Chronic pain conditions including vulvodynia, fibromyalgia, interstitial cystitis, and irritable bowel syndrome are now known to be frequently underdiagnosed and are much more prevalent than previously estimated.1–5 Despite their disparate clinical presentations, studies of specific pain disorders report similarities in their findings such as systemic sensitivity as illustrated with peripheral pain testing,6–9 similar alterations on functional magnetic resonance image scanning of the pain network-associated sites in the brain,6,8,10 and differences in descending pain modulation in the central nervous system.11–13 This realization has led to an interest in understanding the pattern of co-occurrence of these chronic pain conditions as well as in investigating common mechanisms that may underlie these conditions and explain their shared features.
We report on data from a population-based cohort study of women with and without vulvodynia in southeast Michigan that incorporated validated questionnaire-based screening scales for vulvodynia, fibromyalgia, interstitial cystitis, and irritable bowel syndrome. This analysis estimates the prevalence and co-occurrence of these conditions and their associated demographic risk factors.
MATERIALS AND METHODS
This cross-sectional analysis uses data from the 6-month follow-up survey of the Michigan Woman to Woman Study, a population-based, ethnically diverse cohort study of women with and without vulvodynia in southeast Michigan. The study was approved by the University of Michigan Medical institutional review board. Recruitment and survey methodology has been previously described.2 In brief, women ages 18 years and older were recruited using random digit dialing by trained interviewers (The Institute of Social Research, University of Michigan, Ann Arbor, Michigan). After random selection of one eligible woman within a household, informed consent was obtained and a brief telephone interview conducted. Women were then sent a more extensive online or written survey (based on participant choice), which assessed demographic characteristics, exposures, urogenital symptoms, and medical history. Follow-up surveys were sent every 6 months to assess changes in symptoms and diagnoses and potential risk factors.
Previously validated survey-based screening scales for several pain conditions were incorporated into the 6-month follow-up survey including a validated screen for vulvodynia,14 the Fibromyalgia Impact Questionnaire,15 the Rice High Specificity definition for interstitial cystitis,16 and the Rome II criteria for irritable bowel syndrome.17 The validated criteria for vulvodynia included having had more than 3 months of vulvar discomfort, located at the opening of the vagina, that had not resolved (provoked or unprovoked, primary or secondary).14 The criteria for interstitial cystitis included a combination of symptoms of urinary frequency and dysuria16 and that for fibromyalgia included the presence of chronic pain or discomfort in four quadrants of the body.15 Irritable bowel syndrome was predicted by a combination of abdominal pain associated with altered bowel frequency, function, or both.17
Initial weighting of the baseline sample to reflect the population of the four-county area of southeast Michigan was conducted. The weights incorporated 1) the probability of selection in the sample; 2) the nonresponse rate; and 3) a poststratification component using the specific age-county distribution of the population (see Reed et al2 for complete details on the weight construction).2 The weighted prevalence and 95% confidence intervals (CIs) were estimated for each condition. These weights were also used in the two-sample t tests and χ2 tests to investigate any differences between the women who filled out the 6-month survey compared with those who did not. Weighted t tests and χ2 tests replace the sample means, standard deviations, and percentages by the corresponding weighted versions in the relevant formula and are carried out routinely in standard statistical software packages. We used the Complex Samples Module of the PASW 18.0 for our purposes.
Odds of having vulvodynia, fibromyalgia, interstitial cystitis, and irritable bowel syndrome were investigated by means of separate weighted multiple logistic regression models, which have as primary independent variables the indicators denoting presence or absence of each of the other three comorbidities. Each model was further controlled for age, marital status, ethnicity, education, and an indicator for difficulty paying for basics, the variables previously found to be associated with the prevalence of vulvodynia in our previous article.2 These analyses were repeated replacing the individual comorbidity indicators by their sum, which denotes the frequency of other comorbidities. A similar logistic regression analysis was carried out with the presence or absence of multiple (two or more) comorbid pain conditions simultaneously. The relationships between the presence or absence of vulvodynia and the presence of the other comorbid pain conditions, singly and in specific combinations of two or three, were estimated using a weighted χ2 test.
