Lifestyle Factors Associated with Abdominal Pain in Quiescent Inflammatory Bowel Disease

Abstract

Background

Lifestyle factors, including diet, exercise, substance use, and sexual activity, have been shown to influence risk of inflammation and complications in inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Little is known about their potential role in abdominal pain generation in IBD.

Aims

We performed this study to evaluate for relationships between lifestyle factors and abdominal pain in quiescent IBD (QP-IBD).

Methods

We performed a retrospective analysis utilizing data from our institution’s IBD Natural History Registry (January 1, 2017–December 31, 2022). Endoscopic evaluation, concurrent laboratory studies and surveys were completed by participants. Demographic and clinical data were also abstracted.

Results

We identified 177 consecutive patients with quiescent disease (105 females:72 males; 121 with CD:56 with UC) for participation in this study, 93 (52.5%) had QP-IBD. Compared to patients with quiescent IBD without pain (QNP-IBD, patients with QP-IBD exhibited no significant differences in IBD type, location, severity or complication rate. Patients with QP-IBD were more likely to have anxiety/depression (55.9% vs. 32.1%, p = 0.002) and to use antidepressants/anxiolytics (49.5% vs. 21.4%, p < 0.001). They were also less likely to engage in exercise at least three times per week (39.8% vs. 54.8%, p = 0.05) or participate in sexual activity at least monthly (53.8% vs. 69.1%, p = 0.04). On logistic regression analysis, antidepressant and/or anxiolytic use was independently associated with QP-IBD [2.72(1.32–5.62)], while monthly sexual activity was inversely associated [0.48(0.24–0.96)].

Conclusion

Lifestyle factors, including the lack of sexual activity and exercise, are significantly associated with QP-IBD. Further study is warranted to clarify the relationships between these factors and the development of abdominal pain in quiescent IBD.

Graphical Abstract

Introduction

Abdominal pain is common in inflammatory bowel disease (IBD), including both Crohn’s disease (CD) and ulcerative colitis (UC), even during periods of quiescence [1–3]. Previous reports indicate that up to two-thirds of patients with quiescent IBD experience abdominal pain [4]. This is important because this symptom is one of the major reasons individuals with IBD seek out medical attention [1, 3, 5]. Abdominal pain also exerts a significant impact on patient quality of life, and has been estimated to incur billions of dollars each year in health care costs and lost work hours in the United States alone [3, 6–13].

Abdominal pain in quiescent IBD can be particularly challenging to manage, in part because there are several potential contributors that need to be considered in this context. For example, age, female sex, corticosteroid use, and opioid use have all previously been associated with visceral hyperalgesia in IBD [4]. There is also evidence that some patients describing abdominal pain during periods of apparent remission actually exhibit persistent low-grade inflammation in the gut [2, 14–16]. Further studies have demonstrated that many of these patients have coincident psychiatric disorders, including anxiety, depression, and somatoform disorders, that may modulate the visceral sensory and pain experience [2, 8, 17]. Brain-gut disorders, including irritable bowel syndrome (IBS), are common and it is likely that some cases of abdominal pain in quiescent IBD are related to one of these conditions [18].

Additional potentially important contributors in this context are lifestyle factors. These include individual habits related to diet and nutritional status, exercise and physical activity, substance use and sexual activity, each of which have been evaluated in the setting of IBD [19]. Previous investigations have suggested that adherence to healthier lifestyle habits is independently associated with reduced likelihood of incidence or activity of IBD, even when considering other important potential contributors, such as genetic risk [20, 21]. For example, unhealthy dietary patterns (e.g., restricting healthy foods like fruits and vegetables even when asymptomatic and consuming diets rich in processed proteins or carbohydrates) and abnormal patient BMI (including being either underweight or obese) can have negative effects on treatment efficacy, the course of IBD and/or likelihood of experiencing IBD-associated symptoms [22–25]. Structured exercise programs have also previously been associated with several positive outcomes, including measures of disease activity in IBD and reduction in severity or frequency of at least some symptoms (e.g., fatigue), particularly in the setting of quiescent disease [26, 27]. Substance use has also been implicated as a potentially important variable in this context. Alcohol, tobacco, and narcotic use may increase the risk of flares and associated symptoms in IBD, including pain [28, 29]. To date, however, no studies have been undertaken to specifically evaluate the impact of lifestyle factors on the development of pain in quiescent IBD.

