Characterization of Whole Body Pain in Urologic Chronic Pelvic Pain Syndrome at Baseline - A MAPP Research Network Study

HHS Public Access Author manuscript Author Manuscript J Urol. Author manuscript; available in PMC 2017 September 01. Published in final edited form as: J Urol. 2017 September ; 198(3): 622–631. doi:10.1016/j.juro.2017.03.132. Characterization of Whole Body Pain in Urologic Chronic Pelvic Pain Syndrome at Baseline – A MAPP Research Network Study H. Henry Lai1,7, Thomas Jemielita2, Siobhan Sutcliffe3, Catherine S. Bradley4, Bruce Naliboff5, David A. Williams6, Robert W. Gereau IV7, Karl Kreder8, J. Quentin Clemens9, Larissa V. Rodriguez10, John N. Krieger11, John T. Farrar12, Nancy Robinson2, and J. Richard Landis2 For the MAPP Research Network13 Author Manuscript 1Division of Urologic Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO 2Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 3Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, MO 4Department of Obstetrics and Gynecology, University of Iowa School of Medicine, Iowa City, IA 5Department of Medicine and Psychiatry and Biobehavioral Sciences, University of California School of Medicine, Los Angeles, CA Author Manuscript 6Department of Anesthesiology, University of Michigan School of Medicine, Ann Arbor, MI 7Department of Anesthesiology and Washington University Pain Center, Washington University School of Medicine, St Louis, MO 8Department of Urology, University of Iowa School of Medicine, Iowa City, IA 9Department of Urology, University of Michigan School of Medicine, Ann Arbor, MI 10Departments of Urology and Obstetrics and Gynecology, University of Southern California, Los Angeles, CA 11Department of Urology, University of Washington School of Medicine, Seattle, WA 12Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA Author Manuscript Abstract Purpose—We characterized the location and spatial distribution of whole body pain among patients with urologic chronic pelvic pain syndrome (UCPPS) using a body map; and compared the severity of urinary symptoms, pelvic pain, non-pelvic pain, and psychosocial health among patients with different pain patterns. Corresponding Author: H. Henry Lai, MD, Division of Urologic Surgery, Department of Surgery, Washington University School of Medicine, 4960 Children’s Place, Campus Box 8242, St Louis, MO 63110, USA. 13List of MAPP Investigators in Appendix Lai et al. Page 2 Author Manuscript Methods—233 women and 191 men with UCPPS enrolled in a multi-center, one-year observational study completed a battery of baseline measures, including a body map describing the location of pain during the past week. Participants were categorized as having “pelvic pain only” if they reported pain in the abdomen and pelvis only. Participants who reported pain beyond the pelvis were further divided into two sub-groups based on the number of broader body regions affected by pain: an “intermediate” group (1–2 additional regions outside the pelvis) and a “widespread pain” group (3–7 additional regions). Author Manuscript Results—Of the 424 enrolled patients 25% reported pelvic pain only, and 75% reported pain beyond the pelvis of which 38% reported widespread pain. Participants with greater number of pain locations had greater non-pelvic pain severity (p<0.0001), sleep disturbance (p=0.035), depression (p=0.005), anxiety (p=0.011), psychological stress (p=0.005), negative affect scores (p=0.0004), and worse quality of life (p≤0.021). No difference in pelvic pain and urinary symptom severity were observed by increasing pain distribution. Conclusions—Three-quarters of men and women with UCPPS reported pain outside the pelvis. Widespread pain was associated with greater severity of non-pelvic pain symptoms, poorer psychosocial health and worse quality of life, but not worse pelvic pain or urinary symptoms. Keywords interstitial cystitis; chronic prostatitis; clinical phenotyping; widespread pain; pelvic pain Author Manuscript Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) or chronic prostatitis/ chronic pelvic pain syndrome (CP/CPPS) commonly report non-urologic symptoms or syndromes outside the pelvic region. There is also an association between IC/BPS, CP/CPPS and chronic overlapping pain syndromes (COPC) such as irritable bowel syndrome, fibromyalgia, and