Between September 2008 and September 2009, 2,542 women, ages 18 years and older, were recruited randomly from the four-county area of southeast Michigan. Of these, 1,940 (76.3%) completed both the baseline and 6-month follow-up surveys. Women who completed the 6-month follow-up survey were similar in age as those who did not (50.7 years compared with 51.1 years, P=.62), but respondents were more likely to be white (78.2% compared with 58.2%, P<.001), married (66.1% compared with 50.4%, P<.001), have at least a high school education (95.8% compared with 90.0%, P<.001), have a household income greater than $60,000 (53.5% compared with 39.3%, P<.001), rate their health as excellent or very good (53.5% compared with 44.6%, P<.003), and indicate they have little or no pain (65.4% compared with 57.3%, P=.004). Of those completing the 6-month follow-up survey, 1,890 (97.4%) completed all screening questions needed to predict the presence of vulvodynia, fibromyalgia, interstitial cystitis, and irritable bowel syndrome and were included in this analysis. Their mean age was 50.4 years (standard deviation 16.2); 76.8% were white, 16.2% black, 2.4% Hispanic, and 4.5% other ethnicities; 66.4% were married or living as married; 96.0% were high school graduates; 38.6% found it very hard or somewhat hard to pay for basics; and 64.1% had intercourse in the past 6 months.
The prevalence of the four chronic comorbid pain conditions, using weighted data, ranged from 7.5% (95% CI 6.2–9.0) for interstitial cystitis, 8.7% (95% CI 7.3–10.4) for vulvodynia, 9.4% (95% CI 8.1–11.0) for irritable bowel syndrome, to 11.8% (95% CI 10.1–13.7) for fibromyalgia (Fig. 1). This translates into 72,000–114,000 women in the four-county area with each of the conditions. The proportion of women with each diagnosis that screened positive for any of the conditions is shown in Figure 1. Overall, 72.9% (95% CI 70.2–75.4) of the 1,890 women with complete data on the four chronic pain conditions screened negative for all four conditions, and 19.1% (95% CI 17.0–21.4) reported having only one of the four conditions.
The adjusted odds ratios of having each of the chronic comorbid pain conditions when each of the other three was present are shown in Table 1. The odds of screening positive for vulvodynia was increased 2.3-fold to 3.3-fold when a woman reported having any of the three other chronic pain conditions. As the number of other chronic pain conditions increased from zero to three, the odds of having vulvodynia increased more than fivefold. Similar associations were seen with the other three comorbid disorders with the odds of multiple comorbid conditions occurring simultaneously being highest for those with fibromyalgia.
As suggested by Figure 2, the combinations of multiple disorders are not uniformly distributed. For example, the combinations of other disorders among women with and without vulvodynia vary with vulvodynia cases being more likely to have interstitial cystitis or irritable bowel syndrome but not fibromyalgia as a sole other comorbidity. However, those with fibromyalgia in combination with interstitial cystitis or irritable bowel syndrome were seen more commonly in women with vulvodynia than in those without this disorder (Fig. 2).
Figure 3 shows the weighted prevalence rates for all four comorbid conditions across specific age decades. The associations between demographic characteristics of women with each disorder are shown in Table 2. For vulvodynia, fibromyalgia, and interstitial cystitis, the prevalence rates exhibit an inverted U-shaped pattern as a function of age with maximal prevalence in middle age. In contrast, the pattern of change with age for irritable bowel syndrome is roughly U-shaped with an increase noted in older age groups. Vulvodynia varied with age, was increased in married women and in those with lower education, and was less prevalent in black women. Conversely, fibromyalgia was associated with increasing age, lower education, and greater difficulty paying for basics and was the only disorder with a suggestion of an increased prevalence among black women. When the relationship between these demographic factors and increasing numbers of chronic comorbid pain conditions was evaluated (data not shown), no association was noted with age or ethnicity, marital status, or higher education. However, screening positive for two or more conditions was associated with difficulty paying for basics. Furthermore, the odds of increasing numbers of disorders rose progressively among those having difficulty paying for basics such as food, clothing, or housing (odds ratio for difficulty paying for basics of 1.4, 1.8, and 2.4 for those with one, two, or three to four conditions, respectively; P<.05 for each).