We performed this investigation to study the potential influence of several lifestyle factors on the presence of abdominal pain during quiescent IBD. Study participants underwent endoscopic evaluation to determine disease activity status. They also completed concomitant surveys designed to characterize their abdominal pain experience, as well as recent activities related to diet, exercise, sex, and substance use. We compared the lifestyle activities in patients with quiescent IBD who did and did not exhibit abdominal pain, anticipating that unhealthy lifestyle habits (e.g., little to no exercise, substance use) would be directly associated with abdominal pain in quiescent IBD.

Materials and Methods

Study Population

We performed a retrospective analysis using information derived from the Intestinal Diseases Natural History Database and Gastrointestinal Data Registry at our institution between 1/1/2017 and 12/31/2022. These databases include clinical and research information related to the encounters of patients with IBD receiving clinical management at a tertiary care referral hospital with a dedicated IBD center that cares for over 5000 patients with IBD. Written informed consent was obtained from each participant and all of this work was performed in accordance with the rules and regulations set forth by the local Institutional Review Board (STUDY0000934).

In order to be included in this study, participants had to be adults (i.e., greater than 17 years of age) and have an established diagnosis of CD or UC, based upon standard clinical criteria routinely used to identify IBD [30]. They also needed to have undergone an ileocolonoscopy and completed simultaneous surveys on abdominal pain experience (including the short inflammatory bowel disease questionnaire (SIBDQ) and Harvey-Bradshaw index (HBI) or simple clinical colitis activity index (SCCAI)), as well as surveys related to dietary patterns, exercise, sexual activity, and substance use (see below).

Patients with UC were excluded if they had undergone previous IBD-related colonic surgery. We decided to proceed in this fashion primarily because the most common IBD-related surgery for patients with UC is a total colectomy which (at least theoretically) has the potential to “cure” the patient of the original disease. Additionally, individuals who were pregnant, had colitis of indeterminate nature and/or a current diagnosis of a gastrointestinal infection, cancer, endometriosis, pancreatitis, symptomatic cholelithiasis or other potential extra-luminal causes of abdominal pain, were excluded from this study. Patients with CD were excluded if they had surgery within the previous 6 months and/or if they had an ostomy at the time of evaluation.

Definitions and Data Abstraction

Quiescent disease was defined as a lack of any endoscopic evidence of luminal inflammation (i.e., a Mayo endoscopy sub-score for UC or simple endoscopic score for Crohn’s (SES-CD) of zero, respectively). Presence of “significant inflammation” was defined as moderate to severe activity based upon findings during endoscopic evaluation (UC: using a Mayo endoscopy sub-score ranging from 0 to 3, with 0 = no disease (“quiescent”), 1 = mild disease, 2 = moderate disease, and 3 = severe disease; CD: using SES-CD scores of 7–15 for moderate disease and > 15 for severe disease) and histopathological evaluation (hematoxylin and eosin (H&E) sections were blindly assigned an inflammatory score on a scale of 0–3 by a trained pathologist specializing in digestive disease). Of note, all individuals included in this study had undergone previous endoscopic and radiologic testing and IBD location and type was based upon the findings of those tests. This information was used to make the most objective assessment of current gastrointestinal inflammatory status possible. To this end, all determinations about inflammatory state were based upon direct endoscopic evaluation of the mucosa and histologic assessment of tissue biopsies taken in areas of previously established disease activity.