chronic fatigue syndrome1–3 with some studies reporting systemic (e.g., poly-symptomatic, poly-syndromic) symptom presentation.4, 5 It has been hypothesized that patients with localized pelvic pain might represent a different phenotype than those with more widespread systemic pain.6, 7 However to date, very few studies have characterized the location of body pain among men and women with IC/BPS or CP/CPPS. Author Manuscript Fitzgerald et al first reported that 11% of patients in the IC Database Study had “other” pain (e.g., whole body, one side, eyes, or kidney).8 Tripp et al used a whole-body diagram to characterize the location of pain in female IC/BPS patients.6 They found that as the number of body pain sites increased, patients experienced greater sensory pain, greater affective pain, higher depression scores, and diminished quality of life. Nickel et al found that female IC/BPS patients with “pelvic pain and beyond” also reported greater sleep disturbance and a higher prevalence of irritable bowel syndrome than female IC/BPS patients with “pelvic pain only.”9 Although these studies suggest the existence of distinct clinical subtypes in female patients, similar studies have not yet been performed in men, and no studies have examined the concept of widespreadness of body pain in either men or women. Findings in other chronic pain conditions suggest that patients with widespread pain have centralized pain characteristics.10–16 J Urol. Author manuscript; available in PMC 2017 September 01. Lai et al. Page 3 Author Manuscript Here we report the body pain mapping results of the Multi-disciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network from a large cohort of men and women with urologic chronic pelvic pain syndrome (UCPPS).17 UCPPS is an umbrella term used to describe IC/BPS in men and women, and CP/CPPS in men. To our knowledge, this is the largest body pain mapping study of UCPPS to date. Objectives of the study were to: (1) characterize the location of pain among men and women with UCPPS using a body map; (2) test the hypothesis that UCPPS patients with widespread pain have worse urinary symptoms, more severe pain, and poorer psychosocial health compared to those with more localized pain; and (3) examine if increased pain distribution is associated with longer duration of UCPPS symptoms. METHODS Author Manuscript Participants The MAPP Research Network enrolled 191 men and 233 women with UCPPS at six clinical sites across the United States. The study design, and inclusion and exclusion criteria have been described previously.18 To meet IC/BPS symptom criteria males and females had to report an unpleasant sensation of pain, pressure or discomfort, perceived to be related to the bladder and/or pelvic region associated with lower urinary tract symptoms, for most of the time during the most recent 3 months. Males who met CP/CPPS criteria had to report pain or discomfort in any of the 8 Male Genitourinary Pain Index (GUPI) domains and these symptoms had to have been present for most of the time during any 3 of the previous 6 months.19 Participants provided written informed consent following IRB-approved protocols. Author Manuscript Pain Assessment Author Manuscript The body map in Figure 1 was originally described by Margolis et al,20 and used by two previous IC/BPS studies.6, 9 Participants were asked to check any of 45 body sites on the body map where they experienced pain in the past week. Participants reporting pain in sites 14, 15 or 16 only were considered to have “pelvic pain only”.7 Participants reporting pain in any of the 7 broader body regions (in color) in addition to sites 14, 15, or 16 were considered to have “pelvic pain and beyond”. Our pelvic pain only versus pelvic pain and beyond nomenclature was similar to a previous mapping study by Nickel et al.7 The pelvic pain and beyond group was further divided into two subgroups as shown in Figure 1: an “intermediate” group with 1–2 additional pain regions outside the pelvis, and the “widespread pain” group with 3–7 additional pain regions outside the pelvis. The threshold for “widespread pain” was operationalized to divide participants with pelvic pain and beyond into two subgroups with approximately equal numbers of patients. Measures The MAPP Network questionnaires have