https://orcid.org/0000-0003-2079-0081
Abstract
The abdominal pain common in inflammatory bowel disease [IBD] patients is traditionally associated with inflammation but may persist during clinical remission. Central sensitization [CS] has not previously been explored in these patients. This study aimed to determine the epidemiology of pain in IBD patients and to specify pain characteristics with particular attention to CS.
This cross-sectional study included 200 patients; 67% had Crohn’s disease [CD]. Pain was assessed using the McGill questionnaire, using the Douleur Neuropathique 4 [DN4] questionnaire and by clinical examination. Its impacts on quality of life, depression and anxiety were also assessed.
Three-quarters of IBD patients complained of pain, including intermittent pain attacks, 62% reported abdominal pain and 17.5% had CS. The prevalence of pain [83.6% vs 59.1%; p < 0.001] and abdominal pain [68.7% vs 48.5%; p = 0.006] was higher in CD patients than in ulcerative colitis [UC] patients. Multivariate analysis confirmed that age [p = 0.02], sex [female] [p = 0.004] and CD [p = 0.005] were independent risk factors for pain. Pain intensity was greater in the case of CS (6 [5–3] vs 3 [1.5–5], p < 0.003) which significantly impaired quality of life [p < 0.003] compared with pain without CS.
The prevalence of pain was high in IBD patients [≈75%] and higher in CD patients. Significant impacts on quality of life were confirmed. More than 25% of patients with abdominal pain described CS as responsible for more severe pain and worsened quality of life.
NCT04488146
1. Introduction
Abdominal pain is common in patients with inflammatory bowel disease [IBD].1 In addition to abdominal pain, some pain may result from extra-intestinal manifestations of IBD.2–4 Although abdominal pain is conventionally attributed to inflammation, IBD patients also complain of functional abdominal pain with various causes.5 About 20–40% of patients in complete clinical and endoscopic remission continue to experience chronic pain.6 Central sensitization, defined as ‘increased responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input’ [http://www.iasp-pain.org], can occur in patients with chronic visceral conditions, leading to pain now categorized as nociplastic pain.7–9 Therefore, when examining an IBD patient with abdominal pain, besides potential causative complications of IBD, such as inflammation or intestinal stenosis, it is important to look for associated causes of both peripheral origin [including visceral hypersensitivity, bacterial proliferation and intestinal dysmotility] and of central origin responsible for neurobiological and psychosocial changes.5 Opioid-induced hyperalgesia is another potential central source of abdominal pain, as more and more IBD patients are being treated in the long term with opioids.10
Repetitive inflammatory episodes during IBD may result in prolonged hypersensitivity of peripheral nociceptors and in higher pain processing areas of the spinal cord and/or supra-spinal nervous system, which may persist after inflammation has resolved.5,11 These pathophysiological changes may result in central sensitization7,8,12 We have reported that IBD was an independent risk factor for chronic postsurgical pain with clinical presentations of neuropathic pain after laparoscopic colectomy despite the minimal invasiveness of the surgical approach.13 In IBD patients, nociplastic pain may share multiple pathophysiological mechanisms and clinical presentations of central sensitization with neuropathic pain.8,14
Potentially severe and debilitating pain is a common symptom of IBD. Aside from disease-modifying agents, pain treatments remain sparse and understudied. This is partly because of the complexity of pain aetiologies and the psychological dysfunction associated with the chronicity of the disease.4–6,15 Knowledge of the characteristics of pain in IBD patients and their potential aetiologies may be useful in guiding proper diagnosis and individualizing the treatment of pain in these patients. A few studies on the prevalence and characteristics of pain in large cohorts of IBD patients have been reported,1 but assessments of chronic pain and more specifically those focusing on hyperalgesic and central sensitization characteristics of pain are scant.6 In this setting, by using a consecutive IBD cohort attending our specialist IBD outpatient clinic, this cross-sectional study aimed to determine the epidemiology of pain in patients with IBD and to specify the characteristics of their pain [location, temporal characteristics, acute vs chronic, sensory characteristics, central sensitization characteristics and hyperalgesia], and their impact on quality of life, depression and anxiety. The originality of our study was that the pain assessment used a questionnaire combined with a clinical examination and focused on the occurrence of clinical presentations of central sensitization in patients with abdominal pain and its consequences.
2. Materials and Methods
This monocentric prospective cross-sectional study was approved by the Institutional Ethics Committee of the Centre Hospitalier Universitaire de Liège [Liège, Belgium, Chair: Prof. V. Seutin, No. 2020/289] on November 2, 2020 and registered with Clinical Trials under NCT04488146. After obtaining their written informed consent, 200 consecutive IBD patients consulting with one gastroenterologist [E.L.] in our IBD outpatient clinic were finally included in this study.
2.1. Patient recruitment
This study was conducted between November 2020 and April 2021 on patients with confirmed Crohn’s disease [CD] and ulcerative colitis [UC] aged 18 years and older and with adequate French language proficiency to fill out questionnaires. The same gastroenterologist [E.L.] ascertained current disease, medical history and current medications. Disease activity was assessed using the Harvey–Bradshaw Index [HBI]16 and Partial Mayo Scoring Index Assessment [PRO2]17 for CD, and Mayo score18 and PRO219 for UC at the time of the interview. Active disease was attested when the HBI exceeded 4 in CD patients and when the Partial Mayo Scoring Index exceeded 2 in UC patients.20
2.2. Measurements
The primary endpoint was prevalence of abdominal pain with clinical presentation of central sensitization in IBD patients. Central sensitization was defined as pain with cutaneous hyperalgesia, sensorial experience and pain descriptors [electric shock, tingling, burning, painful feeling of cold] conventionally associated with neuropathic pain, and a DN4 [Douleur Neuropathique 4 questions]21 score exceeding 4.
The secondary endpoints were prevalence of pain, chronic pain, abdominal and extra-intestinal pain, and impact of pain on psychological co-morbidities and patient well-being in IBD patients.
These assessments were obtained from questionnaires filled out by patients and a clinical examination.
2.3. Questionnaires used
All the patients completed a survey with the assistance of one of two investigators [P.Y.H., J.F.] to limit bias when filling out the questionnaires. The survey included a questionnaire to determine the prevalence of pain, its location and its temporal characteristics. Pain intensity was assessed using a 0–10-cm visual analogue scale [VAS]. Chronic pain was defined as a pain lasting for more than 3 months.22 Sensory characteristics of pain and the occurrence of hyperalgesia were assessed using a questionnaire combining the short French version of the McGill questionnaire23 and the DN4.21 Associated psychological co-morbidities [anxiety and depression] were screened with the Hospital Anxiety and Depression [HAD] Scale24 previously used in IBD populations.25 The impact on the Health-Related Quality of Life [HRQoL] was assessed with the questionnaire used by Zeitz et al.1,26
2.4. Clinical examination
The survey was completed by a clinical examination of the abdomen performed by the same two investigators [P.Y.H., J.F.]. This included inspection, auscultation, palpation and percussion of the nine abdominal areas. Hypo-aesthesia was sought using a light touch with a 0.07-g Von Frey filament [Tactile sensory evaluators, Baseline Evaluation Instruments; Fabrication Enterprises Inc.] and standardized pinprick. Hyperalgesia, which heightened sensitivity to a painful stimulus, was tested using a standardized pinprick and allodynia, which is pain caused by a stimulus that normally does not elicit pain, was also sought using rubs with a 300-g Von Frey filament. The presence of hypo-aesthesia, hyperalgesia or allodynia was determined by referring to an area without pain and with normal tenderness.
2.5. Statistics
The normality of the distribution of quantitative variables was investigated graphically using histograms and quantile–quantile plots and tested using the Shapiro–Wilk test. Quantitative variables were expressed as mean ± SD, or median [interquartile range, IQR] when appropriate. Qualitative data were expressed as counts [per cent]. Quantitative variables were compared between groups using Student’s t test when normally distributed and using the Mann–Whitney U test for non-parametric data. The chi-square test or Fisher test were used to compare qualitative variables when appropriate.
A multivariate logistic regression was used to determine independent variables associated with pain. All variables that in the univariate analysis were associated with the dependent variable [i.e. pain] at p ≤ 0.05 were inserted into the logistic regression model. Odds ratios [OR], adjusted OR [aOR] and their 95% confidence intervals were calculated for these variables. Since active disease was defined using scales including pain as one of the items, this variable was not tested in these univariate and multivariate analyses.
A multivariate logistic regression was also used to determine independent variables associated with central sensitization in the population of patients with abdominal pain. All variables that in the univariate analysis were associated with the dependent variable [i.e. central sensitization] at p ≤ 0.05 or less were inserted into the logistic regression model.
No data were available for the prevalence of central sensitization in IBD patients with abdominal pain. We therefore hypothesized that 25% of IBD patients complaining of abdominal pain had clinical presentations of central sensitization. We had previously found that 25–30% of IBD patients complained of chronic postsurgical pain with symptoms of central sensitization after laparoscopic colectomy.13 For a reported prevalence of abdominal pain of 75% in IBD patients, the appropriate sample size for determining the hypothesized frequency of central sensitization in our pain population with a confidence limit of 5% and a confidence level of 95% was 120 patients with abdominal pain. We therefore decided to recruit 200 patients.
A p value of <0.05 was considered statistically significant. The method of Benjamini and Hochberg was used to adjust p values for multiple comparisons between patients with and without pain, and patients with and without central sensitization.27 An adjusted p value <0.05 was considered statistically significant. Only observed data were analysed. Data were analysed using the R 4.0.2 software [R Core Team, 2014].
3. Results
In total, 246 patients were screened for study eligibility. Forty-four patients declined to take part and two were excluded because of difficulty filling out the questionnaires or inconsistency in their responses. Two hundred patients were included in the final analysis.
3.1. Patient characteristics
Sixty-seven per cent of our patients had CD. HBI and PRO2 for CD were respectively 6 [3–8] and 10 [5–16]. Partial Mayo Scoring Index Assessments for UC Activity and PRO2 for UC were 2 [0.5–4] and 1 [0–2.5]. Characteristics of patients with CD and UC are presented in Table 1. Patients with CD were significantly lighter [p = 0.05] and shorter [p = 0.005], were more often cigarette smokers [p < 0.001], had more extra-intestinal manifestations [p = 0.03], had more often undergone surgery for IBD, and undertook less physical activity [p = 0.02] than the UC patients. More CD patients than UC patients presented with active disease at the time of the interview [p < 0.001].