In order to increase the rigor of the assessment of patient abdominal pain experience, our determination of the presence of abdominal pain in each case was based on responses to two separate questions answered on the day of ileocolonoscopy: (1) the fourth question in the SIBDQ (“How often over the past two weeks have you experienced abdominal pain?” where patients respond using a frequency-based inverse Likert scale, with 1 representing pain “all of the time” and 7 representing pain “none of the time”) and (2) the second item from the HBI which assess current severity of abdominal pain and includes potential responses of 0 (“no abdominal pain”), 1 (“mild”), 2 (“moderate”), and 3 (“severe”). For the purposes of this study, the presence of abdominal pain was defined as a numeric rating of < 6 on the SIBDQ pain score and a score of 1 or greater on the HBI pain score. Patients were asked to focus on abdominal pain experience unrelated to symptoms they may have experienced in the setting of their respective bowel preps. Additionally, no study participants had a history of or demonstrated objective evidence of extra-luminal causes of abdominal pain (including pancreatitis, symptomatic cholelithiasis, endometriosis) based upon the most recent laboratory and imaging studies or clinical evaluation.

Dietary behavior was assessed by asking study participants, “How many times per day do you normally eat?” (with potential responses including (a) less than one meal per day, (b) one meal a day, (c) two meals a day, (d) three meals a day, (e) more than three meals a day). We compared the proportion of study participants who reported three or more meals per day to those reporting consumption of less than three meals a day between the QP-IBD and QNP-IBD cohorts. Nutritional status was assessed by evaluating the mean body mass index (BMI, kg/m²) and serum albumin level (g/dL) of the two cohorts above. Incidence of BMI outside of the “normal” range (18.5–24.9 kg/m²) was also compared between these cohorts. Recent physical activity levels were evaluated by asking the question, “How many times per week do you exercise?” and “How long (in minutes) do you exercise per week?”. The proportions of individuals who reported exercising three or more times per week to those exercising less than three times per week were compared between patients with QP-IBD and QNP-IBD. The mean time engaged in exercise each week was also compared between these cohorts. Of note, we also compared the proportions of individuals who reported undertaking 150 min of exercise per week (the minimum amount of time for adults to exercise each week recommended by the Centers for Disease Control (cdc.gov)) in both of these cohorts, but there were only four total individuals [QP-IBD = 3 (3.2%) vs. QNP-IBD = 1 (1.2%), p = 0.62] who met this criterion, so we opted against reporting this particular analysis below. Sexual activity was evaluated based upon responses to the question, “In the past month, how many times have you been sexually active?” Participant responses were dichotomized to compare individuals reporting to have sex once or more in the past month to those reporting no sexual activity in the last month. Finally, substance use was evaluated using the following questions: (a) “Over the past week, have you smoked or vaped tobacco?”, (b) “Over the past week, how many alcoholic drinks have you consumed?”, (c) “Over the past week, have you used any of the following substances and, if so, how many times have you used them: (1) cannabis/marijuana, (2) cocaine, (3) methamphetamine, (4) heroin/non-prescription opioid?” As relatively few study participants reported use of cocaine, methamphetamine or heroin/non-prescription opioids, we combined all of them into the category described as “illicit substance use” and evaluated their use in aggregate. Finally, current prescription opioid use was also assessed. Responses were dichotomized based upon any reported use of a particular substance or no use at all.

In addition to the information outlined above, other clinical and demographic data was abstracted from the electronic medical record. Specifically, age, gender, IBD duration, IBD extent/location (e.g., organ involvement, using the Montreal classification system), disease complications (including intestinal stricture and intra-abdominal fistula), extra-intestinal manifestations (EIMs) (including inflammatory arthritides, IBD-associated dermatopathies (including pyoderma gangrenosum), erythema nodosum, uveitis, episcleritis, and primary sclerosing cholangitis), medication use (including antidepressant/anxiolytic, corticosteroid, mesalamine, immunomodulator (azathioprine, 6-mercaptopurine, and/or methotrexate) and biologic therapy (infliximab, adalimumab, certolizumab, golimumab, vedolizumab, and/or ustekinumab)), IBD surgery history, laboratory values (white blood cell count (WBC), sedimentation rate (ESR), C-reactive protein (CRP)), “other” pain medication use (acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), dicyclomine, and/or tricyclic agents) were abstracted. Presence of anxiety or depression symptoms was determined based upon responses to the hospital anxiety and depression scale (HADS) completed at the time of the clinical encounter, using anxiety or depression sub-scores of 8 or greater to indicate the clinically significant presence of each [31].