been described previously.18 Urologic measures included: Interstitial Cystitis Symptom and Problem Indexes (ICSI, ICPI), Genitourinary Pain Index (GUPI), AUA Symptom Index (AUASI), RAND Interstitial Cystitis Epidemiology (RICE) instrument to assess bladder hypersensitivity,21 numeric ratings of pelvic pain, frequency or urgency, MAPP Composite Pelvic Pain Score, MAPP Composite J Urol. Author manuscript; available in PMC 2017 September 01. Lai et al. Page 4 Author Manuscript Urinary Score, and UCPPS flare assessment.22 Non-urologic and psychosocial measures included: a numeric rating from 0–10 for non-urologic or -pelvic pain, fulfillment of standardized criteria of irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, migraine headache, or vulvodynia using the Complex Multiple Symptoms Inventory (CMSI) modules,23 Brief Pain Inventory (BPI) for overall pain severity and pain interference, Hospital Anxiety and Depression Scale (HADS) for anxiety and depression, Positive and Negative Affect Scale (PNAS), Perceived Stress Scale (PSS) for psychological stress, Coping Strategies Questionnaires (CSQ) for pain catastrophizing, CMSI for somatic symptom burden, and PROMIS scales for fatigue and sleep disturbance. Quality of life measures included the SF-12 and GUPI. We limited our analyses to cross-sectional baseline data in this study. Statistical Analyses Author Manuscript Few data were missing (<5%) for the reported outcomes. No imputations or adjustments were performed and the missing data were excluded from the analysis. Means and standard deviations were reported for continuous variables and relative frequencies for categorical variables. To test for a linear gradient effect in the 3 groups an ordinal value was assigned to each group, such that widespread pain = 2, intermediate pelvic pain and beyond = 1, and pelvic pain only = 0. The non-parametric Jonckheere-Terpstra trend test was used for the analysis of ordered progression of the measure across the 3 groups.24 Analyses used SAS software 9.4(SAS Institute, Cary, NC). RESULTS Pain Localization Patterns and Duration of UCPPS Symptoms Author Manuscript Only one-quarter (25.5%) of UCPPS patients reported pelvic pain only, while three-quarters (74.5%) reported pelvic pain and beyond. The percentages of men and women in the pelvic pain only, intermediate, and widespread pain groups were shown in Table 1. Relative to men, women were more likely to experience more widespread pain (p-trend=0.039). There were no differences in the duration of UCPPS symptoms among the 3 pain groups (Table 1). Heat maps (Figure 2) show the proportion of participants who had pain in a specific location in each of the 3 pain groups. Pelvic Pain and Urinary Symptom Severity Author Manuscript Men and women demonstrated no difference in the severity of pelvic pain, urinary symptom (frequency, urgency), and bladder hypersensitivity features (e.g., painful bladder filling and/or painful urgency)21 among the 3 pain groups (p>0.05, Table 1). Women with a greater number of pain locations were more likely to report higher GUPI pain scores (p=0.033) and symptom flare at the time of visit (p=0.012). Non-Pelvic Pain Severity and Chronic Overlapping Pain Conditions (COPC) Men and women with a greater number of pain locations were more likely to report higher levels of non-pelvic pain severity (0–10 numeric ratings), and symptoms consistent with irritable bowel syndrome, fibromyalgia, and migraine headache (p<0.05, see Table 2). Women with a greater number of pain locations were also more likely to report higher pain J Urol. Author manuscript; available in PMC 2017 September 01. Lai et al. Page 5 Author Manuscript interference scores (BPI), and symptoms consistent with chronic fatigue syndrome and multiple (≥2) COPC. Psychosocial Health and Quality of Life Men and women with greater number of pain locations had greater sleep disturbance (PROMIS), depression, anxiety (HADS), psychological stress (PSS), somatic symptom burden (CMSI), and negative affect scores (PANAS) (p<0.05, Table 2). Women with a greater number of pain locations were also more likely to report pain catastrophizing (CSQ) and fatigue (PROMIS), and a decrease in positive affect (PANAS). While the more general physical health and mental health domains of the SF-12 deteriorated