Patient characteristics by IBD disorder
| All | Crohn’s disease | Ulcerative colitis | p | |
|---|---|---|---|---|
| N | 200 | 134 [67%] | 66 [33%] | |
| Age | 44.6 [19–87] | 44.7 [19–87] | 44.3 [19–75] | 0.92 |
| Sex male [%] | 93 [46.5%] | 59 [44%] | 34 [51.5%] | 0.32 |
| Weight [kg] | 72 ± 15.3 | 70.7 ± 15.5 | 74.6 ± 14.6 | 0.05 |
| Height [cm] | 170 ± 9 | 169 ± 9 | 173 ± 9 | 0.005 |
| BMI [kg/m2] | 24 [21.2–27.1] | 23.8 [20.9–27.2] | 24.6 [22.1–27] | 0.26 |
| Weight gain during the last 3 months | 62 [31%] | 41 [30.6%] | 21 [31.8%] | 0.86 |
| Weight loss during the last 3 months | 51 [25.5%] | 38 [28.4%] | 13 [19.7%] | 0.19 |
| Smoking | 48 [24%] | 45 [33.6%] | 3 [4.5%] | <0.001 |
| Alcohol > 10 U/week | 26 [13%] | 14 [10.4%] | 12 [18.2%] | 0.13 |
| Duration of IBD | 13.5 [7–22.2] | 13.5 [8–23] | 13.5 [6–20] | 0.33 |
| Extra-intestinal manifestation | 92 [46%] | 69 [51.5%] | 23 [34.8%] | 0.03 |
| Corticosteroids | 43 [21.5%] | 24 [17.9%] | 19 [28.8%] | 0.08 |
| Anti-TNFα or immunomodulators | 164 [82%] | 113 [84.3%] | 51 [77.3%] | 0.22 |
| Surgery for IBD | 52 [26%] | 49 [36.6%] | 3 [4.5%] | <0.001 |
| Physical activity | 101 [50.5%] | 60 [44.8%] | 41 [62.1%] | 0.02 |
| Pain [any type] | 151 [75.5%] | 112 [83.6%] | 39 [59.1%] | <0.001 |
| Abdominal pain | 124 [62%] | 92 [68.7%] | 32 [48.5%] | 0.006 |
| Central sensitization | 35 [17.5%] | 28 [20.9] | 7 [10.6] | 0.07 |
| Active disease | 103 [56.5%] | 85 [63.4%] | 17 [24.2%] | p < 0.001 |
| All | Crohn’s disease | Ulcerative colitis | p | |
|---|---|---|---|---|
| N | 200 | 134 [67%] | 66 [33%] | |
| Age | 44.6 [19–87] | 44.7 [19–87] | 44.3 [19–75] | 0.92 |
| Sex male [%] | 93 [46.5%] | 59 [44%] | 34 [51.5%] | 0.32 |
| Weight [kg] | 72 ± 15.3 | 70.7 ± 15.5 | 74.6 ± 14.6 | 0.05 |
| Height [cm] | 170 ± 9 | 169 ± 9 | 173 ± 9 | 0.005 |
| BMI [kg/m2] | 24 [21.2–27.1] | 23.8 [20.9–27.2] | 24.6 [22.1–27] | 0.26 |
| Weight gain during the last 3 months | 62 [31%] | 41 [30.6%] | 21 [31.8%] | 0.86 |
| Weight loss during the last 3 months | 51 [25.5%] | 38 [28.4%] | 13 [19.7%] | 0.19 |
| Smoking | 48 [24%] | 45 [33.6%] | 3 [4.5%] | <0.001 |
| Alcohol > 10 U/week | 26 [13%] | 14 [10.4%] | 12 [18.2%] | 0.13 |
| Duration of IBD | 13.5 [7–22.2] | 13.5 [8–23] | 13.5 [6–20] | 0.33 |
| Extra-intestinal manifestation | 92 [46%] | 69 [51.5%] | 23 [34.8%] | 0.03 |
| Corticosteroids | 43 [21.5%] | 24 [17.9%] | 19 [28.8%] | 0.08 |
| Anti-TNFα or immunomodulators | 164 [82%] | 113 [84.3%] | 51 [77.3%] | 0.22 |
| Surgery for IBD | 52 [26%] | 49 [36.6%] | 3 [4.5%] | <0.001 |
| Physical activity | 101 [50.5%] | 60 [44.8%] | 41 [62.1%] | 0.02 |
| Pain [any type] | 151 [75.5%] | 112 [83.6%] | 39 [59.1%] | <0.001 |
| Abdominal pain | 124 [62%] | 92 [68.7%] | 32 [48.5%] | 0.006 |
| Central sensitization | 35 [17.5%] | 28 [20.9] | 7 [10.6] | 0.07 |
| Active disease | 103 [56.5%] | 85 [63.4%] | 17 [24.2%] | p < 0.001 |
Data are mean [range] for age, number [%], mean ± SD, or median [IQR]. IBD = inflammatory bowel disease; BMI = body mass index; TNF = tumour necrosis factor. Central sensitization was defined as pain with cutaneous hyperalgesia, sensorial experience of pain and pain descriptors of neuropathic pain, and a DN4 score [Douleur Neuropathique 4 questions]21 >4. Active disease was defined as Harvey–Bradshaw Index16 >4 for CD patients and partial Mayo score19 >2 for UC patients.
Patient characteristics by IBD disorder
| All | Crohn’s disease | Ulcerative colitis | p | |
|---|---|---|---|---|
| N | 200 | 134 [67%] | 66 [33%] | |
| Age | 44.6 [19–87] | 44.7 [19–87] | 44.3 [19–75] | 0.92 |
| Sex male [%] | 93 [46.5%] | 59 [44%] | 34 [51.5%] | 0.32 |
| Weight [kg] | 72 ± 15.3 | 70.7 ± 15.5 | 74.6 ± 14.6 | 0.05 |
| Height [cm] | 170 ± 9 | 169 ± 9 | 173 ± 9 | 0.005 |
| BMI [kg/m2] | 24 [21.2–27.1] | 23.8 [20.9–27.2] | 24.6 [22.1–27] | 0.26 |
| Weight gain during the last 3 months | 62 [31%] | 41 [30.6%] | 21 [31.8%] | 0.86 |
| Weight loss during the last 3 months | 51 [25.5%] | 38 [28.4%] | 13 [19.7%] | 0.19 |
| Smoking | 48 [24%] | 45 [33.6%] | 3 [4.5%] | <0.001 |
| Alcohol > 10 U/week | 26 [13%] | 14 [10.4%] | 12 [18.2%] | 0.13 |
| Duration of IBD | 13.5 [7–22.2] | 13.5 [8–23] | 13.5 [6–20] | 0.33 |
| Extra-intestinal manifestation | 92 [46%] | 69 [51.5%] | 23 [34.8%] | 0.03 |
| Corticosteroids | 43 [21.5%] | 24 [17.9%] | 19 [28.8%] | 0.08 |
| Anti-TNFα or immunomodulators | 164 [82%] | 113 [84.3%] | 51 [77.3%] | 0.22 |
| Surgery for IBD | 52 [26%] | 49 [36.6%] | 3 [4.5%] | <0.001 |
| Physical activity | 101 [50.5%] | 60 [44.8%] | 41 [62.1%] | 0.02 |
| Pain [any type] | 151 [75.5%] | 112 [83.6%] | 39 [59.1%] | <0.001 |
| Abdominal pain | 124 [62%] | 92 [68.7%] | 32 [48.5%] | 0.006 |
| Central sensitization | 35 [17.5%] | 28 [20.9] | 7 [10.6] | 0.07 |
| Active disease | 103 [56.5%] | 85 [63.4%] | 17 [24.2%] | p < 0.001 |
| All | Crohn’s disease | Ulcerative colitis | p | |
|---|---|---|---|---|
| N | 200 | 134 [67%] | 66 [33%] | |
| Age | 44.6 [19–87] | 44.7 [19–87] | 44.3 [19–75] | 0.92 |
| Sex male [%] | 93 [46.5%] | 59 [44%] | 34 [51.5%] | 0.32 |
| Weight [kg] | 72 ± 15.3 | 70.7 ± 15.5 | 74.6 ± 14.6 | 0.05 |
| Height [cm] | 170 ± 9 | 169 ± 9 | 173 ± 9 | 0.005 |
| BMI [kg/m2] | 24 [21.2–27.1] | 23.8 [20.9–27.2] | 24.6 [22.1–27] | 0.26 |
| Weight gain during the last 3 months | 62 [31%] | 41 [30.6%] | 21 [31.8%] | 0.86 |
| Weight loss during the last 3 months | 51 [25.5%] | 38 [28.4%] | 13 [19.7%] | 0.19 |
| Smoking | 48 [24%] | 45 [33.6%] | 3 [4.5%] | <0.001 |
| Alcohol > 10 U/week | 26 [13%] | 14 [10.4%] | 12 [18.2%] | 0.13 |
| Duration of IBD | 13.5 [7–22.2] | 13.5 [8–23] | 13.5 [6–20] | 0.33 |
| Extra-intestinal manifestation | 92 [46%] | 69 [51.5%] | 23 [34.8%] | 0.03 |
| Corticosteroids | 43 [21.5%] | 24 [17.9%] | 19 [28.8%] | 0.08 |
| Anti-TNFα or immunomodulators | 164 [82%] | 113 [84.3%] | 51 [77.3%] | 0.22 |
| Surgery for IBD | 52 [26%] | 49 [36.6%] | 3 [4.5%] | <0.001 |
| Physical activity | 101 [50.5%] | 60 [44.8%] | 41 [62.1%] | 0.02 |
| Pain [any type] | 151 [75.5%] | 112 [83.6%] | 39 [59.1%] | <0.001 |
| Abdominal pain | 124 [62%] | 92 [68.7%] | 32 [48.5%] | 0.006 |
| Central sensitization | 35 [17.5%] | 28 [20.9] | 7 [10.6] | 0.07 |
| Active disease | 103 [56.5%] | 85 [63.4%] | 17 [24.2%] | p < 0.001 |
Data are mean [range] for age, number [%], mean ± SD, or median [IQR]. IBD = inflammatory bowel disease; BMI = body mass index; TNF = tumour necrosis factor. Central sensitization was defined as pain with cutaneous hyperalgesia, sensorial experience of pain and pain descriptors of neuropathic pain, and a DN4 score [Douleur Neuropathique 4 questions]21 >4. Active disease was defined as Harvey–Bradshaw Index16 >4 for CD patients and partial Mayo score19 >2 for UC patients.