Statistical Analysis

Data was extracted and analyzed using GraphPad Prism version 8 (San Diego, CA) or R 4.2.0 (R Core Team (2022). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org.). Initially, summary statistics were computed for the whole study cohort and then for the following sub-cohorts: (1) patients with quiescent IBD with abdominal pain (hereafter referred to as “QP-IBD”) and (2) patients with quiescent IBD without abdominal pain (hereafter referred to as “QNP-IBD”). Bivariate analysis (e.g., two sample student’s t-test, chi-square test or Fisher’s exact test, as appropriate) were also performed to compare demographic and clinic variables for the QP-IBD and QNP-IBD sub-cohorts. A multivariable logistic regression model was then performed incorporating each significant variable (α = 0.05) identified during the bivariate analysis above, along with four other clinical variables (age, female sex, corticosteroid use, opioid use) that had previously been associated with visceral hyperalgesia in IBD [4], to examine the odds of developing abdominal pain in quiescent IBD. The outcome of interest in the logistic regression analysis was QP-IBD (as defined above). Values listed represent means ± standard error measurement (SEM), percentages or odds ratio (OR) with 95% confidence intervals (CI) unless indicated otherwise.

Results

Demographic and Clinical Characteristics

After evaluating consecutive patients who had undergone an ileocolonoscopy (for restaging of IBD and/or to evaluate gastrointestinal symptoms) and completed concurrent surveys to describe abdominal pain experience and lifestyle habits at our center, 177 total patients (105 females, 72 males) were found to have quiescent disease (i.e., Mayo endoscopy sub-score or SES-CD of zero and histopathologic inflammatory score of zero) (Table 1). In the total cohort, 121 individuals had CD [34.7% ileal CD (L1), 13.2% colonic CD (L2), 52.1% ileo-colonic CD (L3), 3.3% upper gastrointestinal (L4)]. Fifty-six patients had UC [5.4% had proctitis (E1), 26.8% left-sided UC (E2), 67.8% pan-UC (E3)].

Table 1.

Demographic and clinical characteristics of quiescent IBD patient cohorts

Variable	Cohort	Quiescent IBD with pain (QP-IBD)	Quiescent IBD without pain (QNP-IBD)	p value
Sample (% women)	177 (59.3%)	93 (56.2%)	84 (47.2%)	0.284
Age (years)	44.9±1.9	43.5±1.5	46.5±1.8	0.211
Disease type	CD-121 UC-56	69 24	52 32	0.105
Disease duration (years)	14.1±1.3	10.9±0.9	14.7±1.2	0.014
Stricturing (CD)	73	42 (60.9%)	31 (59.6%)	0.999
Non-perianal fstula(e) (CD)	34	18 (26.1%)	16 (30.8%)	0.683
EIM ever	92	52 (55.9%)	40 (47.6%)	0.294
SIBDQ	49.1±0.9	43.0±1.1	56.0±1.1	<0.0001
Harvey-Bradshaw index	5.3±0.3	6.5±0.4	4.0±0.4	<0.0001
Short clinical colitis activity Index	3.2±0.2	4.2±0.3	2.1±0.3	<0.0001
Laboratory studies
WBC (103 cells/mm3)	7.3±0.3	7.6±0.3	6.9±0.5	0.204
ESR (mm/hour)	17.5±1.8	19.6±2.5	13.4±1.7	0.100
CRP (mg/dL)	0.9±0.1	1.0±0.1	0.7±0.1	0.100
Active IBD medication use
Corticosteroid	15	9 (9.7%)	6 (7.1%)	0.599
Mesalamine	52	23 (24.7%)	29 (34.5%)	0.185
Immunomodulator	35	20 (21.5%)	15 (17.9%)	0.576
Biologic	100	55 (59.1%)	45 (53.6%)	0.544
Symptoms of anxiety/depression	79	52 (55.9%)	27 (32.1%)	0.002
Antidepressant/anxiolytic use	64	46 (49.5%)	18 (21.4%)	<0.001
Prior IBD-related surgery	58	32 (34.4%)	26 (31.0%)	0.635