across the gradient of increasing pain distribution, no trend was noted for urinary specific quality of life on the GUPI in either men or women. Author Manuscript Comparison of the Two Subgroups with Pelvic Pain and Beyond Author Manuscript Individuals commonly report pain in parts of their bodies from time to time (e.g., >40% of participants reported back pain or headache). To determine whether patients in the “intermediate” group with a limited distribution of pain outside the pelvis had a different presentation than those with “widespread pain”, we performed additional comparisons of the two subgroups (Table 3). Men and women with widespread pain reported more severe nonpelvic pain, and were more likely to have fibromyalgia, depression, higher psychological stress, higher somatic symptom burden, and worse physical health (SF-12) than men and women in the intermediate group.. Men with widespread pain were additionally more likely to have migraine headache, anxiety, pain catastrophizing, more negative affect and less positive affect; while women with widespread pain were additionally more likely to have irritable bowel syndrome, chronic fatigue syndrome, multiple (≥2) COPC, sleep disturbance, fatigue, and worse mental health (SF-12) than their respective intermediate group. In both sexes, there was no difference in pelvic pain and urinary symptom severity between the two subgroups. DISCUSSION Author Manuscript Despite being enrolled because of their UCPPS, most patients in this large multi-site study (75%) reported additional pain outside the pelvis/abdomen, and 38% reported a widespread pain distribution. In both men and women, increasing anatomic pain distribution was associated with greater non-pelvic pain severity, a higher prevalence of chronic overlapping pain conditions, poorer psychosocial health, and worse quality of life. In contrast, there was no difference in the severity of pelvic pain and urinary symptoms among the three pain subgroups. UCPPS patients with widespread pain appeared to be distinct from patients with more limited distribution of pain outside the pelvis (the intermediate group) as shown in Table 3. Our overall findings were consistent with the previous studies: women with IC/BPS and systemic pain were more likely to have more severe overall pain, other pain syndromes, and worse quality of life than women who reported pelvic pain only.6, 9 Previous body pain J Urol. Author manuscript; available in PMC 2017 September 01. Lai et al. Page 6 Author Manuscript mapping studies did not include men.6, 9 Here we studied a large cohort of men with IC/BPS or CP/CPPS, and demonstrated many similar findings in both sexes. Author Manuscript Body pain mapping may confer important information suggesting discrete UCPPS patient subgroups. Pain involving several body regions is likely to represent systemic pathophysiology characterized by centralized pain characteristics (e.g., driven by central sensitization and/or neuro-immune processes). Although the operational definitions of widespread pain varied between studies, literature from other chronic pain conditions suggests that the subgroup of patients with widespread pain may have more severe pain, decreased pain thresholds, and a centralized pain phenotype.10–16 For instance, patients with temporomandibular disorders and widespread pain had reduced pressure pain thresholds in both cranial and extra-cranial regions compared to similar patients with more localized pain.10 Patients with epicondylitis and multidisciplinary pain clinic patients with widespread pain also had lower pressure pain thresholds or increased central sensitization than similar patients with localized pain.11, 12 Here we have shown that a substantial proportion of UCPPS patients have widespread pain, and those with widespread pain have more intense whole body pain. Ongoing MAPP neuroimaging studies also suggest that UCPPS patients with widespread pain have altered brain structure and function.25, 26 In future studies we shall examine the pain thresholds and quantitative sensory testing data on these patients. Author Manuscript Assessing the severity of pelvic pain, urinary symptoms (frequency, urgency), or bladder hypersensitivity (e.g., painful bladder filling, painful urgency)21 alone cannot distinguish between the pelvic