Startseite Medizin Symptoms of central sensitization in patients with inflammatory bowel diseases: a case-control study examining the role of musculoskeletal pain and psychological factors
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Symptoms of central sensitization in patients with inflammatory bowel diseases: a case-control study examining the role of musculoskeletal pain and psychological factors

  • Carrie Falling EMAIL logo , Simon Stebbings , G David Baxter , Corey A Siegel , Richard B Gearry , Jo Nijs und Ramakrishnan Mani
Veröffentlicht/Copyright: 28. Oktober 2020
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Scandinavian Journal of Pain
Aus der Zeitschrift Scandinavian Journal of Pain Band 21 Heft 2

Abstract

Objectives

Musculoskeletal (MSK) pain is a common complaint in patients with inflammatory bowel diseases (IBD). MSK pain in IBD has previously demonstrated association with symptoms of central sensitization; however it is uncertain whether these symptoms are influenced simply by the presence of MSK pain and/or IBD. Primary aim of this study was to investigate whether symptoms of central sensitization differed across three groups: IBD patients with and without MSK pain and healthy controls. Secondary aim was to investigate between-group differences for measures of somatosensory functioning.

Methods

Cross-sectional study was performed on adults with IBD. Assessments included: central sensitization inventory (CSI), pressure pain threshold, temporal summation, conditioned pain modulation, perceived stress, affect style, anxiety, depression, and pain catastrophizing. One-way analyses of variance and covariance were used to investigate between-group differences for measures of central sensitization and potential confounding by psychological factors.

Results

Study participants (n=66) were age/gender matched across three study groups. Between-group differences were solely demonstrated for CSI scores [F(2,63)=19.835, p<0.001, r=0.62], with IBD patients with MSK pain demonstrating the highest CSI scores and healthy controls the lowest. After controlling for individual psychological features, post hoc comparisons indicated that CSI scores were significantly different between-groups (p≤0.025) after controlling for most psychological variables, with the exception of perceived stress (p=0.063) and pain catastrophizing (p=0.593).

Conclusions

IBD patients as a whole demonstrated significantly greater symptoms of central sensitization compared to healthy controls. However, IBD patients with persistent MSK pain demonstrated the greatest symptoms of central sensitization compared to patients without MSK pain and healthy controls. Between-group differences for CSI in IBD patients with MSK were not confounded by psychological features.

Implications

Study results indicate that persistent MSK pain in IBD represents patients with greater central sensitization symptomology. This increased symptomology is suggestive of underlying mechanisms related to central sensitization, highlighting patient potentially at risk for worse pain experiences.

Keywords: central sensitization; inflammatory bowel disease; musculoskeletal pain

Introduction

Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are chronic inflammatory conditions of the gastrointestinal tract resulting from dysregulated immune responses [1], [2], [3], [4]. Pain is reported to affect over 70% of individuals with IBD, where abdominal and musculoskeletal (MSK) pain represent the most common complaints [5], [6], [7], [8], [9]. Similar to other chronic inflammatory diseases, MSK pain in IBD may be influenced by multiple clinical features of both pain and IBD [9], [10], [11].

Inflammatory processes and/or injuries have been shown to trigger changes within the central nervous system, termed central sensitization, which can lead to pain hypersensitivity seen in persistent pain states [12], [13], [14], [15]. Specifically, the International Association for the Study of Pain (2017) defines central sensitization as an increase in responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input. The numerous and complex pathophysiological mechanisms attributed to central sensitization, including pain facilitation, inhibition, and sensory processing [14], are reported to result in worse pain experiences in patient populations [16], [17], [18].

Our recent investigation exploring the multidimensional nature of persistent MSK pain in IBD characterized three clinically relevant subgroups, where individuals with worse MSK pain experiences presented with active IBD and symptoms related to central sensitization [11], [19]. These results highlighted the relationship between features of MSK pain and IBD to symptoms of central sensitization. However, this investigation was conducted only on individuals with both IBD and MSK pain, therefore it is unclear whether study results were influenced simply by the presence of MSK pain and/or the presence of IBD itself.

Clinical assessment of central sensitization utilizes diagnostic surrogate markers to, for instance examine various clinical and experimental characteristics related to symptomology, somatosensory functioning, and factors (e.g. lifestyle and psychological) influencing pain perceptions [14], [20], [21]. The pathophysiological mechanisms of central sensitization are believed to be responsible for the overlapping clinical features of central sensitivity syndromes (CSSs), such as fibromyalgia, chronic fatigue, irritable bowel syndrome, and temporomandibular joint disorder [21], [22]. It has been proposed that the symptoms of these conditions can be considered not as belonging to individual disorders, but as different manifestations of a common underlying mechanism (i.e. central sensitization) [21]. This viewpoint led to the development of symptomatic screening tools, such as the central sensitization inventory (CSI), to broadly assess overlapping dimensions of CSSs and quantify the degree of central sensitization symptomatology [21].

In addition to symptomology, assessment of somatosensory functioning is widely used to evaluate perceptual responses to systematically applied sensory stimuli, in an effort to characterize function or dysfunction within sensory pathways, including investigation of pressure pain thresholds (PPT), temporal summation (TS) and conditioned pain modulation (CPM) [20], [23]. Likewise, psychological factors, such as mood disorders and psychological distress, have been identified as important determinants of pain experiences in both acute and chronic conditions [24], [25], [26], [27]. As a result, evaluation of cognitive and affective features are commonly used to explore the modulation of pain perceptions, as well as somatosensory assessments [25]. Previous investigation of persistent MSK pain profiles in IBD indicated that the presence of mood disorders were strongly associated with MSK pain profiles in IBD [11]. However, the potentially confounding roll of such psychological factors to assessment of central sensitization constructs in IBD is still unknown.