EIM extra-intestinal manifestation, SIBDQ short infammatory bowel disease questionnaire, ESR sedimentation rate, CRPC-reactive protein

Quantitative parameters are expressed as mean±SEM and qualitative parameters are shown as n (%)

In the total cohort, 93 patients (52.5%) were found to have QP-IBD. CD and UC exhibited statistically similar rates of QP-IBD (57.0% vs. 42.9% respectively, p = 0.11). Patients with QP-IBD exhibited a shorter mean disease duration compared to their pain-free quiescent counterparts (10.9 years vs. 14.7 years, p = 0.014). However, age (43.5 years vs. 46.5 years, p = 0.211), female sex (56.2% vs. 47.2%, p = 0.284), disease distribution [CD: L1 34.8% vs. 34.6%, L2 13.0% vs. 13.5%, L3 52.2% vs. 51.9% (p = 0.998); UC: E1 8.3% vs. 3.1%, E2 37.5% vs. 18.8%, E3 54.2% vs. 78.1% (p = 0.161)] and incidence of disease complications in CD such as stricturing (60.9% vs. 59.6%, p = 0.999) and intra-abdominal fistulae (26.1% vs. 30.8%, p = 0.634), were similar between the QP-IBD and QNP-IBD sub-cohorts respectively. Incidence of extra-intestinal manifestations (EIMs) of IBD were also statistically similar (55.9% vs. 47.6%, p = 0.294). Additionally, the rates of previous IBD-related surgery in patients with CD were very similar (34.4% vs. 31.0%, p = 0.635). Patients with QP-IBD exhibited a lower mean IBD-associated quality of life (SIBDQ) (43.0 vs. 56.0, p < 0.001) and higher disease activity scores (HBI: 6.5 vs. 4.0, p < 0.001; SCCAI: 4.2 vs. 2.1, p < 0.001). Patients with QP-IBD were also more likely to have significant symptoms of anxiety and/or depression (65.8% vs. 34.2%, p = 0.002), and had a higher rate of antidepressant/anxiolytic use (49.5% vs. 21.4%, p < 0.001). Inflammatory marker values (including WBC (10³ cells/mm³) (7.6 vs. 6.9, p = 0.204), ESR (mm/hour) (19.6 vs. 13.4, p = 0.100), and CRP (mg/dL) (1.0 vs. 0.7, p = 0.100)) were similar between the cohorts. Current corticosteroid (9.7% vs. 7.1%, p = 0.599), mesalamine (24.7% vs. 34.9%, p = 0.185), immunomodulator (21.5% vs. 17.9%, p = 0.576), and biologic (59.1% vs. 53.6%, p = 0.544) use were each statistically similar between these cohorts. No other overt differences in demographics or clinical characteristics were identified.

Lifestyle Factors in the Quiescent IBD Cohorts

Dietary Behavior and Nutritional Status

Mean BMI (kg/m²) (29.1 vs. 27.9, p = 0.321) and mean albumin (g/dL) (4.1 vs. 4.1, p = 0.981) were not significantly different between the QP-IBD and QNP-IBD cohorts (Table 2). The proportions of each cohort that had an abnormal BMI (i.e., lower than or higher than a BMI of 18.5–24.9 kg/m²) were also statistically similar (65.6% vs. 57.1%, p = 0.28). To evaluate dietary behavior, we asked study participants, “How many times per day do you normally eat?”. Patients with QP-IBD and QNP-IBD demonstrated statistically similar proportions of participants that were eating at least three meals each day (44.1% vs. 51.2, p = 0.369).

Table 2.