pain only group and the widespread pain group. Instead, the body map might identify patients who may have a more centralized pain syndrome possibly related to central sensitization. The body pain map may also be used to screen patients who may benefit from clinical evaluation for other chronic overlapping pain conditions (COPC). For example, among women with UCPPS in the widespread pain subgroup, 48% had irritable bowel syndrome, 26% had fibromyalgia, 31% had chronic fatigue syndrome, and 42% had migraine headaches. Among men with UCPPS in the widespread pain subgroup, these percentages were 34%, 13%, 5% and 24%, respectively. Women with widespread pain were more likely to have multiple (≥2) COPC. Despite widespreadness of pain being a cardinal component of fibromyalgia, it should be noted that relatively few UCPPS patients with widespread pain met the criteria for fibromyalgia (only 13% of men and 26% of women).27 The difference being that besides widespread pain, fibromyalgia also requires other symptoms (e.g., fatigue, somatic symptoms). The body pain map might also be used to screen for patients with high psychosocial burden (depression, anxiety, psychological stress, negative affect, pain catastrophizing). The body pain map (Figure 1) is simple to use, and can be included in the evaluation of IC/BPS and CP/CPPS. Author Manuscript Clinicians should consider the use of clinical phenotyping so they may tailor treatment to patients with UCPPS. It is possible that body pain mapping may be useful for categorization of the heterogeneous UCPPS population, and may inform more rational management strategies. For example, one might hypothesize that patients with bladder hypersensitivity features21 and localized “pelvic pain only” may be more likely to benefit from bladdercentric treatments (e.g., intravesical instillation, or pentosanpolysulfate). One might also hypothesize that UCPPS patient subpopulations with widespread pain might be less likely to J Urol. Author manuscript; available in PMC 2017 September 01. Lai et al. Page 7 Author Manuscript benefit from bladder/pelvic-directed treatments alone and might require systemic therapies for centrally mediated mechanisms (e.g., using tricyclic antidepressants, gabapentinoids, SNRI, or multidisciplinary pain management). Because many patients with widespread pain report increased psychosocial difficulties, they may also benefit from multi-modal and multidisciplinary therapies. Using a “one size fits all” approach to treat IC/BPS or CP/CPPS patients without regards for their discrete clinical characteristics (e.g., localized versus systemic pain) and pathogenesis may lead to treatment failures. In part, these hypotheses may explain why most prior randomized controlled trials failed to demonstrate clinically significant benefits of treating the entire UCPPS population using similar therapies. This is an important area for future translational studies because currently there is no high level evidence (randomized controlled trials) supporting this personalized approach to managing UCPPS.28, 29 Author Manuscript There are potential weakness in this study: (1) we did not collect data on tobacco abuse, musculoskeletal trauma, myofascial pain, or medical conditions (e.g. osteoarthritis, rheumatoid arthritis) that may influence the distribution of pain; (2) It has been hypothesized that UCPPS patients might progress over time from localized pain to loco-regional pain to systemic pain (e.g. central sensitization).1, 4, 30 Our data as well as those from Nickel et al 9 did not show a correlation between the duration of UCPPS symptoms and increased body pain distribution. However we cannot infer longitudinal trend from these cross-sectional data (e.g., there are risks of recall bias), longitudinal studies are needed to determine if there is temporal progression from one body pain pattern to another over time. CONCLUSION Author Manuscript Three-quarters of men and women with UCPPS (IC/BPS or CP/CPPS) reported pain outside the pelvis. Widespread pain was associated with greater severity of non-pelvic pain symptoms, poorer psychosocial health and worse quality of life, but not worse pelvic pain or urinary symptoms. Supplementary Material Refer to Web version on PubMed Central for supplementary material. Acknowledgments