3.2. Prevalence of pain
Three-quarters of IBD patients complained of pain of any type. Sixty two per cent of the overall population reported abdominal pain [i.e. 82.1% of patients complaining of pain], and 17.5% of the overall population had abdominal pain with a central sensitization [i.e. 28.2% of patients complaining of abdominal pain]. Prevalence of pain [p < 0.001] and abdominal pain [p = 0.006] was 40% higher in CD patients than in UC patients [Table 1]. Eighty-nine per cent of patients had complained of pain for more than 6 months and 62% for more than 5 years. Pain was reported as acute pain attacks on a constant painful background in 28% of the patients and as acute pain attack with pain-free intervals in 48% of the patients. The characteristics of patients with pain were compared with those of patients without pain [Table 2]. Patients with pain were younger [p = 0.04], more often female [adjusted p = 0.005], had a lower body mass index [BMI] [adjusted p = 0.005], suffered from CD more often than UC [adjusted p < 0.003] and had previously undergone surgery related to IBD [adjusted p = 0.05]. Multivariate analysis confirmed that age (aOR = 0.97 [95% CI = 0.94–0.99], p = 0.02), sex [female] (aOR = 2.89 [95% CI = 1.41–6.09], p = 0.004) and CD (aOR = 2.99 [95% CI = 1.4–6.52], p = 0.005) were independent risk factors for pain.
Characteristics of patients with and without pain
| Pain | No pain | p | Adjusted p | |
|---|---|---|---|---|
| N | 151 [75.5%] | 49 [24.5%] | ||
| Age | 42.9 [19–78] | 49.7 [19–87] | 0.019 | 0.04 |
| Sex male [%] | 61 [40.4%] | 32 [65.3%] | 0.002 | 0.005 |
| Weight [kg] | 70.3 ± 15.3 | 77 ± 14 | 0.002 | 0.005 |
| Height [cm] | 170 ± 9 | 173 ± 9 | 0.046 | 0.085 |
| BMI [kg/m2] | 23.4 [20.9–26.5] | 26.1 [23.4–28.1] | 0.002 | 0.005 |
| Smoking | 40 [26.5] | 8 [16.3] | 0.15 | 0.225 |
| Alcohol > 10 U/week | 16 [10.6] | 10 [20.4] | 0.076 | 0.127 |
| Crohn’s/ulcerative colitis: | 112 [74.2%]/39 [25.8%] | 22 [44.9]/27 [55.1%] | <0.001 | 0.003 |
| Duration of IBD | 13 [7–21] | 16 [8–24] | 0.24 | 0.31 |
| Corticosteroids | 33 [21.9%] | 10 [20.4%] | 0.83 | 0.89 |
| Anti-TNFα or immunomodulators | 126 [83.4%] | 38 [77.6%] | 0.35 | 0.43 |
| Abdominal pain | 124 [82.1%] | 0 | NA | |
| Extra-intestinal pain | 85 [56.2%] | 0 | NA | |
| Surgery for IBD | 45 [29.8%] | 7 [14.3%] | 0.03 | 0.05 |
| Pain | No pain | p | Adjusted p | |
|---|---|---|---|---|
| N | 151 [75.5%] | 49 [24.5%] | ||
| Age | 42.9 [19–78] | 49.7 [19–87] | 0.019 | 0.04 |
| Sex male [%] | 61 [40.4%] | 32 [65.3%] | 0.002 | 0.005 |
| Weight [kg] | 70.3 ± 15.3 | 77 ± 14 | 0.002 | 0.005 |
| Height [cm] | 170 ± 9 | 173 ± 9 | 0.046 | 0.085 |
| BMI [kg/m2] | 23.4 [20.9–26.5] | 26.1 [23.4–28.1] | 0.002 | 0.005 |
| Smoking | 40 [26.5] | 8 [16.3] | 0.15 | 0.225 |
| Alcohol > 10 U/week | 16 [10.6] | 10 [20.4] | 0.076 | 0.127 |
| Crohn’s/ulcerative colitis: | 112 [74.2%]/39 [25.8%] | 22 [44.9]/27 [55.1%] | <0.001 | 0.003 |
| Duration of IBD | 13 [7–21] | 16 [8–24] | 0.24 | 0.31 |
| Corticosteroids | 33 [21.9%] | 10 [20.4%] | 0.83 | 0.89 |
| Anti-TNFα or immunomodulators | 126 [83.4%] | 38 [77.6%] | 0.35 | 0.43 |
| Abdominal pain | 124 [82.1%] | 0 | NA | |
| Extra-intestinal pain | 85 [56.2%] | 0 | NA | |
| Surgery for IBD | 45 [29.8%] | 7 [14.3%] | 0.03 | 0.05 |
Data are mean [range] for age, number [%], mean ± SD or median [IQR]. IBD = inflammatory bowel disease; BMI = body mass index; TNF = tumour necrosis factor. Active disease was defined as Harvey–Bradshaw Index16 >4 for CD patients and partial Mayo score19 >2 for UC patients. Adj. p: adjusted p values using the method of Benjamini and Hochberg.
Characteristics of patients with and without pain
| Pain | No pain | p | Adjusted p | |
|---|---|---|---|---|
| N | 151 [75.5%] | 49 [24.5%] | ||
| Age | 42.9 [19–78] | 49.7 [19–87] | 0.019 | 0.04 |
| Sex male [%] | 61 [40.4%] | 32 [65.3%] | 0.002 | 0.005 |
| Weight [kg] | 70.3 ± 15.3 | 77 ± 14 | 0.002 | 0.005 |
| Height [cm] | 170 ± 9 | 173 ± 9 | 0.046 | 0.085 |
| BMI [kg/m2] | 23.4 [20.9–26.5] | 26.1 [23.4–28.1] | 0.002 | 0.005 |
| Smoking | 40 [26.5] | 8 [16.3] | 0.15 | 0.225 |
| Alcohol > 10 U/week | 16 [10.6] | 10 [20.4] | 0.076 | 0.127 |
| Crohn’s/ulcerative colitis: | 112 [74.2%]/39 [25.8%] | 22 [44.9]/27 [55.1%] | <0.001 | 0.003 |
| Duration of IBD | 13 [7–21] | 16 [8–24] | 0.24 | 0.31 |
| Corticosteroids | 33 [21.9%] | 10 [20.4%] | 0.83 | 0.89 |
| Anti-TNFα or immunomodulators | 126 [83.4%] | 38 [77.6%] | 0.35 | 0.43 |
| Abdominal pain | 124 [82.1%] | 0 | NA | |
| Extra-intestinal pain | 85 [56.2%] | 0 | NA | |
| Surgery for IBD | 45 [29.8%] | 7 [14.3%] | 0.03 | 0.05 |
| Pain | No pain | p | Adjusted p | |
|---|---|---|---|---|
| N | 151 [75.5%] | 49 [24.5%] | ||
| Age | 42.9 [19–78] | 49.7 [19–87] | 0.019 | 0.04 |
| Sex male [%] | 61 [40.4%] | 32 [65.3%] | 0.002 | 0.005 |
| Weight [kg] | 70.3 ± 15.3 | 77 ± 14 | 0.002 | 0.005 |
| Height [cm] | 170 ± 9 | 173 ± 9 | 0.046 | 0.085 |
| BMI [kg/m2] | 23.4 [20.9–26.5] | 26.1 [23.4–28.1] | 0.002 | 0.005 |
| Smoking | 40 [26.5] | 8 [16.3] | 0.15 | 0.225 |
| Alcohol > 10 U/week | 16 [10.6] | 10 [20.4] | 0.076 | 0.127 |
| Crohn’s/ulcerative colitis: | 112 [74.2%]/39 [25.8%] | 22 [44.9]/27 [55.1%] | <0.001 | 0.003 |
| Duration of IBD | 13 [7–21] | 16 [8–24] | 0.24 | 0.31 |
| Corticosteroids | 33 [21.9%] | 10 [20.4%] | 0.83 | 0.89 |
| Anti-TNFα or immunomodulators | 126 [83.4%] | 38 [77.6%] | 0.35 | 0.43 |
| Abdominal pain | 124 [82.1%] | 0 | NA | |
| Extra-intestinal pain | 85 [56.2%] | 0 | NA | |
| Surgery for IBD | 45 [29.8%] | 7 [14.3%] | 0.03 | 0.05 |
Data are mean [range] for age, number [%], mean ± SD or median [IQR]. IBD = inflammatory bowel disease; BMI = body mass index; TNF = tumour necrosis factor. Active disease was defined as Harvey–Bradshaw Index16 >4 for CD patients and partial Mayo score19 >2 for UC patients. Adj. p: adjusted p values using the method of Benjamini and Hochberg.
The abdomen was the most frequent pain location [80%], but more than 50% of IBD patients with pain complained of extra-intestinal pain. Pain was reported throughout the body [Figure 1], but back pain was the most frequent extra-intestinal pain [40%]. Oral analgesics were used to treat pain by 80.8% of IBD patients with pain: paracetamol in 68%, antispasmodic drugs in 39.7%, opioids [weak and strong] in 29% and non-steroidal anti-inflammatory drugs [NSAIDs] in 20%. Seventeen per cent of the patients were under antidepressants, but to treat depression not pain. Thirty per cent were treated with different types of physical medicine therapies [physiotherapy, massage, osteopathy, acupuncture], 13.2% used some psychotherapy and 7.3% had nerve blocks.