Lifestyle factors in the quiescent IBD patient cohorts

Variable	Cohort	Quiescent IBD with pain (QP-IBD)	Quiescent IBD without pain (QNP-IBD)	p value
Dietary and nutritional assessment
Eating 3+meals per day	84	41 (44.1%)	43 (51.2%)	0.127
BMI	28.5±0.6	29.1±0.9	27.9±0.8	0.321
Abnormal BMI	109	61 (65.6%)	48 (57.1%)	0.280
Albumin (g/dL)	4.1±0.1	4.1±0.1	4.1±0.2	0.981
Exercise
Exercise sessions per week	2.4±0.2	2.1±0.2	2.7±0.3	0.108
Time exercising per week (minutes)	28.3±4.8	30.1±8.4	26.4±3.7	0.700
Exercising 3+times per week	82	36 (38.7%)	46 (54.8%)	0.036
Sexual activity
Number of times had sex last month	2.6±0.3	2.3±0.4	2.9±0.5	0.363
Sexually active 1+time last month	108	50 (53.7%)	58 (69.0%)	0.045
Active substance/pain medication use
Tobacco	17	10 (10.8%)	7 (8.3%)	0.620
Alcohol	58	25 (26.9%)	33 (39.3%)	0.108
Cannabis	13	9 (9.7%)	4 (4.8%)	0.257
Opioid	20	11 (11.8%)	9 (10.7%)	0.999
Illicit substances	14	4 (4.3%)	10 (11.9%)	0.092
Other pain meds	76	45 (48.4%)	31 (36.9%)	0.138

Quantitative parameters are expressed as mean±SEM and qualitative parameters are shown as n (%)

Exercise

To assess recent physical activity, we asked participants, “How many times per week do you exercise?” and “How much time (in minutes) do you spend exercising per week?”. Patients with QP-IBD were less likely to report exercising three times or more per week (39.8% vs. 54.8%, p = 0.05). However, the two cohorts reported exercising for statistically similar mean numbers of sessions per week (2.3 vs. 2.9, p = 0.108) and total time per week (30.1 min vs. 26.4 min, p = 0.700).

Sexual Activity

We asked study participants, “In the past month, how many times have you been sexually active?” While the QP-IBD and QNP-IBD cohorts reported having sex a similar number of times over the past month (2.3 vs. 2.9 times per month, p = 0.363), patients with QP-IBD were less likely to have sex at least once per month (53.8% vs. 69.1%, p = 0.045).

Substance (and Pain Medication) Use

Relative rates of any alcohol (26.9% vs. 39.3, p = 0.108), tobacco (10.8% vs. 8.4%, p = 0.620), cannabis (9.7% vs. 4.8%, p = 0.257), and illicit substance use (including cocaine, methamphetamine, and heroin/non-prescription opioid) (4.3% vs. 11.9%, p = 0.092) were not statistically different between the QP-IBD and QNP-IBD cohorts. Current (prescribed) opioid use (11.8% vs. 10.7%, p = 0.999) and other pain medication use (including acetaminophen, NSAIDs, tricyclic antidepressants, and dicyclomine) (48.4% vs. 36.9%, p = 0.138) were similar between the cohorts.

Multivariable Analysis

In order to evaluate for independent associations with the QP-IBD phenotype, we performed a multivariable logistic regression analysis including the whole quiescent IBD cohort (n = 177). We included nine separate clinical variables that were found to be significantly directly or inversely associated with the QP-IBD cohort on the bivariate analyses above (disease duration, concomitant symptoms of anxiety and/or depression, antidepressant/anxiolytic use, exercise (three times or more per week), and sexual activity (at least once a month)) or had been associated with this cohort on previous analyses (age, female sex, corticosteroid use, opioid use). In this analysis, the QP-IBD cohort was independently associated with antidepressant/anxiolytic use and inversely associated with having sex at least once a month (Table 3).

Table 3.