Author Manuscript The MAPP Research Network acknowledges support through NIH grants U01 DK82315, U01 DK82316, U01 DK82325, U01 DK82333, U01 DK82342, U01 DK82344, U01 DK82345, and U01 DK82370. The Appendix listed the investigators in the MAPP Research Network. The NIDDK and MAPP Network investigators wish to thank the Interstitial Cystitis Association and the Prostatitis Foundation for their assistance in recruiting study participants and other network efforts. We thank the participants and staff from the following sites that participated in the MAPP Network: Northwestern University; University of California, Los Angeles; University of Iowa; Washington University; University of Washington; University of Michigan; University of Pennsylvania (Data Coordinating Core); University of Colorado Denver (Tissue Analysis & Technology Core); and Stanford University. We would also like to thank Dr. John Kusek and Dr. Chris Mullins at the NIDDK for critical review of the manuscript. This article reports independent research commissioned by the National Institutes of Health. The views expressed in this article are those of the authors and are not necessarily those of the National Institute of Diabetes and Digestive and Kidney Diseases or the Department of Health and Human Services. J Urol. Author manuscript; available in PMC 2017 September 01. Lai et al. Page 8 Author Manuscript References Author Manuscript Author Manuscript Author Manuscript 1. Nickel JC, Tripp DA, Pontari M, et al. Interstitial cystitis/painful bladder syndrome and associated medical conditions with an emphasis on irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome. J Urol. 2010; 184:1358. [PubMed: 20719340] 2. Warren JW, Howard FM, Cross RK, et al. Antecedent nonbladder syndromes in case-control study of interstitial cystitis/painful bladder syndrome. Urology. 2009; 73:52. [PubMed: 18995888] 3. Krieger JN, Stephens AJ, Landis JR, et al. 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Assignment of the pain groups: pelvic pain only (0 region), an intermediate group with pain beyond pelvis (1–2 regions), and widespread pain (3–7 regions). Author Manuscript Author Manuscript J Urol. Author manuscript; available in PMC 2017 September 01. Lai et al. Page 11 Author Manuscript Figure 2. Author Manuscript The numbers on the heat maps refer to the proportion of participants, within of the 3 defined subgroups, who experienced pain at that site. Author Manuscript Author Manuscript J Urol. Author manuscript; available in PMC 2017 September 01. Author Manuscript Author Manuscript Author Manuscript Author Manuscript Table 1 Men (n = 191) Lai et al. Demographics, comparison of pelvic pain and urinary symptom severity. Women (n = 233) Pelvic Pain and Beyond Pelvic Pain and Beyond J Urol. Author manuscript; available in PMC 2017 September 01. Pelvic Pain Only (0 region) Intermediate (1–2 regions) Widespread Pain (3–7 regions) 57 (29.8) 72 (37.7) 62 (32.5) 48.4 (16.1) 46.7 (14.9) 45.5 (15.2) Race: White, n (%) 53 (93) 63 (87.5) Ethnicity: Hispanic, n (%) 1 (1.8) 3 (4.2) Duration of symptoms, mean years (SD) 8.7 (11.9) Duration of symptoms <1 years, n (%) p value (3 group trend) p value (3group trend) Pelvic Pain Only (0 region) Intermediate (1–2 regions) Widespread Pain (3–7 regions) 51 (21.8) 88 (37.7) 94 (40.3) 0.311 40.4 (13.4) 40.3 (14.9) 40.9 (14.5) 55 (88.7) 0.465 47 (92.2) 80 (90.9) 85 (90.4) 0.745 6 (9.7) 0.051 3 (5.9) 10 (11.4) 5 (5.3) 0.584 7 (9.3) 7.9 (11.2) 0.323 8.6 (9.5) 6.5 (7.8) 11.9 (12.6) 0.100 5 (8.8) 4 (5.6) 9 (14.5) 0.235 3 (5.9) 6 (6.8) 8 (8.5) 0.612 Age at diagnosis of IC/BPS, mean years (SD) 39.2 (12.9) 40.4 (13.1) 39.9 (13.1) 0.795 20 41.8 (13.1) 31.1 (12.1) 0.547 Age at diagnosis of CP/CPPS, mean years (SD) 49.2 (14.4) 44.6 (16.5) 39.8 (13.2) 0.12 NA NA NA NA Central acting (e.g., pregabalin, tricyclics) 26 (45.6) 29 (40.3) 29 (46.8) 0.875 23 (45.1) 36 (40.9) 43 (45.7) 0.799 Peripheral acting (e.g., pentosan polysulfate) 12 (21.1) 6 (8.3) 5 (8.1) 0.034 8 (15.7) 25 (28.4) 19 (20.2) 0.891 4 (7) 6 (8.3) 6 (9.7) 0.602 2 (3.9) 11 (12.5) 14 (14.9) 0.071 15 (26.3) 31 (43.1) 22 (35.5) 0.328 18 (35.3) 16 (18.2) 18 (19.1) 0.067 No. of participants, n (%) Demographics: Age, mean years (SD) 0.809 Medication Class: Opioids None Urologic and Pelvic Pain Severity: Pelvic pain (numeric ratings, 