![Pain localization in patients complaining of pain [N = 151].](https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/ecco-jcc/16/9/10.1093_ecco-jcc_jjac051/1/m_jjac051f0001.jpeg?Expires=1749113697&Signature=xpc9~OlGR8BR0iAD4rbmHZ6sQKE5C4BeQYfJspusjp-rHOrSG16lbTHcpdmN~s4PUkYdMNNNeyZOJ1~D2DE6vQpTtrGaNbeJpoxfnPJKkR2st4dH~bj~pDD0S73w5CRqvkIpOCY8Bs8ERw4UBSFBUJigvL~cemBbtVgEm4JuKM-rEnqiVoB9Bi4~oxJPXiFen4cVc4TW9kUd9~0y0-pCCEEdWY0ctFgx-nD6cjdngAuBVDkqVPzanxY6aqmONoS4ULFYmie8qult52b5PRRTC5JapBjG-U6gDVJ0k6hBRwuRQSRzLODqbL0Huj2CjdRwv-TewPFlDuz3VHyp8-vssg__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Pain localization in patients complaining of pain [N = 151].
3.3. Central sensitization: prevalence and epidemiology
Among the 124 patients with abdominal pain, 35 [28.5%] described pain with clinical presentation of central sensitization. Table 3 presents the characteristics of patients complaining of abdominal pain with and without central sensitization characteristics. Patients with central sensitization symptoms were older [adjusted p = 0.04] and had more extra-intestinal manifestations [adjusted p = 0.03]. The prevalence was similar in CD and UC [adjusted p = 0.43]. IBD patients with central sensitization more often had active disease [adjusted p = 0.003]. CD patients with clinical presentation of central sensitization had more severe disease [higher HBI and PRO2 scores for CD patients] [adjusted p < 0.003]. However, the prevalence was independent of the severity of the disease in UC patients. The duration of the disease and proportion of cigarette smokers were similar in both groups. We note that history of previous abdominal surgery for IBD or other indications was not associated with central sensitization. Multivariate analysis confirmed that severity of CD [HBI] (aOR = 1.29 [95% CI = 1.1–1.5], p = 0.001) was an independent risk factor for central sensitization, but not age (aOR = 1.02 [95% CI = 0.99–1.07], p = 0.17), nor extra-intestinal manifestation (aOR = 1.6 [95% CI = 0.5–4.8, p = 0.42].
Characteristics of patients complaining of abdominal pain with and without clinical presentation of central sensitization
| Abdominal pain | With central sensitization | Without central sensitization | p | Adjusted p | |
|---|---|---|---|---|---|
| N | 124 | 35 [28.2%] | 89 [71.8%] | ||
| Age | 41.6 [19–78] | 45.6 [20–74] | 40.0 [19–78] | 0.018 | 0.04 |
| Sex male [%] | 56 [45.2%] | 18 [51.4%] | 38 [42.7%] | 0.38 | 0.45 |
| Weight [kg] | 70.4 ± 15.6 | 74.5 ± 17.2 | 68.8 ± 14.7 | 0.11 | 0.18 |
| Height [cm] | 171 ± 9 | 173 ± 8 | 170 ± 9 | 0.13 | 0.20 |
| BMI [kg/m2] | 23 [20.8–26.2] | 23.6 [21.7–27.0] | 22.6 [20.6–25.7] | 0.19 | 0.26 |
| Smoking | 30 [24.2] | 10 [28.6] | 20 [22.5] | 0.47 | 0.55 |
| Alcohol > 10 U/week | 13 [10.5] | 3 [8.6] | 10 [11.2] | 1 | 1 |
| Crohn’s/ulcerative colitis | 92 [74.2%]/32 [25.8%] | 28 [80%]/7 [20%] | 64 [71.9%]/25 [28.1%] | 0.35 | 0.43 |
| Duration of IBD | 11 [6–19] | 14 [6.5–22.5] | 11 [6–19] | 0.36 | 0.44 |
| Extra-intestinal manifestation | 67 [54%] | 25 [71.4%] | 42 [47.2%] | 0.015 | 0.03 |
| Corticosteroids | 28 [22.6%] | 5 [14.3%] | 23 [25.8%] | 0.17 | 0.25 |
| Anti-TNFα or immunomodulators | 102 [82.3%] | 30 [85.7%] | 72 [80.9%] | 0.53 | 0.60 |
| Active disease | 79 [63.7%] | 30 [85.7%] | 49 [55.1%] | 0.001 | 0.003 |
| Surgery for IBD | 37 [29.8%] | 10 [28.6%] | 27 [30.3%] | 0.85 | 0.90 |
| Abdominal surgery [all indications] | 53 [42.7%] | 12 [34.3%] | 41 [46.1%] | 0.23 | 0.30 |
| Laparotomy | 33 [26.6%] | 10 [28.6%] | 23 [25.8%] | 0.76 | 0.83 |
| Concordance between pain and scar [n = 53] | 31 [58.5%] | 10 [76.9%] | 21 [52.5%] | 0.12 | 0.19 |
| Hyperalgesia to pinprick | 9 [7.3%] | 5 [14.3%] | 4 [4.5%] | 0.058 | 0.10 |
| Functional colopathy | 22 [17.7] | 7 [20] | 15 [16.9] | 0.68 | 0.76 |
| Harvey–Bradshaw score [CD: n = 92] | 6 [4–8] | 8 [6–11] | 5 [3–7] | <0.001 | 0.003 |
| PRO2 score [CD: n = 92] | 11 [7–16] | 16 [11–22] | 9.5 [5–12.25] | <0.001 | 0.003 |
| MAYO score [UC: n = 32] | 3 [1.75–5.25] | 5 [3.25–6.75] | 3 [1.25–4] | 0.19 | 0.26 |
| PRO2 score [UC: n = 32] | 2 [1–4] | 4 [1.75–4.75] | 1.5 [1–3] | 0.22 | 0.30 |
| Abdominal pain | With central sensitization | Without central sensitization | p | Adjusted p | |
|---|---|---|---|---|---|
| N | 124 | 35 [28.2%] | 89 [71.8%] | ||
| Age | 41.6 [19–78] | 45.6 [20–74] | 40.0 [19–78] | 0.018 | 0.04 |
| Sex male [%] | 56 [45.2%] | 18 [51.4%] | 38 [42.7%] | 0.38 | 0.45 |
| Weight [kg] | 70.4 ± 15.6 | 74.5 ± 17.2 | 68.8 ± 14.7 | 0.11 | 0.18 |
| Height [cm] | 171 ± 9 | 173 ± 8 | 170 ± 9 | 0.13 | 0.20 |
| BMI [kg/m2] | 23 [20.8–26.2] | 23.6 [21.7–27.0] | 22.6 [20.6–25.7] | 0.19 | 0.26 |
| Smoking | 30 [24.2] | 10 [28.6] | 20 [22.5] | 0.47 | 0.55 |
| Alcohol > 10 U/week | 13 [10.5] | 3 [8.6] | 10 [11.2] | 1 | 1 |
| Crohn’s/ulcerative colitis | 92 [74.2%]/32 [25.8%] | 28 [80%]/7 [20%] | 64 [71.9%]/25 [28.1%] | 0.35 | 0.43 |
| Duration of IBD | 11 [6–19] | 14 [6.5–22.5] | 11 [6–19] | 0.36 | 0.44 |
| Extra-intestinal manifestation | 67 [54%] | 25 [71.4%] | 42 [47.2%] | 0.015 | 0.03 |
| Corticosteroids | 28 [22.6%] | 5 [14.3%] | 23 [25.8%] | 0.17 | 0.25 |
| Anti-TNFα or immunomodulators | 102 [82.3%] | 30 [85.7%] | 72 [80.9%] | 0.53 | 0.60 |
| Active disease | 79 [63.7%] | 30 [85.7%] | 49 [55.1%] | 0.001 | 0.003 |
| Surgery for IBD | 37 [29.8%] | 10 [28.6%] | 27 [30.3%] | 0.85 | 0.90 |
| Abdominal surgery [all indications] | 53 [42.7%] | 12 [34.3%] | 41 [46.1%] | 0.23 | 0.30 |
| Laparotomy | 33 [26.6%] | 10 [28.6%] | 23 [25.8%] | 0.76 | 0.83 |
| Concordance between pain and scar [n = 53] | 31 [58.5%] | 10 [76.9%] | 21 [52.5%] | 0.12 | 0.19 |
| Hyperalgesia to pinprick | 9 [7.3%] | 5 [14.3%] | 4 [4.5%] | 0.058 | 0.10 |
| Functional colopathy | 22 [17.7] | 7 [20] | 15 [16.9] | 0.68 | 0.76 |
| Harvey–Bradshaw score [CD: n = 92] | 6 [4–8] | 8 [6–11] | 5 [3–7] | <0.001 | 0.003 |
| PRO2 score [CD: n = 92] | 11 [7–16] | 16 [11–22] | 9.5 [5–12.25] | <0.001 | 0.003 |
| MAYO score [UC: n = 32] | 3 [1.75–5.25] | 5 [3.25–6.75] | 3 [1.25–4] | 0.19 | 0.26 |
| PRO2 score [UC: n = 32] | 2 [1–4] | 4 [1.75–4.75] | 1.5 [1–3] | 0.22 | 0.30 |
Data are mean [range] for age, number [%], mean ± SD or median [IQR]. Central sensitization is defined as pain with cutaneous hyperalgesia, sensorial experience of pain and pain descriptors of neuropathic pain, and a DN4 score [Douleur Neuropathique 4 questions]21 >4. IBD = inflammatory bowel disease; BMI = body mass index; TNF = tumour necrosis factor; CD = Crohn’s disease; UC = ulcerative colitis. Active disease was defined as HBI16 >4 for CD patients and partial Mayo score19 >2 for UC patients. Adjusted p: adjusted p values using the method of Benjamini and Hochberg.