Multivariable analysis, associations with abdominal pain in quiescent IBD

Variable	Odds ratio (95% confdence interval)	p value
Age	1.76 (0.45–6.87)	0.414
Disease duration	0.99 (0.929–1.00)	0.065
Female sex	1.11 (0.55–2.24)	0.780
Anxiety/depression symptoms	1.92 (0.97–3.80)	0.060
Antidepressant and/or anxiolytic use	2.72 (1.32–5.62)	0.007
Corticosteroid use	1.62 (0.46–5.04)	0.494
Opioid use	1.03 (0.37–2.92)	0.952
Exercise at least three times per week	0.80 (0.40–1.58)	0.515
Sex at least once per month	0.48 (0.24–0.96)	0.039

Discussion

We demonstrated that abdominal pain in quiescent IBD (QP-IBD) was independently inversely associated with sexual activity (at least on a monthly basis). We also found (on bivariate analysis) that patients with QP-IBD were less likely to engage in exercise (at least on a triweekly or more frequent basis). We did not find an association between QP-IBD and any of the dietary/nutritional parameters or substance use inquiries that we made. This study again also highlighted the fact that abdominal pain is very common in quiescent IBD, including both CD and UC. The incidence of abdominal pain in this quiescent study cohort (including both CD and UC) was similar to that described in our previous study of abdominal pain in quiescent IBD [4]. As demonstrated in the previous study, we also found no statistically significant differences in IBD type, location, complications (including EIM’s, strictures or fistulae), surgical history or objective measures of inflammatory activity. Patients with QP-IBD were also more likely to exhibit an anxious or depressed state, and increased likelihood of using antidepressants or anxiolytics. Unlike the previous study, female sex, current opioid and corticosteroid use were not associated with QP-IBD (though opioid prescriptions over the past year were).

This is the first study to specifically evaluate for potential relationship(s) between lifestyle factors and abdominal pain in quiescent inflammatory bowel disease. It is also the first study to demonstrate a potential association between sexual activity, exercise and this particular patient cohort. Considering the design of this study, we cannot establish any cause and effect relationship(s) with these associations. Thus, while it is possible that reduced exercise and/or sexual activity could have contributed to patient pain experience, it is also possible that patients with QP-IBD were simply less likely to engage in these activities because of their pain.

Sexual activity has been studied in IBD as well. Several previous investigations have demonstrated that sexual dysfunction is more common in patients with IBD, as a result of disease activity, medications, surgery, and/or psychosocial factors related to the disease itself [32, 33]. However, we are not aware of previous studies that have evaluated the impact of sexual activity itself on IBD activity and/or the incidence of its associated symptoms (including abdominal pain). This is an interesting possibility, as several previous animal and human studies have demonstrated that sexual arousal, stimulation and/or activity can lead to analgesia and/or development of increased thresholds of somatosensory pain perception, presumably through the release of endorphins and endogenous opioids. We are not aware of any previously published work that has specifically evaluated the potential influence of sexual activity on abdominal (or visceral) pain experience. However, it is possible that individuals who are more frequently engaged in sexual activity may be at reduced risk of developing abdominal pain and/or, if they do, may experience less severe pain. This is a worthwhile consideration for future studies to evaluate for.

The impact of exercise on IBD has been studied as well and some previous investigations have included assessments of abdominal pain. Unfortunately, these studies have been difficult to interpret due to differences in exercise type, study methodology, and/or outcomes. For example, a survey of 918 patients with IBD undertaken in the United Kingdom found that 607 (66%) individuals engaged in some form of exercise on at least a weekly basis. Of the patients that exercised, 72% reported feeling generally better (including 12% who reported improvement in one or more IBD-associated symptoms) as a result of the exercise. However, 23% of respondents reported that exercise made them feel worse, including 17% who described worsening abdominal pain [34]. In a separate prospective study of patients with IBD in clinical remission, those who performed at least one hour of yoga daily over an 8 week span reported a reduced frequency of several symptoms, including “intestinal colic pain” [35].