To address this knowledge gap, the primary aim of the present study was to investigate whether symptoms related to central sensitisation, assessed by the CSI, differed across three groups: IBD patients with MSK pain, IBD patients without MSK pain, and healthy controls. Similarly, the secondary aim was to investigate between-group differences for somatosensory assessments (i.e., PPT, CPM, and TS). Finally, the present study investigated whether potential between-group differences are confounded by psychological factors (i.e. perceived stress, affect style, anxiety, depression, and pain catastrophizing). It was hypothesized that IBD patients with MSK pain will demonstrate greater symptoms of central sensitization (i.e. higher CSI scores) and altered somatosensory functioning (i.e. PPT, CPS, and TS) compared to IBD patients without pain, and to healthy controls. It was further hypothesized that psychological factors will demonstrate a degree of confounding in the measures of central sensitization found to be significantly different between the study groups described above.

Methods

The present cross-sectional study was conducted and reported according to the STROBE guidelines for observational studies [28]. This study was granted ethical approval by the Institutional Review Board for Dartmouth College, Committee for the Protection of Human Subjects (STUDY00031471).

Participants

From February to July of 2019, individuals aged 18 years or older presenting to the IBD Center of Dartmouth-Hitchcock Medical Center (DHMC) were invited to participate across three age/gender matched study groups: (1) IBD with MSK pain, (2) IBD without MSK pain, and (3) healthy controls. Patients with a previously established and documented IBD diagnosis by a gastroenterologist were identified through the DHMC’s electronic medical records with written approval obtained by each treating physician prior to all recruitment efforts. Healthy controls were recruited through email invitations to DHMC staff members and friends/family members of identified patients.

Exclusion criteria

IBD patients (with and without MSK pain) were excluded if they reported any of the following: pregnancy, history of drug (i.e. illicit or prescription) and/or alcohol abuse, any condition resulting in altered sensation such as: nerve injuries, neurological conditions (e.g. stroke, multiple sclerosis, and Parkinson’s disease), or surgery within the last 3 months. Where feasible, the inclusion/exclusion criteria for healthy controls were based on the expert consensus guidelines for investigations utilizing quantitative sensory testing [29]. Participants meeting inclusion/exclusion criteria were invited to attend one examination session at DHMC. Participants were provided with detailed information related to the study and written consent was obtained in accordance with the Declaration of Helsinki.

Data collection

Data collection included one session per participant, which was conducted in the same private examination room located at DHMC. Sessions included somatosensory testing, followed by completion of digitized questionnaires. The order of somatosensory testing was standardized, whereas the order of questionnaires was randomized to reduce test order effects, with skip patterns to direct participants toward relevant questionnaires where applicable. Outcome measures used during the examination session are presented in Table 1. Following the examination sessions, data extraction from the patients’ medical records was performed to characterize IBD features.

Table 1:

Outcome measures used to features of central sensitization, IBD, and pain.

Domain Outcome measure
Primary outcomes
 Central sensitization symptoms Central Sensitization Inventory (part A)
 Somatosensory assessments

  • Pressure pain threshold

  • Conditioned pain modulation

  • Temporal summation
Secondary outcomes
 Psychological factors

  • Hospital anxiety and depression scale

  • Perceived stress scale (10-item)

  • Positive and negative affective schedule

  • Pain catastrophizing scale
 Health-related quality of life

  • Short inflammatory bowel disease questionnaire

  • EuroQoL five-dimensional questionnaire
 Abdominal pain

  • PROMIS pain interference 4a

  • Numeric rating scale (severity)
 Musculoskeletal pain

  • Regional location (body diagram)

  • PROMIS pain interference 4a

  • Numeric rating scale (severity)
 Sleep quality Pittsburgh sleep quality index (single item)
 Total comorbidity score

  • Self-administered comorbidity questionnaire

  • Extra-intestinal manifestation checklist

  • Central sensitization inventory (part B)

  1. IBD, Inflammatory bowel disease; and PROMIS, Patient-Reported Outcomes Measurement Information System.

Demographic, lifestyle, and comorbidity features

Participant demographics included: age, gender, and ethnicity. Lifestyle factors assessed included: smoking status, alcohol consumption, cannabis use, and sleep quality. Sleep quality was assessed using a single item of the Pittsburgh Sleep Quality Index [30], where participants were asked to respond to the question: During the past month, how would you rate your sleep quality overall? (Very good, fairly good, fairly bad, and very bad). Total comorbidity scores were calculated as disease counts using health conditions identified on the Self-Administered Comorbidity Questionnaire [31], a 20-item extra-intestinal manifestation (EIM) checklist developed from multiple EIM investigations [32], [33], [34], [35], and conditions identified on part B of the central sensitization inventory (CSI).

Overall health-related quality of life was assessed using the EuroQoL five-dimensional (EQ-5D) questionnaire [36]. The EQ-5D questionnaire descriptive system comprises five domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each one with five possible levels: no problems (level 1), slight problems (level 2), moderate problems (level 3), severe problems (level 4), and extreme problems (level 5), as well as a visual analogue scale ranging from 0 to 100.