Characteristics of patients complaining of abdominal pain with and without clinical presentation of central sensitization
| Abdominal pain | With central sensitization | Without central sensitization | p | Adjusted p | |
|---|---|---|---|---|---|
| N | 124 | 35 [28.2%] | 89 [71.8%] | ||
| Age | 41.6 [19–78] | 45.6 [20–74] | 40.0 [19–78] | 0.018 | 0.04 |
| Sex male [%] | 56 [45.2%] | 18 [51.4%] | 38 [42.7%] | 0.38 | 0.45 |
| Weight [kg] | 70.4 ± 15.6 | 74.5 ± 17.2 | 68.8 ± 14.7 | 0.11 | 0.18 |
| Height [cm] | 171 ± 9 | 173 ± 8 | 170 ± 9 | 0.13 | 0.20 |
| BMI [kg/m2] | 23 [20.8–26.2] | 23.6 [21.7–27.0] | 22.6 [20.6–25.7] | 0.19 | 0.26 |
| Smoking | 30 [24.2] | 10 [28.6] | 20 [22.5] | 0.47 | 0.55 |
| Alcohol > 10 U/week | 13 [10.5] | 3 [8.6] | 10 [11.2] | 1 | 1 |
| Crohn’s/ulcerative colitis | 92 [74.2%]/32 [25.8%] | 28 [80%]/7 [20%] | 64 [71.9%]/25 [28.1%] | 0.35 | 0.43 |
| Duration of IBD | 11 [6–19] | 14 [6.5–22.5] | 11 [6–19] | 0.36 | 0.44 |
| Extra-intestinal manifestation | 67 [54%] | 25 [71.4%] | 42 [47.2%] | 0.015 | 0.03 |
| Corticosteroids | 28 [22.6%] | 5 [14.3%] | 23 [25.8%] | 0.17 | 0.25 |
| Anti-TNFα or immunomodulators | 102 [82.3%] | 30 [85.7%] | 72 [80.9%] | 0.53 | 0.60 |
| Active disease | 79 [63.7%] | 30 [85.7%] | 49 [55.1%] | 0.001 | 0.003 |
| Surgery for IBD | 37 [29.8%] | 10 [28.6%] | 27 [30.3%] | 0.85 | 0.90 |
| Abdominal surgery [all indications] | 53 [42.7%] | 12 [34.3%] | 41 [46.1%] | 0.23 | 0.30 |
| Laparotomy | 33 [26.6%] | 10 [28.6%] | 23 [25.8%] | 0.76 | 0.83 |
| Concordance between pain and scar [n = 53] | 31 [58.5%] | 10 [76.9%] | 21 [52.5%] | 0.12 | 0.19 |
| Hyperalgesia to pinprick | 9 [7.3%] | 5 [14.3%] | 4 [4.5%] | 0.058 | 0.10 |
| Functional colopathy | 22 [17.7] | 7 [20] | 15 [16.9] | 0.68 | 0.76 |
| Harvey–Bradshaw score [CD: n = 92] | 6 [4–8] | 8 [6–11] | 5 [3–7] | <0.001 | 0.003 |
| PRO2 score [CD: n = 92] | 11 [7–16] | 16 [11–22] | 9.5 [5–12.25] | <0.001 | 0.003 |
| MAYO score [UC: n = 32] | 3 [1.75–5.25] | 5 [3.25–6.75] | 3 [1.25–4] | 0.19 | 0.26 |
| PRO2 score [UC: n = 32] | 2 [1–4] | 4 [1.75–4.75] | 1.5 [1–3] | 0.22 | 0.30 |
| Abdominal pain | With central sensitization | Without central sensitization | p | Adjusted p | |
|---|---|---|---|---|---|
| N | 124 | 35 [28.2%] | 89 [71.8%] | ||
| Age | 41.6 [19–78] | 45.6 [20–74] | 40.0 [19–78] | 0.018 | 0.04 |
| Sex male [%] | 56 [45.2%] | 18 [51.4%] | 38 [42.7%] | 0.38 | 0.45 |
| Weight [kg] | 70.4 ± 15.6 | 74.5 ± 17.2 | 68.8 ± 14.7 | 0.11 | 0.18 |
| Height [cm] | 171 ± 9 | 173 ± 8 | 170 ± 9 | 0.13 | 0.20 |
| BMI [kg/m2] | 23 [20.8–26.2] | 23.6 [21.7–27.0] | 22.6 [20.6–25.7] | 0.19 | 0.26 |
| Smoking | 30 [24.2] | 10 [28.6] | 20 [22.5] | 0.47 | 0.55 |
| Alcohol > 10 U/week | 13 [10.5] | 3 [8.6] | 10 [11.2] | 1 | 1 |
| Crohn’s/ulcerative colitis | 92 [74.2%]/32 [25.8%] | 28 [80%]/7 [20%] | 64 [71.9%]/25 [28.1%] | 0.35 | 0.43 |
| Duration of IBD | 11 [6–19] | 14 [6.5–22.5] | 11 [6–19] | 0.36 | 0.44 |
| Extra-intestinal manifestation | 67 [54%] | 25 [71.4%] | 42 [47.2%] | 0.015 | 0.03 |
| Corticosteroids | 28 [22.6%] | 5 [14.3%] | 23 [25.8%] | 0.17 | 0.25 |
| Anti-TNFα or immunomodulators | 102 [82.3%] | 30 [85.7%] | 72 [80.9%] | 0.53 | 0.60 |
| Active disease | 79 [63.7%] | 30 [85.7%] | 49 [55.1%] | 0.001 | 0.003 |
| Surgery for IBD | 37 [29.8%] | 10 [28.6%] | 27 [30.3%] | 0.85 | 0.90 |
| Abdominal surgery [all indications] | 53 [42.7%] | 12 [34.3%] | 41 [46.1%] | 0.23 | 0.30 |
| Laparotomy | 33 [26.6%] | 10 [28.6%] | 23 [25.8%] | 0.76 | 0.83 |
| Concordance between pain and scar [n = 53] | 31 [58.5%] | 10 [76.9%] | 21 [52.5%] | 0.12 | 0.19 |
| Hyperalgesia to pinprick | 9 [7.3%] | 5 [14.3%] | 4 [4.5%] | 0.058 | 0.10 |
| Functional colopathy | 22 [17.7] | 7 [20] | 15 [16.9] | 0.68 | 0.76 |
| Harvey–Bradshaw score [CD: n = 92] | 6 [4–8] | 8 [6–11] | 5 [3–7] | <0.001 | 0.003 |
| PRO2 score [CD: n = 92] | 11 [7–16] | 16 [11–22] | 9.5 [5–12.25] | <0.001 | 0.003 |
| MAYO score [UC: n = 32] | 3 [1.75–5.25] | 5 [3.25–6.75] | 3 [1.25–4] | 0.19 | 0.26 |
| PRO2 score [UC: n = 32] | 2 [1–4] | 4 [1.75–4.75] | 1.5 [1–3] | 0.22 | 0.30 |
Data are mean [range] for age, number [%], mean ± SD or median [IQR]. Central sensitization is defined as pain with cutaneous hyperalgesia, sensorial experience of pain and pain descriptors of neuropathic pain, and a DN4 score [Douleur Neuropathique 4 questions]21 >4. IBD = inflammatory bowel disease; BMI = body mass index; TNF = tumour necrosis factor; CD = Crohn’s disease; UC = ulcerative colitis. Active disease was defined as HBI16 >4 for CD patients and partial Mayo score19 >2 for UC patients. Adjusted p: adjusted p values using the method of Benjamini and Hochberg.
When clinical presentation of central sensitisation occurred, the intensity of current pain and of pain averaged over the last month, together with the maximal pain severity during the last month, were significantly greater [adjusted p < 0.003] compared with pain without central sensitization [Figure 2]. Breakthrough pain lasting hours or more was more often reported when there was central sensitization: 68% vs 37% of patients with and without central sensitization respectively [adjusted p = 0.02]. Sensory and emotional pain descriptors from the short French version of the McGill questionnaire were different with central sensitization [Table 4]. The most often used pain sensory descriptors were electric shock, crushing, burning, tingling and heavy.
Pain descriptors from the short French version of the McGill questionnaire used by patients complaining of abdominal pain with and without central sensitization characteristics
| Abdominal pain | With central sensitization | Without central sensitization | p | Adjusted p | |
|---|---|---|---|---|---|
| Shouting | 1 [0–2] | 2 [0–3] | 1 [0–2] | 0.21 | 0.29 |
| Piercing | 1 [0–2] | 2 [0–2.5] | 1 [0–2] | 0.10 | 0.18 |
| Electric shock | 0 [0–0] | 0 [0–2] | 0 [0–0] | <0.001 | 0.003 |
| Stabbing | 1 [0–2] | 2 [0.5–3] | 1 [0–2] | 0.14 | 0.21 |
| Crushing | 0 [0–2] | 1 [0–2.5] | 0 [0–1] | 0.012 | 0.025 |
| Nagging | 0 [0–2] | 1 [0–2] | 0 [0–1] | 0.057 | 0.09 |
| Burning | 0 [0–2] | 1 [0–2] | 0 [0–1] | 0.003 | 0.009 |
| Tingling | 0 [0–0] | 0 [0–1.5] | 0 [0–0] | <0.001 | 0.003 |
| Heavy | 2 [0–2] | 2 [2–3] | 1 [0–2] | 0.001 | 0.003 |
| Exhausting | 2 [0–3] | 3 [2–4] | 2 [0–3] | <0.001 | 0.003 |
| Frightful | 0 [0–2] | 2 [0–3] | 0 [0–2] | 0.002 | 0.006 |
| Haunting | 0 [0–2] | 1 [0–2] | 0 [0–1] | <0.001 | 0.003 |
| Unbearable | 1 [0–2] | 2 [1–2.5] | 1 [0–2] | 0.001 | 0.003 |
| Annoying | 2 [0–3] | 2 [2–3] | 1 [0–3] | 0.007 | 0.012 |
| Frustrating | 1 [0–2] | 2 [0–3] | 0 [0–2] | 0.07 | 0.12 |
| Depressing | 1 [0–2] | 2 [0–3] | 1 [0–2] | 0.03 | 0.059 |
| Abdominal pain | With central sensitization | Without central sensitization | p | Adjusted p | |
|---|---|---|---|---|---|
| Shouting | 1 [0–2] | 2 [0–3] | 1 [0–2] | 0.21 | 0.29 |
| Piercing | 1 [0–2] | 2 [0–2.5] | 1 [0–2] | 0.10 | 0.18 |
| Electric shock | 0 [0–0] | 0 [0–2] | 0 [0–0] | <0.001 | 0.003 |
| Stabbing | 1 [0–2] | 2 [0.5–3] | 1 [0–2] | 0.14 | 0.21 |
| Crushing | 0 [0–2] | 1 [0–2.5] | 0 [0–1] | 0.012 | 0.025 |
| Nagging | 0 [0–2] | 1 [0–2] | 0 [0–1] | 0.057 | 0.09 |
| Burning | 0 [0–2] | 1 [0–2] | 0 [0–1] | 0.003 | 0.009 |
| Tingling | 0 [0–0] | 0 [0–1.5] | 0 [0–0] | <0.001 | 0.003 |
| Heavy | 2 [0–2] | 2 [2–3] | 1 [0–2] | 0.001 | 0.003 |
| Exhausting | 2 [0–3] | 3 [2–4] | 2 [0–3] | <0.001 | 0.003 |
| Frightful | 0 [0–2] | 2 [0–3] | 0 [0–2] | 0.002 | 0.006 |
| Haunting | 0 [0–2] | 1 [0–2] | 0 [0–1] | <0.001 | 0.003 |
| Unbearable | 1 [0–2] | 2 [1–2.5] | 1 [0–2] | 0.001 | 0.003 |
| Annoying | 2 [0–3] | 2 [2–3] | 1 [0–3] | 0.007 | 0.012 |
| Frustrating | 1 [0–2] | 2 [0–3] | 0 [0–2] | 0.07 | 0.12 |
| Depressing | 1 [0–2] | 2 [0–3] | 1 [0–2] | 0.03 | 0.059 |
Descriptor scale: 0 = no pain, 1 = mild, 2 = moderate, 3 = strong, 4 = very severe. Adjusted p: adjusted p values using the method of Benjamini and Hochberg.