We further assessed other characteristics of vulvar pain that might predict the co-occurrence of multiple comorbid pain conditions. Among those screening positive for vulvodynia, there was no association between age at onset of vulvodynia, duration of vulvodynia symptoms, or maximum severity of vulvar pain they ever had experienced with the presence of any of the three other chronic comorbid pain conditions (data not shown).
Over the past 10 years the substantial prevalence of chronic comorbid pain conditions has become increasingly evident. This is one of the first population-based studies to screen for and examine the association between vulvodynia and three other chronic comorbid pain conditions. Compared with women without vulvodynia, those with this condition are two to three times more likely to have one or more other chronic comorbid pain conditions.
The Institute of Medicine reports that at least 116 million persons in the United States have chronic pain, with national annual cost estimates of more than half a billion dollars.18 This report stresses the need for better data on the incidence and prevalence of pain to reduce the effect of pain and the resultant suffering it causes. Studies on a number of pain conditions such as fibromyalgia, temporomandibular joint disorder, interstitial cystitis, and irritable bowel syndrome indicate the high likelihood of co-occurrence of multiple chronic pain disorders19–24 and that the costs associated with a specific disorder are often substantially increased as a result of the other comorbid pain conditions present.25
Vulvodynia has not routinely been included in comorbidity studies of chronic pain conditions26 despite the similarities in systemic sensitivity as illustrated with peripheral pain testing,6–9 similar alterations on functional magnetic resonance image scanning of the pain network-associated sites in the brain,6,8,10 and differences in descending pain modulation in the central nervous system.11–13 This lack of inclusion of vulvodynia in many of the previous studies may be attributable in part to the previous lack of validated screening tests for vulvodynia.14,27 Chronic pain conditions, in general, are often underdiagnosed; thus, comorbidity is underestimated when only those who have been previously diagnosed clinically are included. In this population-based cohort of adult women in southeast Michigan, we determined the presence of vulvodynia and of fibromyalgia, interstitial cystitis, and irritable bowel syndrome using previously validated criteria.14–17 Although the prevalence based on these criteria may differ from that estimated using only in-office diagnoses, the criteria do provide an estimate of women who report symptoms characteristic of the disorders who may never have been diagnosed or sought treatment.
In a review of previous research on the overlap between chronic pain disorders, Rodriguez and colleagues24 reported on four substantial methodological shortcomings that undermined the strength of conclusions. These included 1) participants were drawn primarily from tertiary care clinics limiting generalizability; 2) inconsistencies in assessment, including use of case definitions, self-reported physician diagnoses, and review of International Classification of Diseases, 9th Revision codes; 3) predominance of women in studies; and 4) variability in control groups, including healthy individuals, those with other chronic illnesses, or those with their health status nonspecified. In previous studies, vulvodynia has been shown to be associated with other chronic pain conditions;28–32 however, these studies were conducted in clinical practices,22,29–31 were based on reported comorbidities that may have underestimated comorbid diagnoses, or both.31 The current study used a population-based sample reflecting the female population in southeast Michigan and verified screening-based criteria and hence provides further evidence of the substantial associations between these chronic pain disorders in the general population.
We found that although women with vulvodynia were more likely to have any one of the other comorbid disorders, 72.9% screened negative for all four entities, and only approximately half of those with any one disorder met criteria for at least one additional condition. This finding that having multiple comorbid pain conditions is a characteristic of only a subset of those with a pain condition has been previously described.19,20 The fact that some women present with multiple conditions and others report only one suggests differing pathophysiology, differences in the time of onset of (other disorders destined to occur later), or a lack of “central sensitivity” that may be the relevant neurologic condition that underlies this predominant grouping of comorbid pain conditions. Co-occurrence appears not to be universal, but rather may indicate a characteristic of a subset of those affected.
We found that the association between vulvodynia and the other chronic comorbid pain conditions was not randomly distributed. Others have found that as the number of comorbid pain conditions increases, the distribution of specific pain conditions is not uniform33,34 with the types of pain conditions present forming distinct patterns. Further study of these variations and the order in which these disorders appear may further clarify shared and differing pathophysiological mechanisms.