Psychological features

Psychological features examined included: anxiety/depression, perceived stress, affect style, and pain catastrophizing. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). Correlation between subscales (anxiety and depression) of HADS and the internal consistency of the subscales were found to be strong with Cronbach’s α values of 0.83 and 0.82, respectively [37]. Scores for each subscale range from 0 to 21, with a score of ≥8 representing clinically meaningful levels of anxiety or depression [37]. Scores for the entire scale (emotional distress) range from 0 to 42, with higher scores indicating more distress.

Perceived stress in the present study was explored through the 10-item Perceived Stress Scale (PSS-10). The PSS-10 evaluates the degree to which individuals believe their life has been unpredictable, uncontrollable, and overloaded during the previous month, using a Likert scale (0–4) for each item [38]. A review of the psychometric evidence for the PSS-10 indicated good internal consistency and test-retest reliability with coefficients reaching >0.70 in all cases [39]. PSS-10 scores can range from 0 to 40 with higher scores indicating higher perceived stress [38]. Categorical interpretation of PSS-10 scoring, includes: low stress (0–13), moderate stress (14–26), and high stress (27–40).

Affect style in the present study was explored through the Positive and Negative Affective Schedule (PANAS). This scale includes words describing 10 positive and 10 negative emotions, and requires participants to indicate on a Likert scale (1–5) the extent to which they felt each emotion during the previous week. Items included in PANAS were designed to allow independent positive and negative scoring, in acknowledgement that having, for instance, a low negative affect does not equate to having a high positive affect [40]. PANAS subscales demonstrated very high correlation (α=0.89–0.95) with their corresponding regression-based factor analysis scores, whereas the discriminant correlations (α=−0.02–−0.18) were quite low [40]. Similarly, reliability of the positive (α=0.86) and negative (α=0.87) subscales were found to be high, while correlation between the scales (α=−0.09) remained low.

Pain catastrophizing in the present study was explored through the Pain Catastrophizing Scale (PCS). This measure assesses three different domains of pain catastrophizing, including rumination, magnification, and helplessness [41]. Participants are asked to indicate the degree to which they experience various thoughts and feelings when they are in pain using Likert scales ranging from (0) ‘not at all’ to (4), with total possible scores ranging from 0 to 52 [41]. Clinically relevant levels of pain catastrophizing are identified as PCS scores >30. The Cronbach alpha values reported for the total PCS (α=0.87) were found to be satisfactory and acceptable [41]. Evidence for convergent validity was demonstrated with moderate correlation of the PCS to scores on self-report measures of anxiety (r=0.32; p<0.001) and negative affect (r=0.32; p<0.001).

IBD characteristics

The following IBD features were characterised in the present study: IBD subtype (Crohn’s disease, ulcerative colitis, or indeterminate colitis), duration, medication use, abdominal pain, and disease course.

Medication use in IBD participants included consideration of previous and current use of steroids, biologics, and immunosuppressants. Abdominal pain was evaluated in terms of interference and severity. Abdominal pain interference was evaluated through Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference 4a short form, developed by the National Institutes of Health [42]. PROMIS short forms have undergone extensive qualitative expert and patient review, as well as quantitative analysis of data collected on general populations and clinical samples [42]. Positive findings for abdominal pain interference include: mild (50–59), moderate (60–69), or severe (≥70). Abdominal pain severity was evaluated using numeric rating scales recorded for worst, average, and current pain levels, with positive findings as mild (1–4), moderate (5–6), or severe (7–10) [43].

Disease course was assessed including: previous surgery, history of a stoma, age at diagnosis, disease behaviour, disease extent, and health-related quality of life [44], [45]. The Montreal classification system was used to describe phenotypes of IBD [46], to include: age at diagnosis (≤16 years old, 17–40 years old, and >40 years old), disease behaviour (penetrating, stricturing, and/or perianal disease), and disease extent. Disease extent for Crohn’s disease was defined as limited disease (<40 cm ileal involvement or absence of pancolitis) or extensive disease (ileal involvement of at least 40 cm or presence of pancolitis) [45]. Disease extent for ulcerative colitis was defined as limited disease (distal to the splenic flexure) or extensive disease (beyond the splenic flexure) [45], [47].

Health-related quality of life was assessed using the validated Short IBD Questionnaire (SIBDQ) [44], [48]. SIBDQ demonstrated significant retest reliability (ICC=0.65, Cronbach’s α=0.78) with ability to detect clinically meaningful changes in health-related quality of life through the assessment of five health dimensions (bowel symptoms, systemic symptoms, functional impairment, social impairment, and emotional function) [48]. SIBDQ score ranges from 10 (poor health-related quality of life) to 70 (optimum health-related quality of life), with scoring interpreted as poor (10–29), moderate (30–49), and optimal (50–70).

MSK Pain characteristics

Characteristics of MSK pain evaluated in the present study included: location, duration, interference, and severity. Pain location was recorded regionally (n=47) using a body diagram, which previously demonstrated significant test-retest reliability (r=0.85) in chronic pain patients [6], [9], [49]. Individuals with multiple pain regions were instructed to identify their “main” area of pain. Assessments of MSK pain interference and severity related to an individual’s “main” area of pain, using PROMIS Pain Interference 4a and numeric rating scales, respectively. Positive findings for the PROMIS Pain Interference 4a, include: mild (50–59), moderate (60–69), or severe (≥70). Numeric rating scales for pain severity were recorded for worst, average, and current pain levels, with positive findings as mild (1–4), moderate (5–6), or severe (7–10) [43].

Features of central sensitization

Surrogate markers of central sensitization utilized in the present study included investigation of symptomology (i.e. CSI) and somatosensory functioning (i.e. PPT, CPM, and TS).