Pain descriptors from the short French version of the McGill questionnaire used by patients complaining of abdominal pain with and without central sensitization characteristics
| Abdominal pain | With central sensitization | Without central sensitization | p | Adjusted p | |
|---|---|---|---|---|---|
| Shouting | 1 [0–2] | 2 [0–3] | 1 [0–2] | 0.21 | 0.29 |
| Piercing | 1 [0–2] | 2 [0–2.5] | 1 [0–2] | 0.10 | 0.18 |
| Electric shock | 0 [0–0] | 0 [0–2] | 0 [0–0] | <0.001 | 0.003 |
| Stabbing | 1 [0–2] | 2 [0.5–3] | 1 [0–2] | 0.14 | 0.21 |
| Crushing | 0 [0–2] | 1 [0–2.5] | 0 [0–1] | 0.012 | 0.025 |
| Nagging | 0 [0–2] | 1 [0–2] | 0 [0–1] | 0.057 | 0.09 |
| Burning | 0 [0–2] | 1 [0–2] | 0 [0–1] | 0.003 | 0.009 |
| Tingling | 0 [0–0] | 0 [0–1.5] | 0 [0–0] | <0.001 | 0.003 |
| Heavy | 2 [0–2] | 2 [2–3] | 1 [0–2] | 0.001 | 0.003 |
| Exhausting | 2 [0–3] | 3 [2–4] | 2 [0–3] | <0.001 | 0.003 |
| Frightful | 0 [0–2] | 2 [0–3] | 0 [0–2] | 0.002 | 0.006 |
| Haunting | 0 [0–2] | 1 [0–2] | 0 [0–1] | <0.001 | 0.003 |
| Unbearable | 1 [0–2] | 2 [1–2.5] | 1 [0–2] | 0.001 | 0.003 |
| Annoying | 2 [0–3] | 2 [2–3] | 1 [0–3] | 0.007 | 0.012 |
| Frustrating | 1 [0–2] | 2 [0–3] | 0 [0–2] | 0.07 | 0.12 |
| Depressing | 1 [0–2] | 2 [0–3] | 1 [0–2] | 0.03 | 0.059 |
| Abdominal pain | With central sensitization | Without central sensitization | p | Adjusted p | |
|---|---|---|---|---|---|
| Shouting | 1 [0–2] | 2 [0–3] | 1 [0–2] | 0.21 | 0.29 |
| Piercing | 1 [0–2] | 2 [0–2.5] | 1 [0–2] | 0.10 | 0.18 |
| Electric shock | 0 [0–0] | 0 [0–2] | 0 [0–0] | <0.001 | 0.003 |
| Stabbing | 1 [0–2] | 2 [0.5–3] | 1 [0–2] | 0.14 | 0.21 |
| Crushing | 0 [0–2] | 1 [0–2.5] | 0 [0–1] | 0.012 | 0.025 |
| Nagging | 0 [0–2] | 1 [0–2] | 0 [0–1] | 0.057 | 0.09 |
| Burning | 0 [0–2] | 1 [0–2] | 0 [0–1] | 0.003 | 0.009 |
| Tingling | 0 [0–0] | 0 [0–1.5] | 0 [0–0] | <0.001 | 0.003 |
| Heavy | 2 [0–2] | 2 [2–3] | 1 [0–2] | 0.001 | 0.003 |
| Exhausting | 2 [0–3] | 3 [2–4] | 2 [0–3] | <0.001 | 0.003 |
| Frightful | 0 [0–2] | 2 [0–3] | 0 [0–2] | 0.002 | 0.006 |
| Haunting | 0 [0–2] | 1 [0–2] | 0 [0–1] | <0.001 | 0.003 |
| Unbearable | 1 [0–2] | 2 [1–2.5] | 1 [0–2] | 0.001 | 0.003 |
| Annoying | 2 [0–3] | 2 [2–3] | 1 [0–3] | 0.007 | 0.012 |
| Frustrating | 1 [0–2] | 2 [0–3] | 0 [0–2] | 0.07 | 0.12 |
| Depressing | 1 [0–2] | 2 [0–3] | 1 [0–2] | 0.03 | 0.059 |
Descriptor scale: 0 = no pain, 1 = mild, 2 = moderate, 3 = strong, 4 = very severe. Adjusted p: adjusted p values using the method of Benjamini and Hochberg.
![Current pain, pain averaged during the last 4 weeks and maximal pain intensity during the last month in patients with and without clinical presentation of central sensitization. Data are median, boxes = 25–75 percentiles, whiskers = 10–90 percentiles. Pain scores were measured using a 0–10 cm visual analogue scale [VAS]. ***p < 0.001.](https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/ecco-jcc/16/9/10.1093_ecco-jcc_jjac051/1/m_jjac051f0002.jpeg?Expires=1749113697&Signature=WaXJjXRGSdSngCx12TliBEMs4hi4zZmU9qrViIA6qO12zJsz~caBwNklHPuEUatCbpslZeUuDvrNDq7BvWY9laoG2cnh02T~j54orqc5UYadgvvD7Dl7L5~B-2JfctN6JFKH48HycLHoj9dAKAknYfpEFAO0A4kWYBP2wXjfN4ve5~Z~TfRYkBBQ4gRBKQHPZ9NPGPgaSbhECvE1R6zEGKlwlQgm~nNpQARNYGuHvdSUlKpXJ~uRdkyklhsfDCIARMs3uBjzanwfhVMpXc2S-qyOj-Dp0dCvkOP8pG87spFeprqovbTP8BNMIrYvrsudjVaHCMOOooEunSRFolZ3uA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Current pain, pain averaged during the last 4 weeks and maximal pain intensity during the last month in patients with and without clinical presentation of central sensitization. Data are median, boxes = 25–75 percentiles, whiskers = 10–90 percentiles. Pain scores were measured using a 0–10 cm visual analogue scale [VAS]. ***p < 0.001.
3.4. Impact of pain on anxiety, depression and quality of life
The impacts of pain on anxiety, depression and quality of life are summarized in Table 5. Pain increased two to four times [adjusted p < 0.003] the anxiety score, depression score, impact on global HRQoL score and score of each item of the HRQoL. Pain associated with central sensitization significantly impaired overall quality of life [adjusted p < 0.003] together with each item of the HRQoL score compared with abdominal pain without central sensitization [Table 6].
Impact of pain on anxiety, depression and quality of life [QoL]
| Global population | Patients with pain | Patients without pain | p | Adjusted p | |
|---|---|---|---|---|---|
| N | 200 | 151 [75.5] | 49 [24.5] | ||
| Anxiety score [0–21] | 7 [4–10] | 9 [6–11] | 4 [2–6] | <0.001 | 0.003 |
| Depression score [0–21] | 4 [2–8] | 5.5 [3–9] | 2 [1–3] | <0.001 | 0.003 |
| QoL: general activitya | 3 [1–6] | 4 [2–7] | 0 [0–3] | <0.001 | 0.003 |
| QoL: mooda | 3 [1–6] | 4 [1.5–6] | 0 [0–2] | <0.001 | 0.003 |
| QoL: ability to ambulatea | 1 [0–5] | 2 [0–6] | 0 [0–0] | <0.001 | 0.003 |
| QoL: usual worka | 3 [0–6] | 4 [1–7] | 0 [0–2] | <0.001 | 0.003 |
| QoL: relationship with othersa | 1.5 [0–5] | 2 [0–6] | 0 [0–1] | <0.001 | 0.003 |
| QoL: sleepa | 3 [0–6] | 5 [1.5–7] | 0 [0–3] | <0.001 | 0.003 |
| QoL: taste for livinga | 1 [0–4] | 1 [0–5] | 0 [0–1] | <0.001 | 0.003 |
| QoL total [HRQoL]: [0–70]a | 18 [6–34] | 22 [11–40] | 4 [0–14] | <0.001 | 0.003 |
| Global population | Patients with pain | Patients without pain | p | Adjusted p | |
|---|---|---|---|---|---|
| N | 200 | 151 [75.5] | 49 [24.5] | ||
| Anxiety score [0–21] | 7 [4–10] | 9 [6–11] | 4 [2–6] | <0.001 | 0.003 |
| Depression score [0–21] | 4 [2–8] | 5.5 [3–9] | 2 [1–3] | <0.001 | 0.003 |
| QoL: general activitya | 3 [1–6] | 4 [2–7] | 0 [0–3] | <0.001 | 0.003 |
| QoL: mooda | 3 [1–6] | 4 [1.5–6] | 0 [0–2] | <0.001 | 0.003 |
| QoL: ability to ambulatea | 1 [0–5] | 2 [0–6] | 0 [0–0] | <0.001 | 0.003 |
| QoL: usual worka | 3 [0–6] | 4 [1–7] | 0 [0–2] | <0.001 | 0.003 |
| QoL: relationship with othersa | 1.5 [0–5] | 2 [0–6] | 0 [0–1] | <0.001 | 0.003 |
| QoL: sleepa | 3 [0–6] | 5 [1.5–7] | 0 [0–3] | <0.001 | 0.003 |
| QoL: taste for livinga | 1 [0–4] | 1 [0–5] | 0 [0–1] | <0.001 | 0.003 |
| QoL total [HRQoL]: [0–70]a | 18 [6–34] | 22 [11–40] | 4 [0–14] | <0.001 | 0.003 |
Anxiety and depression were screened with the Hospital Anxiety and Depression [HAD] Scale.24
Each item of quality of life was rated on a scale 0–10 [0 = no impact].