Strengths and limitations of this study exist. The availability of data derived from previously validated screening inventories allowed us to assess prevalence and co-occurrences of these typically underdiagnosed disorders. In addition, these data were available on a general community-based population minimizing the bias commonly encountered when enrolling from health care facilities. However, the sensitivity and specificity of screening tests are imperfect and hence some misclassification is likely to remain. However, validation studies suggest their use maximizes the ability to predict these conditions in large numbers of women in the community despite the known clinical underdiagnosis and misdiagnosis rates inherent in the evaluation of these conditions to date.
In conclusion, vulvodynia is associated with other chronic comorbid pain conditions such as fibromyalgia, interstitial cystitis, and irritable bowel syndrome, individually and in combination, and the presence of vulvodynia or any of the other comorbid pain conditions increases the likelihood that a woman will have one or more of the other chronic pain conditions. Further study on the relationships between these disorders and the differences between those with multiple comorbid pain conditions and those with no or a solitary pain disorder is anticipated to identify previously unrecognized, evidence-based subgroups that may indicate a common pathophysiology, natural history, treatment response, or a combination of these.
1. Harlow BL, Stewart EG. A population-based assessment of chronic unexplained vulvar pain: have we underestimated the prevalence of vulvodynia? J Am Med Womens Assoc 2003;58:82–8.
2. Reed BD, Harlow SD, Sen A, Legocki LJ, Edwards RM, Arato N, et al.. Prevalence and demographic characteristics of vulvodynia in a population-based sample. Am J Obstet Gynecol 2012;206:170.e1–9.
3. White KP, Speechley M, Harth M, Ostbye T. The London Fibromyalgia Epidemiology Study: the prevalence of fibromyalgia syndrome in London, Ontario. J Rheumatol 1999;26:1570–6.
4. Parsons CL, Dell J, Stanford EJ, Bullen M, Kahn BS, Waxell T, et al.. Increased prevalence of interstitial cystitis: previously unrecognized urologic and gynecologic cases identified using a new symptom questionnaire and intravesical potassium sensitivity. Urology 2002;60:573–8.
5. Zondervan KT, Yudkin PL, Vessey MP, Jenkinson CP, Dawes MG, Barlow DH, et al.. Chronic pelvic pain in the community—symptoms, investigations, and diagnoses. Am J Obstet Gynecol 2001;184:1149–55.
6. Clauw DJ, Schmidt M, Radulovic D, Singer A, Katz P, Bresette J. The relationship between fibromyalgia and interstitial cystitis. J Psychiatr Res 1997;31:125–31.
7. Giesecke J, Reed BD, Haefner HK, Giesecke T, Clauw DJ, Gracely RH. Quantitative sensory testing in vulvodynia patients reveals increased peripheral pressure pain sensitivity. Obstet Gynecol 2004;104:126–33.
8. Giesecke T, Gracely RH, Grant MAB, Nachemson A, Petzke F, Williams DA, et al.. Evidence of augmented central pain processing in idiopathic chronic low back pain. Arthritis Rheum 2004;50:613–23.
9. Johannesson U, de Boussard CN, Brodda Jansen G, Bohm-Starke N. Evidence of diffuse noxious inhibitory controls (DNIC) elicited by cold noxious stimulation in patients with provoked vestibulodynia. Pain 2007;130:31–9.
10. Pukall CF, Strigo IA, Binik YM, Amsel R, Khalife S, Bushnell MC. Neural correlates of painful genital touch in women with vulvar vestibulitis syndrome. Pain 2005;115:118–27.
11. Lautenbacher S, Rollman GB. Possible deficiencies of pain modulation in fibromyalgia. Clin J Pain 1997;13:189–96.
12. King CD, Wong F, Currie T, Mauderli AP, Fillingim RB, Riley JL 3rd. Deficiency in endogenous modulation of prolonged heat pain in patients with Irritable Bowel Syndrome and Temporomandibular Disorder. Pain 2009;143:172–8.
13. Meeus M, Nijs J, Van de Wauwer N, Toeback L, Truijen S. Diffuse noxious inhibitory control is delayed in chronic fatigue syndrome: an experimental study. Pain 2008;139:439–48.
14. Reed BD, Haefner HK, Harlow SD, Gorenflo DW, Sen A. Reliability and validity of self-reported symptoms for predicting vulvodynia. Obstet Gynecol 2006;108:906–13.
15. Burckhardt CS, Clark SR, Bennett RM. The fibromyalgia impact questionnaire: development and validation. J Rheumatol 1991;18:728–33.