Similar to our previous study, we also demonstrated that differences in pain reporting in patients with quiescent IBD are not related to disease type, location, activity, IBD-related complications (including the presence of strictures, fistulae, and/or extra-intestinal manifestations) or differential use of analgesics or other pain-modifying substances (e.g., alcohol, cannabis, opioids). These findings again suggest that abdominal pain perception in quiescent IBD is influenced by other factors. One recurrent variable that appears to be playing a role are symptoms related to anxiety and/or depression. Several previous studies have demonstrated a potential linkage between these symptoms and the development of pain in IBD during periods of remission [2, 4, 8, 17]. Indeed, we found that same association again in the present study. However, this factor does not explain all abdominal pain in this context, as approximately half of the QP-IBD in this study demonstrated no concurrent evidence of these disorders or significant anxious or depressed symptoms. Importantly, it should also be noted that antidepressants and/or anxiolytics are frequently prescribed (at least in part) to assist with pain management. Thus, these medications may be an indicator of the presence of pain rather than coincident mood disorders in some patients. Accordingly, it is certainly possible that lifestyle factors are potentiating abdominal pain for some of these individuals.

There are several potential limitations to this study. First, this was a relatively small investigation, which evaluated even smaller subtypes of IBD (e.g., CD and UC). Therefore, it may have been underpowered to evaluate for some clinical relationships. For example, previous studies have indicated that being underweight or obese may increase risk of developing CD but not necessarily UC [22, 23]. It is possible that an abnormal BMI could also impart a differential impact on pain experience. Secondly, this study was undertaken in a single tertiary care referral center, and so these findings may not be relevant to all patients with IBD. Third, the retrospective design of this study increases the likelihood of recall or selection bias. This study design is also not a reliable way to evaluate for potential cause and effect relationships. Fourth, we did not have reliable data regarding timing of the initial diagnosis of relevant conditions (e.g., anxiety and/or depression) this may have limited our ability to evaluate important potential clinical relationships. Fifth, we did not have consistent results related to other testing modalities that could have provided a more comprehensive assessment of luminal and extra-luminal intestinal inflammatory status (such as stool-based markers of intestinal inflammation (e.g., fecal calprotectin) or abdominal/luminal imaging studies (e.g., CT or MR enterography). As previously reviewed, this is relevant due to the possibility of missing heretofore unrecognized deep small bowel or mesentery-based inflammation, which could be contributing to patient symptoms, including abdominal pain [36–38]. Beyond this, we were also unable to definitively rule out some potential causes or modifiers of abdominal pain, including small bowel bacterial overgrowth, food intolerances, and intra-abdominal adhesions. We also excluded patients with UC who had undergone previous IBD-related surgery, potentially limiting some of the more severe cases in this analysis. Additionally, it should be noted that the lifestyle questions used have not been specifically validated in the setting of IBD. Finally, we were not able to reliably include other potentially impactful lifestyle factors in our analysis, including sleep hygiene and stress, patient relationship status, or specific characteristics of the factors we did attempt to address, including specific approaches to diet and exercise. For example, use of a low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet has been associated with reduced IBD-related symptoms, including abdominal pain [39]. It would be helpful to evaluate the influence of this diet on the likelihood of developing and/or course of QP-IBD.

This investigation is relatively novel, though, because it demonstrated a heretofore unrecognized association between abdominal pain in quiescent IBD and reduced frequency of sexual activity and exercise. In order to verify these findings and to further clarify the potential meaning of these associations, additional larger scale human studies investigating these variables in more depth are warranted. This study also demonstrated (again) an association between symptoms of anxiety and depression and abdominal pain in quiescent IBD. This reinforces the importance of integrating psychiatric care into the regular management of patients with IBD. Finally, the results of this investigation highlight the ongoing need to more carefully investigate contributors to abdominal pain in this setting. Patients with abdominal pain in quiescent IBD have been linked to several drivers of abdominal pain (as outlined above), but human visceral pain perception continues to pose a uniquely challenging phenomenon to understand and manage. As such, there remains a need to identify and develop novel approaches to safely and effectively care for this patient population. Lifestyle factors may be very important in regard to the development and management of abdominal pain in IBD and further studies are needed to clarify their potential in this setting.

Data availability

Not applicable.