Assessment of the total quality of life used the Health-Related Quality of Life [HRQoL] questionnaire [the sum of the scores for each item; score between 0 and 70].1 Adjusted p: adjusted p values using the method of Benjamini and Hochberg.
Impact of pain on anxiety, depression and quality of life [QoL]
| Global population | Patients with pain | Patients without pain | p | Adjusted p | |
|---|---|---|---|---|---|
| N | 200 | 151 [75.5] | 49 [24.5] | ||
| Anxiety score [0–21] | 7 [4–10] | 9 [6–11] | 4 [2–6] | <0.001 | 0.003 |
| Depression score [0–21] | 4 [2–8] | 5.5 [3–9] | 2 [1–3] | <0.001 | 0.003 |
| QoL: general activitya | 3 [1–6] | 4 [2–7] | 0 [0–3] | <0.001 | 0.003 |
| QoL: mooda | 3 [1–6] | 4 [1.5–6] | 0 [0–2] | <0.001 | 0.003 |
| QoL: ability to ambulatea | 1 [0–5] | 2 [0–6] | 0 [0–0] | <0.001 | 0.003 |
| QoL: usual worka | 3 [0–6] | 4 [1–7] | 0 [0–2] | <0.001 | 0.003 |
| QoL: relationship with othersa | 1.5 [0–5] | 2 [0–6] | 0 [0–1] | <0.001 | 0.003 |
| QoL: sleepa | 3 [0–6] | 5 [1.5–7] | 0 [0–3] | <0.001 | 0.003 |
| QoL: taste for livinga | 1 [0–4] | 1 [0–5] | 0 [0–1] | <0.001 | 0.003 |
| QoL total [HRQoL]: [0–70]a | 18 [6–34] | 22 [11–40] | 4 [0–14] | <0.001 | 0.003 |
| Global population | Patients with pain | Patients without pain | p | Adjusted p | |
|---|---|---|---|---|---|
| N | 200 | 151 [75.5] | 49 [24.5] | ||
| Anxiety score [0–21] | 7 [4–10] | 9 [6–11] | 4 [2–6] | <0.001 | 0.003 |
| Depression score [0–21] | 4 [2–8] | 5.5 [3–9] | 2 [1–3] | <0.001 | 0.003 |
| QoL: general activitya | 3 [1–6] | 4 [2–7] | 0 [0–3] | <0.001 | 0.003 |
| QoL: mooda | 3 [1–6] | 4 [1.5–6] | 0 [0–2] | <0.001 | 0.003 |
| QoL: ability to ambulatea | 1 [0–5] | 2 [0–6] | 0 [0–0] | <0.001 | 0.003 |
| QoL: usual worka | 3 [0–6] | 4 [1–7] | 0 [0–2] | <0.001 | 0.003 |
| QoL: relationship with othersa | 1.5 [0–5] | 2 [0–6] | 0 [0–1] | <0.001 | 0.003 |
| QoL: sleepa | 3 [0–6] | 5 [1.5–7] | 0 [0–3] | <0.001 | 0.003 |
| QoL: taste for livinga | 1 [0–4] | 1 [0–5] | 0 [0–1] | <0.001 | 0.003 |
| QoL total [HRQoL]: [0–70]a | 18 [6–34] | 22 [11–40] | 4 [0–14] | <0.001 | 0.003 |
Anxiety and depression were screened with the Hospital Anxiety and Depression [HAD] Scale.24
Each item of quality of life was rated on a scale 0–10 [0 = no impact].
Assessment of the total quality of life used the Health-Related Quality of Life [HRQoL] questionnaire [the sum of the scores for each item; score between 0 and 70].1 Adjusted p: adjusted p values using the method of Benjamini and Hochberg.
Impact of pain with central sensitization compared to without central sensitization on anxiety, depression and quality of life [QoL]
| Abdominal pain [all patients] | With central sensitization | Without central sensitization | p | Adjusted p | |
|---|---|---|---|---|---|
| N | 124 | 35 [28.2] | 89 [71.8] | ||
| Anxiety score [0–21] | 9 [6–11] | 9 [7.5–14] | 8 [6–11] | 0.04 | 0.076 |
| Depression score [0–21] | 5.5 [3–9] | 6 [4–11.5] | 5 [3–8] | 0.06 | 0.10 |
| QoL: general activitya | 5 [2–7] | 6 [4.5–8] | 4 [0–6] | <0.001 | 0.003 |
| QoL: mooda | 5 [2–6] | 6 [3.5–7] | 3 [0–6] | 0.01 | 0.023 |
| QoL: ability to ambulatea | 2 [0–6] | 5 [2–7] | 1 [0–4] | <0.001 | 0.003 |
| QoL: usual worka | 5 [2–7] | 7 [5–8] | 3 [1–6] | <0.001 | 0.003 |
| QoL: relationship with othersa | 3 [0–6] | 5 [3–6] | 2 [0–5] | <0.001 | 0.003 |
| QoL: sleepa | 5 [2–7] | 7 [4.5–8] | 4 [1–6] | <0.001 | 0.003 |
| QoL: taste for livinga | 1.5 [0–5] | 4 [1–7] | 1 [0–4] | 0.001 | 0.003 |
| QoL total [HRQoL]: [0–70]a | 23.5 [14–40] | 39 [26–49] | 18 [11–34] | <0.001 | 0.003 |
| Abdominal pain [all patients] | With central sensitization | Without central sensitization | p | Adjusted p | |
|---|---|---|---|---|---|
| N | 124 | 35 [28.2] | 89 [71.8] | ||
| Anxiety score [0–21] | 9 [6–11] | 9 [7.5–14] | 8 [6–11] | 0.04 | 0.076 |
| Depression score [0–21] | 5.5 [3–9] | 6 [4–11.5] | 5 [3–8] | 0.06 | 0.10 |
| QoL: general activitya | 5 [2–7] | 6 [4.5–8] | 4 [0–6] | <0.001 | 0.003 |
| QoL: mooda | 5 [2–6] | 6 [3.5–7] | 3 [0–6] | 0.01 | 0.023 |
| QoL: ability to ambulatea | 2 [0–6] | 5 [2–7] | 1 [0–4] | <0.001 | 0.003 |
| QoL: usual worka | 5 [2–7] | 7 [5–8] | 3 [1–6] | <0.001 | 0.003 |
| QoL: relationship with othersa | 3 [0–6] | 5 [3–6] | 2 [0–5] | <0.001 | 0.003 |
| QoL: sleepa | 5 [2–7] | 7 [4.5–8] | 4 [1–6] | <0.001 | 0.003 |
| QoL: taste for livinga | 1.5 [0–5] | 4 [1–7] | 1 [0–4] | 0.001 | 0.003 |
| QoL total [HRQoL]: [0–70]a | 23.5 [14–40] | 39 [26–49] | 18 [11–34] | <0.001 | 0.003 |
Anxiety and depression were screened with the Hospital Anxiety and Depression [HAD] Scale.24
Each item of quality of life was rated on a scale 0–10 [0 = no impact].
Assessment of the total quality of life used the Health-Related Quality of Life [HRQoL] questionnaire [score between 0 and 70].1 Comparisons were made between patients complaining of abdominal pain with central sensitization and without central sensitization. Adjusted p: adjusted p values using the method of Benjamini and Hochberg.
Impact of pain with central sensitization compared to without central sensitization on anxiety, depression and quality of life [QoL]
| Abdominal pain [all patients] | With central sensitization | Without central sensitization | p | Adjusted p | |
|---|---|---|---|---|---|
| N | 124 | 35 [28.2] | 89 [71.8] | ||
| Anxiety score [0–21] | 9 [6–11] | 9 [7.5–14] | 8 [6–11] | 0.04 | 0.076 |
| Depression score [0–21] | 5.5 [3–9] | 6 [4–11.5] | 5 [3–8] | 0.06 | 0.10 |
| QoL: general activitya | 5 [2–7] | 6 [4.5–8] | 4 [0–6] | <0.001 | 0.003 |
| QoL: mooda | 5 [2–6] | 6 [3.5–7] | 3 [0–6] | 0.01 | 0.023 |
| QoL: ability to ambulatea | 2 [0–6] | 5 [2–7] | 1 [0–4] | <0.001 | 0.003 |
| QoL: usual worka | 5 [2–7] | 7 [5–8] | 3 [1–6] | <0.001 | 0.003 |
| QoL: relationship with othersa | 3 [0–6] | 5 [3–6] | 2 [0–5] | <0.001 | 0.003 |
| QoL: sleepa | 5 [2–7] | 7 [4.5–8] | 4 [1–6] | <0.001 | 0.003 |
| QoL: taste for livinga | 1.5 [0–5] | 4 [1–7] | 1 [0–4] | 0.001 | 0.003 |
| QoL total [HRQoL]: [0–70]a | 23.5 [14–40] | 39 [26–49] | 18 [11–34] | <0.001 | 0.003 |
| Abdominal pain [all patients] | With central sensitization | Without central sensitization | p | Adjusted p | |
|---|---|---|---|---|---|
| N | 124 | 35 [28.2] | 89 [71.8] | ||
| Anxiety score [0–21] | 9 [6–11] | 9 [7.5–14] | 8 [6–11] | 0.04 | 0.076 |
| Depression score [0–21] | 5.5 [3–9] | 6 [4–11.5] | 5 [3–8] | 0.06 | 0.10 |
| QoL: general activitya | 5 [2–7] | 6 [4.5–8] | 4 [0–6] | <0.001 | 0.003 |
| QoL: mooda | 5 [2–6] | 6 [3.5–7] | 3 [0–6] | 0.01 | 0.023 |
| QoL: ability to ambulatea | 2 [0–6] | 5 [2–7] | 1 [0–4] | <0.001 | 0.003 |
| QoL: usual worka | 5 [2–7] | 7 [5–8] | 3 [1–6] | <0.001 | 0.003 |
| QoL: relationship with othersa | 3 [0–6] | 5 [3–6] | 2 [0–5] | <0.001 | 0.003 |
| QoL: sleepa | 5 [2–7] | 7 [4.5–8] | 4 [1–6] | <0.001 | 0.003 |
| QoL: taste for livinga | 1.5 [0–5] | 4 [1–7] | 1 [0–4] | 0.001 | 0.003 |
| QoL total [HRQoL]: [0–70]a | 23.5 [14–40] | 39 [26–49] | 18 [11–34] | <0.001 | 0.003 |
Anxiety and depression were screened with the Hospital Anxiety and Depression [HAD] Scale.24
Each item of quality of life was rated on a scale 0–10 [0 = no impact].