Symptoms of central sensitization

CSI has been validated to investigate an array of symptoms and risk factors associated with central sensitization and central sensitivity syndromes, within the domains of physical, emotional distress, headache/jaw, and urological features [21]. CSI (part A) evaluates 25 features across an array of somatic and emotional symptoms, with each item scored on a scale of 0–4, and overall scoring ranging from 0 to 100 [50]. Higher CSI scores indicate increased symptomology related to central sensitization, with scores ≥40 indicating the likely presence of central sensitivity syndromes [21], [51]. The use of CSI as an indirect measure of central sensitization has been validated previously (AUC=0.86, Sensitivity=81%, Specificity=75%) in a large population with central sensitivity syndromes [21], [51].

Somatosensory assessments

Sensory testing conditions

All three study groups underwent the same standardized examination protocol, performed by a single investigator (CF). This investigator received training by a senior investigator (RM) for all testing procedures. Testing was performed in a quiet room, with participants positioned in comfortable prone lying for PPT and in supine for screening assessments, TS, and CPM. All participants were provided a trial of each assessment to familiarize themselves with the procedure at remote body locations before data collection was initiated.

Screening assessments

Screening assessments used to detect the presence of peripheral neuropathies in the present study included Semmes-Weinstein monofilament examination (SWME) [52], [53] and vibration detection threshold (VDT) [54]. The SWME demonstrated high sensitivity (93.1%) and specificity (100%) for identifying decreased sensation confirmed by gold standard nerve conduction tests [52]. SWME of the upper limb was performed using a 4.56 (4 g) monofilament at six locations divided over the palm and fingers, bilaterally [55]. SWME of the lower limb was performed using a 5.07 (10 g) monofilament at the pulp of the great toe, as well as the first, third, and fifth metatarsal heads, bilaterally [52]. VDT was assessed using a Rydel–Seiffer graded tuning fork (64 Hz, 8/8 scale) placed over bony prominences (styloid process of the ulna and medial malleolus), bilaterally. Participants were instructed to verbally indicate the moment they could no longer feel the sensation of vibration, and this value was recorded. VDT of each site was described as the mean of three trials [56].

Pressure pain threshold

PPT was assessed at Tibialis anterior (5 cm distal to the Tibial tuberosity), using an electronic handheld algometer (Wagner Force One™ FDIX), by a series of three ascending stimulus intensities with a 60 s interval between trials. Each stimulus was given as a slowly increasing ramp (approximately 50 kPa/s) from 0 to a maximum pressure of 1000 kPa [56], [57]. If the participant did not indicate pain at 1000 kPa, this value was considered as the PPT. Participants were instructed to verbally stop the test when the sensation of pressure alone changed to one of pressure and pain, with the corresponding pressure recorded for each trial. PPT for was described as the mean of three trials, where lower scores indicated greater pain sensitivity. PPT has previously demonstrated strong discriminative validity between chronic pain patients and healthy controls (OR=0.10; 95% CI 0.04–0.24), p<0.001) [58]. Specifically, PPT at the Tibialis anterior muscle demonstrated excellent intra-examiner reliability (ICC=0.91; 95% CI 0.31–0.95) [59].

Conditioned pain modulation

Assessment of CPM was performed immediately following the assessment of PPT described above. PPT of Tibialis anterior was used as the test stimulus and a standardized ice bath to the contralateral hand as the conditioning stimulus. The magnitude of the CPM effect in the present study was defined as the percent change score between PPT after compared to before the conditioning stimulus. A higher CPM change score suggested greater pain modulation and the participant is said to be a CPM responder. CPM has previously demonstrated positive evidence of test–retest reliability and agreement using PPT and an ice bath as test and conditioning stimulus, respectively [60].

Pressure stimulation

PPT on Tibialis anterior was performed as described above, prior to and immediately following the conditioning stimulus.

Conditioning stimulus

Participants were asked to submerge their hand contralateral to the test site (Tibialis anterior), wide open and up to the wrist, in a container of circulating ice water, for a maximum of 2 min. The temperature of the ice water was maintained below 3 °C, monitored by a thermometer with a digital display [57], [61], [62]. Participants were instructed to withdraw their hand when the pain perceived became intolerable or when the 2 min maximum was reached. Participants were asked to give a numeric pain rating (0–10) at the time of hand removal. Total immersion time and pain rating of the conditioning stimulus were recorded.

Mechanical temporal summation

Mechanical TS was assessed on the volar aspect of the non-dominant arm using a Semmes-Weinstein monofilament (no. 6.65) [63]. The perceived intensity of a single stimulus was compared with that of a series of 10 repetitive stimuli of the same physical intensity (1/s applied within an area of 1 cm2) [56]. Participants were asked to give a pain rating for the single stimulus and a pain rating for the series of 10 stimuli as a whole, using a ‘0–10’ numerical rating scale. This procedure was repeated for three trials, with 1 minute between trials, and performed at different areas of the volar forearm for each trial. Mechanical TS in the present study was defined as the percent change score between the mean pain rating of 10 series and the mean pain rating of the single stimuli. Higher percent change scores indicated greater TS, indicating an increased gain or facilitation into the CNS. Assessments of TS have previously demonstrated positive evidence of test–retest reliability and agreement [60], with strong discriminative validity between chronic pain patients and healthy controls (OR=0.30; 95% CI 0.17–0.54), p<0.001) [58].

Sample size

A priori sample size estimation for the present study was based on the mean and standard deviation (SD) of the CSI in healthy populations (primary aim) [21], [51], [64], [65]. Given the available data, total sample size of n=51 was estimated as able to demonstrate between group differences at 80% power and 5% level of significance.

