extended period (6 months) would help understand sustainability and continued impact of the interventions. Discovering interventions bene cial in improving coping with chronic pain is relevant and necessary to future studies.
In summary, both MBSR and HL represent safe, effective, and feasible treatment options for AD women with CPP.
MBSR was superior in that it improved pain and related depression symptoms. Though HL did not have a signi cant effect on pain, it did reduce co-morbid depression and, thus, may have added bene t when used in combination with MBSR.  Changes in Depression Scores Following MBSR or HL Interventions.

Figure 3
Changes in Cytokine Levels Following the MBSR Intervention. Figure 4