0–10) 4.5 (2.3) 5 (2.2) 0.844 5.1 (2) 5.1 (2.1) 5.5 (2.3) 0.243 4.7 (2.5) 5.1 (2.3) 0.896 5 (2.2) 5.2 (2.3) 5.7 (2.4) 0.061 GUPI Pain score (0–23) 12.2 (3.7) 12 (4.5) 12.4 (4.5) 0.85 12.3 (4.1) 12.3 (4.7) 13.7 (4.7) 0.033* a MAPP Composite Pain Score (0–28) 13.5 (4.8) 14.2 (5.6) 14.4 (5.6) 0.409 15.2 (5.1) 15.1 (5.8) 16.8 (5.7) 0.059 Page 12 5.1 (2.2) 5.1 (2.2) Overall urologic or pelvic pain symptoms (0–10) Author Manuscript Author Manuscript Women (n = 233) Pelvic Pain and Beyond Intermediate (1–2 regions) Widespread Pain (3–7 regions) p value (3 group trend) Pelvic Pain Only (0 region) Intermediate (1–2 regions) Widespread Pain (3–7 regions) p value (3group trend) 5 (2.7) 4.4 (2.5) 4.7 (2.6) 0.692 5.1 (2.3) 5.4 (2.6) 5.5 (2.6) 0.403 4.8 (2.7) 4.4 (2.6) 4.7 (2.5) 0.856 4.9 (2.7) 4.9 (2.6) 5.4 (2.5) 0.157 Lai et al. Author Manuscript Pelvic Pain and Beyond Pelvic Pain Only (0 region) Author Manuscript Men (n = 191) Urinary Symptom Severity: Frequency (numeric ratings, 0–10) Urgency (numeric ratings, 0–10) J Urol. Author manuscript; available in PMC 2017 September 01. GUPI Urinary score (0–10) 5 (3.1) 4.2 (2.8) 5.1 (2.7) 0.68 5.6 (2.8) 5.5 (3) 6 (3.1) 0.285 12.6 (6.9) 10.3 (5.9) 11.4 (5.7) 0.483 13.3 (5.7) 13 (6) 14.3 (6.4) 0.204 14.7 (8.5) 12.9 (7.3) 14.4 (9) 0.632 15.6 (6.9) 15.7 (8.9) 18.2 (9) 0.075 IC symptom index (0–20) 8.9 (5.1) 8.3 (4.6) 8.3 (4.4) 0.665 10.5 (4.4) 10.3 (4.4) 11.3 (4.6) 0.172 IC problem index (0–16) 7.8 (4.8) 6.9 (4.4) 7.4 (4.4) 0.72 9.2 (3.9) 9.1 (4) 10 (4.1) 0.132 GUPI Total score (0–45) 24.9 (7.2) 23.5 (8.7) 25.6 (8.2) 0.739 25.6 (8.5) 25.5 (9.3) 27.8 (8.7) 0.119 B: 24.6% E: 33.3% N: 42.1% B: 20.8% E: 41.7% N: 37.5% B: 29.0% E: 27.4% N: 43.6% 0.875 B: 24.6% E: 33.3% N: 42.1% B: 20.8% E: 41.7% N: 37.5% B: 29.0% E: 27.4% N: 43.6% 0.0856 10 (17.5) 18 (25) 18 (29) 0.146 10 (19.6) 27 (30.7) 37 (39.4) 0.012* MAPP Composite Urinary Score (0– 25) a AUA Symptom Index (0–35) Composite Scores: Bladder hypersensitivity (RICE): Both, Neither, Either b Flare occurring at baseline visit (yes/ no), n (%) Trend p-values were obtained from the non-parametric Jonckheere-Terpstra Test. a Griffith et al (2016). b Lai et al (2015). Page 13 Author Manuscript Author Manuscript Author Manuscript Author Manuscript Table 2 Men (n = 191) Women (n = 233) Pelvic Pain and Beyond Pelvic Pain Only (0 region) Lai et al. Comparison of non-pelvic pain severity, psychosocial, and quality of life measures. Pelvic Pain and Beyond J Urol. Author manuscript; available in PMC 2017 September 01. Intermediate (1–2 regions) Widespread Pain (3–7 regions) p value (3 group trend) Pelvic Pain Only (0 region) Intermediate (1–2 regions) Widespread Pain (3–7 regions) p value (3 group trend) 1.3 (1.6) 2.6 (2.5) 4.2 (2.5) <.0001* 1.5 (2) 3.4 (2.7) 5.1 (2.4) <.0001* Pain severity, BPI (0–10) 2.9 (2.1) 2.8 (2.4) 4.1 (2.8) 0.029* 3.3 (2.5) 4 (2.8) 4.9 (2.9) 0.001* Pain interference, BPI (0–10) 3.5 (1.9) 3.7 (2) 4.1 (2.1) 0.131 3.7 (1.8) 4 (1.8) 4.8 (1.9) <.0001* 9 (15.8) 21 (29.2) 21 (33.9) 0.028* 5 (9.8) 26 (29.5) 45 (47.9) <.0001* Non-Urologic or Pelvic Pain Intensity: Overall non-pelvic pain (numeric ratings, 0–10) Brief Pain Inventory (BPI) whole body pain: COPC (Chronic Overlapping Pain Conditions), n (%) Irritable bowel syndrome Fibromyalgia 0 (0) 1 (1.4) 8 (12.9) 0.001* 3 (5.9) 2 (2.3) 24 (25.5) <.0001* Chronic fatigue syndrome 1 (1.8) 5 (6.9) 3 (4.8) 0.454 3 (5.9) 8 (9.1) 29 (30.9) <.0001* Migraine Headache 3 (5.3) 7 (9.7) 15 (24.2) 0.002* 4 (7.8) 28 (31.8) 39 (41.5) <.0001* NA NA NA NA 9 (17.6) 16 (18.2) 19 (20.2) 0.675 1 (1.8) 3 (4.2) 4 (6.5) 0.203 3 (5.9) 4 (4.5) 26 (27.7) <.0001* SF-12 Physical Health (0–100) 51.1 (8.7) 51.6 (8.4) 47.3 (9.5) 0.021* 51.9 (6.9) 45.8 (10) 41 (11.2) <.0001* SF-12 Mental Health (0–100) 47.8 (9.1) 44.4 (11.1) 41 (11.2) 0.001* 46.2 (8.7) 44.9 (10.5) 40.7 (10.3) 0.001* 7.6 (2.4) 7.1 (3.1) 8.1 (2.7) 0.34 7.7 (2.9) 7.7 (3) 8 (2.9) 0.471 4.7 (3.5) 4.9 (4.3) 6.8 (4.1) 0.005* 3.6 (3) 5 (3.9) 6.5 (4.8) <.0001* 6.5 (4) 7 (4.6) 8.8 (4) 0.004* 6.2 (3.9) 8 (4.4) 8.7 (5.2) 0.011* Vulvodynia Multiple (≥2) COPC? Quality of Life: GUPI urinary-specific quality of life (0–12) Psychosocial Health: Depression, HADS (0–21) Anxiety, HADS (0–21) 30.6 (6.8) 32 (7.3) 28.7 (7.6) 0.16 32.2 (7.8) 29.5 (7.3) 27.4 (8) 0.001* Negative affect, PANAS (5–50) 19.2 (7.1) 19.8 (7.7) 23 (7.3) 0.004* 18.8 (7.1) 21.1 (8.1) 23.5 (9) 0.001* Page 14 Positive affect, PANAS (5–50) Author Manuscript Author Manuscript Women (n = 233) Author Manuscript 13.8 (7.2) Pain Catastrophizing, CSQ (0–36) Pelvic Pain and Beyond Intermediate (1–2 regions) Widespread Pain (3–7 regions) p value (3 group trend) Pelvic Pain Only (0 region) 14.7 (7) 17.6 (6.9) 0.005* 13.7 (6.7) 10 (8) 9.5 (8.2) 12.6 (9.2) 0.119 Somatic burden last year, CMSI (0– 39, Males; 0–41, Females) 6.9 (3.6) 8.4 (4.5) 11.9 (6.5) Somatic burden lifetime, CMSI (0– 39, Males; 0–41, Females) 9.3 (10.2) 10.9 (10) Fatigue, PROMIS T Score (29.4– 83.2) 51.9 (6.2) Sleep disturbance, PROMIS T Score (28.9–76.5) 51.1 (7.1) Stress, PSS (0–40) J Urol. Author manuscript; available in PMC 2017 September 01. Intermediate (1–2 regions) Widespread Pain (3–7 regions) p value (3 group trend) 16.5 (7.7) 20 (9) <.0001* 12.4 (7.9) 13.7 (8.2) 15.5 (9.5) 0.042* <.0001* 8.3 (5.4) 11.9 (7) 17.8 (9.2) <.0001* 8.9 (8.5) 0.873 8 (8.4) 10.3 (9.5) 11.7 (8.4) 0.003* 51.7 (7.2) 53.9 (6.5) 0.08 51.7 (6.4) 54.9 (6.8) 57.9 (7.1) <.0001* 51.9 (9.4) 55.1 (9.3) 0.035* 52.3 (8.8) 54.9 (9) 58.7 (9.2) <.0001* Lai et al. Pelvic Pain and Beyond Pelvic Pain Only (0 region) Author Manuscript Men (n = 191) Trend p-values were obtained from the non-parametric Jonckheere-Terpstra Test. Page 15 Author Manuscript Author Manuscript Author Manuscript Author Manuscript Table 3 Men (n=134) Women (n=182) p value** Intermediate (1–2) vs. Widespread Pain (3–7) p value** Intermediate (1–2) vs. Widespread Pain (3–7) Pelvic pain (numeric ratings, 0–10) 0.192 0.254 Overall urologic or pelvic pain symptoms (0–10) 0.394 0.12 GUPI Pain score (0–23) 0.616 0.052 MAPP Composite Pain Score (0–28) a 0.896 0.073 Frequency (numeric ratings, 0–10) 0.558 0.403 Urgency (numeric ratings, 0–10) 0.621 0.157 Comparison of the 2 subgroups with Pelvic Pain and Beyond Lai et al. Intermediate versus widespread pain subgroup comparison. Urologic and Pelvic Pain Severity: J Urol. Author manuscript; available in PMC 2017 September 01. Urinary Symptom Severity: GUPI Urinary score (0–10) 0.069 0.285 MAPP Composite Urinary Score (0–25) a 0.208 0.204 AUA Symptom Index (0–35) 0.501 0.075 IC symptom index (0–20) 0.802 0.103 IC problem index (0–16) 0.519 0.124 GUPI Total score (0–45) 0.242 0.125 Bladder hypersensitivity (RICE): Both, Either, Neither b 0.971 0.256 Flare occurring at baseline visit (yes/no), n (%) 0.56 0.182 <.0001* <.0001* Pain severity, BPI (0–10) 0.006* 0.036* Pain interference, BPI (0–10) 0.324 0.003* Irritable bowel syndrome 0.558 0.011* Fibromyalgia 0.008* <.0001* Composite Scores: Non-Urologic Pain: Overall non-pelvic pain (numeric rating, 0–10) Brief Pain Inventory (BPI) whole body pain: COPC (Chronic Overlapping Pain Conditions): N (%) Page 16 Author Manuscript Author Manuscript Author Manuscript Author Manuscript Women (n=182) p value** Intermediate (1–2) vs. Widespread Pain (3–7) p value** Intermediate (1–2) vs. Widespread Pain (3–7) Chronic fatigue syndrome 0.608 <.0001* Migraine Headache 0.024* 0.176 Comparison of the 2 subgroups with Pelvic Pain and Beyond Vulvodynia NA 0.729 0.553 <.0001* SF-12 Physical Health (0–100) 0.006* 0.005* SF-12 Mental Health (0–100) 0.071 0.017* GUPI urinary quality of life score (0–12) 0.092 0.463 Depression, HADS (0–21) 0.003* 0.036* Anxiety, HADS (0–21) 0.007* 0.407 Positive affect, PANAS (5–50) 0.008* 0.104 Negative affect, PANAS (5–50) 0.006* 0.058 Stress, PSS (0–40) 0.016* 0.01* Pain Catastrophizing, CSQ (0–36) 0.043* 0.196 Somatic burden last year, CMSI (0–39, Males; 0–41, Females) 0.003* <.0001* Somatic burden lifetime, CMSI (0–39, Males; 0–41, Females) 0.291 0.096 Fatigue, PROMIS T Score (29.4–83.2) 0.09 0.01* Sleep disturbance, PROMIS T Score (28.9–76.5) 0.063 0.008* Multiple (≥2) NUAS? Lai et al. Men (n=134) Quality of Life: J Urol. Author manuscript; available in PMC 2017 September 01. Psychosocial Health: ** The numeric values have already presented in Tables 1 & 2. To examine if there were differences between the intermediate and widespread pain groups, a Chi-square test was used for binary variables of interest while a Wilcoxon-Mann-Whitney test was used for continuous or ordinal variables of interest with a 2-sided significance level of alpha = 0.05. a Griffith et al (2016). b Lai et al (2015). Page 17