Statistical Analysis

All statistical analyses were performed using IBM SPSS Statistics (version 26). Descriptive statistics were used to characterize IBD, pain, psychological, demographic, comorbidity, lifestyle, and measures of central sensitization evaluated in the present study. Where appropriate, Chi-square/Fisher’s exact tests (categorical variables) and independent t-tests (continuous variables) were used to characterize differences between the two IBD groups with regards to IBD features. Similarly, where appropriate, Chi-square/Fisher’s exact tests (categorical variables) and one-way analyses of variance (ANOVAs)/Kruskal-Wallis ANOVAs (continuous variables) were used to characterize differences between the three groups for psychological, demographic, lifestyle, and comorbidity features. Significance was identified at p≤0.05.

ANOVAs/Kruskal-Wallis ANOVAs were used to investigate between-group differences for the CSI as the primary aim, and somatosensory assessments (PPT, CPM, and TS) as the secondary aim of the current study. Assumptions for all ANOVA models were assessed to ensure model fit, including: normality of scoring distribution (Shapiro–Wilk tests) and homoscedasticity (scatterplot of residuals). Post hoc tests were conducted for each measure of central sensitization reaching significance at p≤0.05. Bonferroni corrections for significance (p≤0.016) were used for a total of 3 pairwise comparisons (between IBD without MSK pain and healthy controls; IBD with MSK pain and healthy controls; IBD without MSK pain and IBD with MSK pain).

Univariate analyses of covariance (ANCOVAs) were used to investigate potential confounding by psychological features to the measures of central sensitization demonstrating significant between-group differences (p≤0.05). Additional assumptions for ANCOVAs were explored, including tests of normality listed above and Levene’s test for homogeneity.

Results

A total of 77 individuals (53 IBD patients and 24 healthy controls) volunteered to participate in the study. Of the patients with IBD, 24 reported no history of MSK pain and 29 reported the presence of MSK pain lasting longer than 3 months within the past year. None of the IBD patients nor the healthy controls were indicated as having features of peripheral neuropathy during screening assessments (i.e. SWME and VDT). However, two IBD patients were later diagnosed with neurological conditions and were therefore excluded from the present analysis. Similarly, 2 healthy controls were excluded due to a diagnosis of diabetes mellitus. With the exception of one participant representing an 8 year age gap, the remaining participants were age (±5 years) and gender matched across the following three study groups: IBD patients with MSK pain (n=22), IBD patients without MSK pain (n=22), and healthy controls (n=22).

Demographics, comorbidity, and lifestyle factors

Demographic, lifestyle, and comorbidity status of the study participants are presented in Table 2. Participants represented the following ethnic groups, with one participant identifying with two groups: White (n=63), African American (n=1), and Asian American (n=3).

Table 2:

Participant characteristics across the three study groups (n=66).

Characteristic IBD with MSK pain (n=22) IBD without MSK pain (n=22) Healthy controls (n=22) p-Value
Gender –
 Male, n (%) 10 (45) 10 (45) 10 (45)
 Female, n (%) 12 (55) 12 (55) 12 (55)
Age –
 Range (years) 18–68 21–67 19–59
 Mean (SD) 37.64 (11.50) 37.95 (12.97) 37.73 (11.12)
Total comorbidity
 Range (n) 1–6 0–5 0
 Mean (SD) 3.14 (1.73) 1.68 (1.52) 0
Smoking (yes, n (%)) 1 (5) 1 (5) 0 (0)
Alcohol consumption
 Yes, occasionally 12 (55) 13 (59) 16 (73) 0.019a*
 Yes, regularly 2 (9) 5 (23) 6 (27)
 No 8 (36) 4 (18) 0 (0)
Cannabis use (yes, n (%)) 9 (41) 4 (18) 2 (9) 0.048b*
Poor sleep quality 10 (45) 4 (18) 0 (0) 0.012a*
EuroQol-5D-5L
 Total (mean (SD)) 7.29 (1.62) 5.45 (0.74) 5.41 (0.80) <0.001c*
 VAS (mean (SD)) 70.48 (20.55) 83.64 (11.40) 89.91 (8.33) <0.001c*

  1. IBD, Inflammatory bowel disease; MSK, musculoskeletal; SD, standard deviation; EuroQol-5D-5L, health-related quality of life questionnaire; and VAS, visual analogue scale.aFisher’s exact test.bChi-squared.cKruskal–Wallis analysis of variance.*Significant at p≤0.05.

IBD features

A summary of IBD features observed in the current study are presented in Tables 3 and 4. No significant differences were found between the two IBD groups for any of the observed IBD features.

Table 3:

IBD features of study participants across two study groups (n=44).