Assessment of the total quality of life used the Health-Related Quality of Life [HRQoL] questionnaire [score between 0 and 70].1 Comparisons were made between patients complaining of abdominal pain with central sensitization and without central sensitization. Adjusted p: adjusted p values using the method of Benjamini and Hochberg.
4. Discussion
Our study confirmed that 75% of IBD patients complained of pain. Abdominal pain was reported in 62% of patients. Furthermore, 25% of patients with abdominal pain reported pain with clinical presentation of central sensitization. In more than 50% of IBD patients, extra-intestinal manifestations also caused pain. CD as compared with UC was found to be an independent factor for pain. Pain significantly results in anxiety and depression and impairs quality of life. Central sensitization, more frequent in CD patients with severe disease, resulted in more intense pain and was associated with more severely impaired quality of life.
4.1. Pain with central sensitization characteristics
The originality of our study was its focus on the prevalence of pain with central sensitization characteristics in IBD patients with chronic abdominal pain and their consequences using both questionnaires and clinical examination. Chronic pain has recently been categorized as [i] nociceptive caused by damage to tissues, [ii] neuropathic caused by nerve damage, and [iii] nociplastic secondary to enhanced central nervous system [CNS] pain and sensory processing and altered pain modulation.7,8 Gastrointestinal pain can be nociceptive, neuropathic and nociplastic.11 Multiple aetiologies and components can coincide in an individual patient. The mechanisms and diagnosis of chronic gastrointestinal pain in IBD patients are therefore complex. Although nociplastic pain is identified as a unique category independent of tissue and somatosensory nerve damage, there is evidence for overlap of nociceptive, neuropathic and nociplastic pain.8 This suggests that nociplastic pain might not be a distinct entity, but instead part of a chronic pain continuum.8,9 Both neuropathic and nociplastic pain thus share common pathophysiological disturbances such as sensitization and neuroplastic changes, and so similar clinical presentations.8,11,14 All this makes it difficult to distinguish between neuropathic and nociplastic pain. Our study found abdominal pain with central sensitization characteristics in 17% of our IBD patients and in a quarter of the patients with abdominal pain. Pain intensity in these circumstances was generally reported as severe and to significantly impair quality of life. The prevalence of pain with central sensitization might have been greater if we had considered extra-abdominal pain. Indeed, in irritable bowel syndrome, extra-intestinal symptoms could result from central pain facilitation.14 We thus observed an association between central sensitization and extra-abdominal manifestation. Except for the severity of CD determined with the HBI we were unable to identify risk factors for abdominal pain with central sensitization.
Abdominal nociplastic pain in IBD patients can result from sensitization of the CNS, reorganization of brain centres involved in pain processing, and dysfunction in the descending pain modulatory system.11 A neuropathic component due to somatosensory nerve damage secondary to repeated bowel inflammatory reactions such as reported in chronic pancreatitis28 cannot be excluded. Referred pain, secondary to convergence of visceral and somatic nerve fibres on the same neuron in the dorsal horn of the spinal cord,11,14,29 could explain the occurrence of cutaneous hyperalgesia or hypo-aesthesia even with no history of abdominal surgery. Searching for central sensitization may be important to adapt treatment strategies. Although non-pharmacological treatments and psychological therapies remain a preferred first step in the treatment, the use of centrally acting drugs such as antidepressants and gabapentinoids might be considered and tested.5,8 None of our patients were prescribed antidepressants to treat pain.
4.2. Prevalence of pain
The high prevalence of pain in our study is consistent with data from other countries.1,30 Young age, female sex and CD are risk factors for pain. In our survey, pain was more frequent in CD than in UC, while others reported similar prevalence in both types of IBD.1 Our observation is, however, in agreement with the difference in the PRO2 questionnaires between CD patients and UC patients. Pain is included in the PRO2 questionnaire for CD patients but not for UC patients.20 This suggests that in contrast to CD patients, pain may not be a major complaint among UC patients, who typically present with bloody diarrhoea, bowel dysfunction and bowel movement problems. The differences between CD and UC patients reported in our study suggest a different pathophysiology of pain between these two types of IBD; greater transmural damage to the intestinal wall and more intense systemic inflammation in CD might contribute to these differences. These observations and hypotheses deserve further research.
4.3. Impact of pain on anxiety, depression and quality of life
This study found that pain was associated with anxiety, depression and impaired quality of life. Long-lasting pain results in decreased quality of life, increased pain medication use, and co-morbidities including depression, anxiety and even substance misuse.5,14,30 In addition, pain attacks seriously interfere with social and work activities. Central sensitization was associated with more severely impaired quality of life. The chronicity of the disease and the associated pain may cause patients to turn to healthcare resources. We note that anxiety and depression are also known to be risk factors for chronic pain.31 In this ‘chicken-and-egg’ situation, it is thus difficult to know whether the high scores of anxiety and depression reported by these patients are the cause or the effect of chronic pain.
4.4. Extra-intestinal pain
Our study confirms the high prevalence of extra-intestinal pain in IBD patients [>50%].4,32 Furthermore, almost three-quarters of patients with extra-intestinal manifestations reported abdominal pain. Extra-intestinal pain was mainly joint pain. These observations are important because rheumatic manifestations of IBD harm quality of life.32 The high prevalence of joint pain emphasizes the need for a multidisciplinary approach with a rheumatologist to determine the potential cause of joint pain: arthritis associated with IBD, degenerative joint disease independent of IBD, or functional pain without osteo-articular substrate but potentially secondary to pathophysiological changes of the nervous system and central sensitization.14,33 Such diagnosis can help select the best strategies and approaches to treat the IBD, its peripheral arthropathies and its pain.32,33 Our study did not enable us to separate these different types of joint pain.
4.5. Limitations of our study
Our study had several limitations. The DN4 questionnaire was one of the items to diagnose and define central sensitization. This questionnaire has been validated for neuropathic pain but not for nociplastic pain. However, the diagnosis of central sensitization also relied on data from the clinical examination [cutaneous hyperalgesia] and the pain descriptors used by patients. We measured the prevalence of extra-intestinal manifestations, mainly joint pain, but did not differentiate the different potential aetiologies of rheumatic pain. When we planned our study, our main purpose was to explore abdominal pain in IBD patients, both gastrointestinal and parietal, the pathophysiology of which is complex and remains poorly understood. Our questionnaires and clinical examination therefore focused on the abdominal region. The high prevalence of pain in patients attending a specialist IBD outpatient clinic may differ from IBD patients in daily practice. However, our findings are similar to results of others.1 The high rate of patients with active disease might surprise and be explained by several factors: potential recruitment bias of patients during consultation of E.L. focusing on more serious and complicated patients; recruitment during the COVID crisis, which might have discouraged less ill patients from coming to the clinic; and definition of active disease according to the HBI and Mayo scores whose medians are low in our study, suggesting that many of our patients presented with only mild active disease. We performed multiple comparisons between patients with and without pain, and between patients with and without central sensitization. The p values were therefore adjusted using the Benjamini–Hochberg mthod. As all the comparisons may not be considered independent, this technique could be considered even as being too conservative, which strengthens our conclusions. Finally, our study failed to identify independent risk factors for pain associated with central sensitization except for the severity of CD. Our study may have been underpowered for determining potential risk factors.
5. Conclusions
Our study demonstrates that the prevalence of pain, both abdominal and extra-intestinal, mainly joint pain, is high in IBD patients and at least partly disconnected from the activity of the disease. Consequently, quality of life is harmed. Pain with central sensitization occurs in a quarter of patients with abdominal pain. In this case, pain is more severe and impairs the quality of life even more intensely. Although we do not know whether they are the causes or the effects of pain, anxiety and depression scores were also higher in these patients. The difficulty managing pain associated with central sensitization and the high prevalence of rheumatic pain complicate pain management in IBD patients and should therefore prompt a multidisciplinary approach with pain medicine specialists and rheumatologists.
Funding
This work was supported by the Department of Anaesthesiology, CHU Liège, Belgium.
Conflict of Interest
All the authors declare they have no competing interests linked to this work.
Acknowledgments
We thank Prof. Patricia Lavandhomme [Anaesthesioloy and Pain Clinic, Cliniques Universitaires Saint-Luc, Brussels] and Dr Clio Ribbens [Rheumatology, CHU Liège] for their relevant comments.
Author Contributions
P.Y.H. contributed to study design, patient recruitment, data collection, statistical analysis and data analysis. J.F. contributed to patient recruitment, data collection and data analysis. D.L. contributed to study design and data analysis. E.L. contributed to study design, patient recruitment and data analysis. J.J. contributed to study design, statistical analysis, data analysis and first draft of the paper. Presented at the annual meeting of the French Society of Anaesthesia and Reanimation [SFAR] in Paris, 23 September 2021.
Data Availability
The data used in this study are available to download at the following link: [https://drive.google.com/drive/folders/1gUpyrcjF5WFn7s0GDEreBMJuoHeKHcwO?usp=sharing].