16. Berry SH, Bogart LM, Pham C, Liu K, Nyberg L, Stoto M, et al.. Development, validation and testing of an epidemiological case definition of interstitial cystitis/painful bladder syndrome. J Urol 2010;183:1848–52.
17. Drossman DA, Corazziari E, Talley NJ, Thompson WG, Whitehead WE. Rome II: the functional gastrointestinal disorders: diagnosis, pathophysiology and treatment: a multinational consensus. McLean (VA): Degnon Associates; 2000.
18. Committee on Advancing Pain Research, Care, and Education. Relieving pain in America: a blueprint for transforming prevention, care, education, and research. Washington, DC: Institute of Medicine; 2011.
19. Nickel JC, Tripp DA, Pontari M, Moldwin R, Mayer R, Carr LK, 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;184:1358–63.
20. Whitehead WE, Palsson OS, Levy RR, Feld AD, Turner M, Von Korff M. Comorbidity in irritable bowel syndrome. Am J Gastroenterol 2007;102:2767–76.
21. Hoffmann RG, Kotchen JM, Kotchen TA, Cowley T, Dasgupta M, Cowley AW Jr. Temporomandibular disorders and associated clinical comorbidities. Clin J Pain 2011;27:268–74.
22. Gardella B, Porru D, Nappi RE, Dacc ò MD, Chiesa A, Spinillo A. Interstitial cystitis is associated with vulvodynia and sexual dysfunction—a case-control study. J Sex Med 2011;8:1726–34.
23. Aaron LA, Burke MM, Buchwald D. Overlapping conditions among patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder. Arch Intern Med 2000;160:221–7.
24. Rodriguez MA, Afari N, Buchwald DS, National Institute of Diabetes, Digestive, Kidney Diseases Working Group on Urological Chronic Pelvic Pain. Evidence for overlap between urological and nonurological unexplained clinical conditions. J Urol 2009;182:2123–31.
25. Levy RL, Whitehead WE, Von Korff MR, Feld AD. Intergenerational transmission of gastrointestinal illness behavior. Am J Gastroenterol 2000;95:451–6.
26. Warren JW, Clauw DJ, Wesselmann U, Langenberg PW, Howard FM, Morozov V. Sexuality and reproductive risk factors for interstitial cystitis/painful bladder syndrome in women. Urology 2011;77:570–5.
27. Harlow BL, Vazquez G, MacLehose RF, Erickson DJ, Oakes JM, Duval SJ. Self-reported vulvar pain characteristics and their association with clinically confirmed vestibulodynia. J Womens Health (Larchmt) 2009;18:1333–40.
28. Arnold LD, Bachmann GA, Rosen R, Rhoads GG. Assessment of vulvodynia symptoms in a sample of US women: a prevalence survey with a nested case control study. Am J Obstet Gynecol 2007;196:128.e1–6.
29. Carrico DJ, Sherer KL, Peters KM. The relationship of interstitial cystitis/painful bladder syndrome to vulvodynia. Urol Nurs 2009;29:233–8.
30. Zolnoun DA, Rohl J, Moore CG, Perinetti-Liebert C, Lamvu GM, Maixner W. Overlap between orofacial pain and vulvar vestibulitis syndrome. Clin J Pain 2008;24:187–91.
31. Arnold LD, Bachmann GA, Rosen R, Kelly S, Rhoads GG. Vulvodynia: characteristics and associations with comorbidities and quality of life. Obstet Gynecol 2006;107:617–24.
32. Wu EQ, Birnbaum H, Mareva M, Parece A, Huang Z, Mallett D, et al.. Interstitial cystitis: cost, treatment and co-morbidities in an employed population. Pharmacoeconomics 2006;24:55–65.
33. Warren JW, Howard FM, Cross RK, Good JL, Weissman MM, Wesselmann U, et al.. Antecedent nonbladder syndromes in case-control study of interstitial cystitis/painful bladder syndrome. Urology 2009;73:52–7.
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34. Warren JW, Wesselmann U, Morozov V, Langenberg PW. Numbers and types of nonbladder syndromes as risk factors for interstitial cystitis/painful bladder syndrome. Urology 2011;77:313–9.