Assessment IBD with MSK pain (n=22) IBD without MSK pain (n=22) p-Value
IBD subtype 0.901a
 Crohn’s disease (n (%)) 11 (50) 13 (59)
 Ulcerative colitis (n (%)) 9 (41) 7 (32)
 Indeterminate colitis (n (%)) 2 (9) 2 (9)
IBD duration, years (mean (SD)) 13.77 (10.47) 14.45 (10.38) 0.985b
 Range 1–42 2–41
Surgical history, yes (n (%)) 10 (45) 8 (36) 0.540c
SIBDQ 51.50 (6.47) 55.77 (9.38) 0.355b
Abdominal pain (n (%)) 13 (59) 7 (32) 0.069c
 Severity (NRS) (mean (SD)) 4.23 (2.09) 2.57 (2.51)
 PROMIS Pain interference 4a (mean (SD)) 57.30 (9.51) 53.26 (12.79)
Medications
 Steroids (n (%)) 0.318c
  Never

  Previous		 3 (14)

17 (77)		 8 (36)

12 (55)
  Current use 2 (9) 2 (9)
 Biologic (n (%)) 0.414c
  Never 1 (5) 4 (18)
  Previous 2 (9) 2 (9)
  Current 19 (86) 16 (73)
 Immunosuppressant (n (%)) 0.602c
  Never 13 (59) 10 (45)
  Previous 7 (32) 8 (36)
  Current 2 (9) 4 (18)

  1. IBD, Inflammatory bowel disease; MSK, musculoskeletal; SD, standard deviation; SIBDQ, Short Inflammatory Bowel Disease Questionnaire; NRS, numeric rating scale; and PROMIS, Patient-Reported Outcomes Measurement Information System.

  2. aFisher’s exact test.

  3. bIndependent t-test.

  4. cChi-squared.

  5. *Significant at p≤0.05.

Table 4:

Montreal classification of two study groups (n=44).

Characteristic IBD with MSK pain (n=22) IBD without MSK pain (n=22) p-Value
Age at diagnosis (n (%)) 0.056a
 ≤16 years old 8 (36) 3 (14)
 17–40 years old 12 (55) 18 (82)
 >40 years old 2 (9) 0 (0)
Location (n (%)) –
 Crohn’s disease
  Terminal ilium 4 (31) 2 (13)
  Colon 4 (31) 3 (20)
  Ileocolon 5 (38) 9 (60)
 Ulcerative colitis
  Proctitis 1 (11) 1 (14)
  Left-sided 0 (0) 2 (29)
  Extensive 8 (89) 5 (71)
Behaviour (n (%)) 1.000a
 Stricturing 3 (14) 3 (14)
 Penetrating 4 (18) 5 (23)
 Both stricturing/penetrating 3 (14) 3 (14)
 Perianal 9 (41) 8 (36)

  1. IBD, Inflammatory bowel disease; and MSK, musculoskeletal.

  2. aFisher’s exact test.

  3. *Significant at p≤0.05.

Musculoskeletal pain features

Of the participants reporting the presence of MSK pain, 59.1% (n=13) also reported the presence of abdominal pain. All of the IBD patients with MSK pain reported the presence of more than one painful region (range=2–17, mean (SD)=8.32 (4.61)). Of the MSK regions identified as painful by study participants, the low back (n=11, 50.0%) and mid back (n=11, 50.0%) were the most frequently reported regions, while the posterior neck (n=4, 18.2%) was most frequently identified as the ‘main area of pain’. Numeric rating scales for pain severity relevant to the ‘main area of pain’ included: strongest pain severity (range=0–9, mean (SD)=4.86 (2.55)) and average pain severity (range=0–7, mean (SD)=3.14 (2.05)). PROMIS Pain Interference 4a scores relevant to the ‘main area of pain’ ranged from 41.6 to 66.6 (mean (SD)=53.83 (7.54)).

Psychological features

Psychological features of the study participants are presented in Table 5. The majority of participants in both IBD groups (n=12, 54.5%) demonstrated moderate levels of perceived stress, while the majority of healthy controls (n=14, 63.6%) demonstrated mild perceived stress. Only one IBD patient without MSK pain reached a clinically meaningful score (>30) of pain catastrophizing. HADS subscales indicated that 45.4% (n=10) of IBD patients with MSK pain demonstrated clinically meaningful scores (≥8) for the presence of anxiety, whereas only 13.6% (n=3) of these same patients demonstrated clinically meaningful scores (≥8) for depression. Conversely, 18.2% (n=4) of IBD patients without MSK pain and 18.2% (n=4) of healthy controls demonstrated clinically meaningful scores for anxiety, with no IBD patients without MSK pain and 5.5% (n=1) of the healthy controls demonstrating clinically meaningful scores for depression.

Table 5:

Psychological features across three study groups (n=66).

Assessment IBD with MSK pain

Mean (SD)		 IBD without MSK pain

Mean (SD)		 Healthy controls

Mean (SD)		 p-Value
HADS
 Anxiety 7.59 (3.97) 6.05 (3.08) 5.45 (3.58) 0.175a
 Depression 4.05 (3.44) 2.73 (2.12) 2.50 (2.60) 0.226a
10-PSS 15.55 (7.58) 13.55 (7.35) 10.18 (5.88) 0.043b*
PANAS

 Positive affect		 31.05 (6.19) 33.95 (7.38) 35.86 (5.70) 0.052b
 Negative affect 19.18 (6.90) 16.27 (4.23) 16.18 (3.70) 0.270a
PCS 8.76 (7.53) 7.45 (9.26) 1.95 (2.98) 0.001a*

  1. IBD, Inflammatory bowel disease; MSK, musculoskeletal; SD, standard deviation; HADS, Hospital Anxiety and Depression Scale; PSS, 10-item Perceived Stress Scale; PANAS, Positive and Negative Affective Schedule; and PCS, Pain Catastrophizing Scale.

  2. aKruskal–Wallis analysis of variance.

  3. bOne-way analysis of variance.

  4. *Significant at p≤0.05.

Features of central sensitization

A summary of participant scores for CSI, PPT, CPM, and TS are presented in Table 6. CSI scores were normally distributed (Shapiro–Wilk, p≥0.05), with an overall range of 3 to 56 in study participants. Within the three study groups, 45.4% (n=10) of IBD patients with MSK pain demonstrated benchmarked CSI scores (≥40) representing patients with the likely presence of central sensitivity syndromes. Conversely, 18.2% (n=4) of patients without MSK pain and no healthy controls demonstrated benchmarked CSI scores. PPT was normally distributed (Shapiro–Wilk, p≥0.05), with an overall range of 118.01–754.13 kPa in study participants. CPM and TS were not normally distributed (Shapiro–Wilk, p<0.05) within study groups. CPM scores ranged from −43% to 185%, and TS scores ranged from 0% to 4% in study participants.

Table 6:

Measures of central sensitization across three study groups (n=66).

Measure IBD with MSK pain

Mean (SD)		 IBD without MSK pain

Mean (SD)		 Healthy controls

Mean (SD)		 One-way ANOVA/Kruskal–Wallis
CSI 36.86 (9.63) 26.23 (12.68) 17.05 (8.58) F(2,63)=19.84, p<0.001*
PPTa 381.94 (178.77) 398.77 (174.17) 450.05 (171.50) F(2,63)=0.91, p=0.409
TSb 100 [54–146] 133 [100–200] 100 [62–144] H(2)=2.67, p=0.263
CPMb,c 20 [8–29] 29 [13–47] 24 [16–30] H(2)=3.13, p=0.209

  1. IBD, Inflammatory bowel disease; MSK, musculoskeletal; SD, standard deviation; ANOVA, analysis of variance; CSI, central sensitization inventory; PPT, pressure pain threshold; TS, temporal summation; and CPM, conditioned pain modulation.

  2. aValues represent raw scoring for measures.

  3. bValues represent percent change for dynamic somatosensory measures.

  4. cMedian [interquartile range].

  5. *Significant at p≤0.05.

Between-group comparisons

Results for one-way ANOVAs to examine between-group differences for measures of central sensitization are summarised in Table 6. There was a statistically significant difference between groups for mean CSI scores (F(2,63)=19.835, p<0.001, r=0.62) with an observed power of greater than 90%. A Bonferroni corrected post hoc test revealed that mean CSI scores were significantly (p≤0.016) different between groups (mean difference ± standard error, [95% confidence intervals]), including IBD patients with MSK pain compared to without MSK pain (10.64±3.15, [2.89, 18.38], p=0.004), IBD patients with MSK pain compared to healthy controls (19.82±3.15, [12.07, 27.56], p<0.001), and IBD patients without MSK pain compared to healthy controls (9.18±3.15, [1.44, 16.93], p=0.015). There were no statistically significant differences between group means for remaining measures of central sensitization, including: PPT of Tibialis anterior (F(2,63)=0.906, p=0.409), CPM (H(2)=2.671, p=0.263), and TS (H(2)=3.129, p=0.209).

Results for one-way ANCOVAs comparing CSI scores between study groups while controlling for individual psychological features are presented in Table 7. There was a significant difference in mean CSI scores between study groups when individually controlling for PSS (F(2,62)=15.445, p<0.001, r=0.75), PANAS (positive) (F(2,62)=15.058, p<0.001, r=0.71), PANAS (negative ) (F(2,62)=15.058, p<0.001, r=0.75), HADS (anxiety) (F(2,62)=18.173, p<0.001, r=0.73), HADS (depression) (F(2,62)=18.978, p<0.001, r=0.76), and PCS and F(2,55)=12.488, p<0.001, r=0.78). Post hoc comparisons indicated an observed power of greater than 90% for all models, with decreased mean CSI differences between IBD patients with and without MSK pain, as well as healthy controls after controlling for most psychological variables. Mean differences for adjusted CSI scores reached significance (p≤0.05) with the exception of between IBD patients without MSK pain and healthy controls (p=0.063 and p=0.593, respectively) after controlling for PSS and PCS.

Table 7:

Mean differences for central sensitization inventory scores between three study groups adjusted for psychological features.

CSI Model summary IBD with MSK pain compared to IBD without MSK pain IBD with MSK pain compared to healthy controls IBD without MSK pain compared to healthy controls
MD (SE), [95% CI] p-Value MD (SE), [95% CI] p-Value MD (SE), [95% CI] p-Value
Unadjusted r=0.62, F(2,63)=19.84, p<0.001* 10.64 (3.15), [2.89, 18.38] 0.004* 19.82 (3.15), [12.07, 27.56] <0.001* 9.18 (3.15), [1.44, 16.93] 0.015*
Adjusted
 PSS r=0.75, F(2,62)=15.45, p<0.001* 9.01 (2.68), [2.41, 15.62] 0.004* 15.46 (2.80), [8.57, 22.35] <0.001* 6.45 (2.72), [−0.243, 13.14] 0.063
 PANAS-positive r=0.71, F(2,62)=15.06, p<0.001* 8.60 (2.91), [1.44, 15.76] 0.013* 16.44 (3.00), [9.07, 23.82] <0.001* 7.84 (2.88), [0.75, 14.94] 0.025*
 PANAS-negative r=0.75, F(2,62)=18.17, p<0.001* 7.45 (2.75), [0.69, 14.21] 0.026* 16.53 (2.75), [9.76, 23.31] <0.001* 9.08 (2.68), [2.50, 15.66] 0.004*
 HADS-anxiety r=0.73, F(2,62)=17.25, p<0.001* 8.41 (2.81), [1.50, 15.33] 0.012* 16.74 (2.85), [9.73, 23.76] <0.001* 8.33 (2.77), [1.51, 15.15] 0.011*
 HADS-depression r=0.76, F(2,62)=18.98, p<0.001* 7.82 (2.67), [1.26, 14.38] 0.014* 16.52 (2.69), [9.91, 23.13] <0.001* 8.70 (2.62), [2.26, 15.14] 0.004*
 PCS r=0.78, F(2,55)=12.49, p<0.001* 10.56 (2.81), [3.63, 17.49] 0.001* 14.17 (2.95), [6.88, 12.47] <0.001* 3.61 (2.77), [−3.23, 10.45] 0.593

  1. CSI, Central sensitization inventory; IBD, inflammatory bowel disease; MSK, musculoskeletal; SE, standard error; PSS, perceived stress scale; PANAS, positive and negative affect schedule; HADS, hospital anxiety and depression scale; and PCS, pain catastrophizing scale.

  2. *p≤0.05.

Discussion

The present study investigated differences for symptoms of central sensitization (i.e. CSI) as the primary aim and somatosensory assessments (PPT, CPM, and TS) as the secondary aim, between three groups: IBD patients with and without MSK pain and healthy controls. Analysis indicated that CSI demonstrated a significant difference between study groups, whereas none of the somatosensory assessments reached significance. Investigation of confounding factors for between-group differences demonstrated a significant influence on CSI scores from all of the psychological features explored in the present study. However, CSI scores remained significantly different between all study groups even after controlling for psychological confounding, with the exception of perceived stress and pain catastrophizing. Models controlling for PSS and PCS demonstrated that mean CSI scores were no longer significantly different between IBD patients without MSK pain and healthy controls.

The between-group differences for CSI scoring seen in current results are similar to previous findings [11], where the presence of persistent MSK pain demonstrated greater symptoms of central sensitization (higher CSI scores). The literature reports similar findings, with higher CSI scoring in chronic MSK pain patients when compared to healthy controls [21], [66]. A study exploring subpopulations of MSK pain (i.e. fibromyalgia, chronic widespread pain, and chronic regional low back pain) showed that all MSK pain types presented with greater symptoms of central sensitization compared to healthy controls [21]. However, in addition to MSK pain, the between-group differences for CSI scoring in the current study indicate that the presence of IBD independent of MSK pain was also associated with higher CSI scoring. These results highlight the need for further investigation to understand the relationship between IBD and symptoms of central sensitization outside of MSK pain experiences.

The present study did not demonstrate significant differences in somatosensory assessments (i.e. PPT, CPM, and TS) between the three study groups. These results suggest that altered somatosensory functioning may not be a major contributing factor in persistent MSK pain experiences in IBD patients. However, the construct of somatosensory functioning may be more complex than simply explained by the presence of IBD and/or MSK pain. Current literature suggests somatosensory assessments may be influenced by additional features, such as differences in pain presentations [67], [68]. Previous studies investigating a variety of discrete pain types, including neuropathic conditions, fibromyalgia, and chronic back pain, have indicated that different conditions present with different somatosensory profiles [67], [68]. Similarly, different neurological conditions demonstrated a mixed profile of altered somatosensory functioning, suggesting that somatosensory assessments vary within as well as between pain types [68]. Therefore, the diversity of MSK pain types represented in the present study may have contributed to variability in somatosensory assessments, resulting in a lack of statistical difference between the current study groups.

Influences from various lifestyle factors to somatosensory assessments have been documented for both pain and healthy populations [29], [69], [70]. An ongoing challenge of investigations utilizing current somatosensory assessments relates not only to identifying, for instance lifestyle factors which influence assessments but also in recruiting healthy participants across demographic spectrums which adhere to the strict inclusion criteria of current guidelines, such as sleep disturbances [29]. Although the present study attempted to closely follow these guidelines, strict adherence was not feasible. Therefore, results may reflect influences from similar additional factors across all study groups, thus contributing to the variability in somatosensory assessments. However, less restrictive inclusion criteria increases the generalizability of study results.

Similarly, IBD groups in the current study did not significantly differ with regards to any of the observed IBD features, to include the presence of abdominal pain. As such, study results are unable to determine whether the presence of abdominal pain influenced somatosensory assessments and contributed to the variability of these measures. However, stratifying study participants by the presence of abdominal pain is problematic in IBD populations, as abdominal pain is a well-understood consequence of active disease. Controlling for abdominal pain in this manner may reduce the generalizability of study results solely to IBD patients in remission. Future research should explore the association of somatosensory assessments to clinically active IBD alongside the presence of abdominal pain, to better understand the contribution of these factors.

Although central sensitization has been proposed in the generation and maintenance of chronic abdominal and post-surgical pain in IBD patients, [71], [72], [73], there have been few investigations of somatosensory functioning in IBD [74], [75]. A previous investigation reported no difference in PPT and TS of bilateral dorsum of the hand between Crohn’s disease patients and healthy controls [74]. However, the authors did not report on factors known to influence somatosensory assessments, such as psychological and lifestyle factors, as well as the use of biologic therapies, which are a recognized cause of peripheral neuropathy (i.e. altered somatosensory functioning) in IBD patients [76], [77].

The influences of psychological features on CSI scoring in the present study are similar to previous reports in the literature. Psychometric validation of CSI indicated that psychological factors, such as anxiety and depression, accounted for over 7% of the variance in CSI scoring and consequently have been identified as one of the four primary domains of this measure [21]. As such, the confounding relationship demonstrated by HADS sub-scores in the present study may be conceptually problematic due to the likely overlap to known psychological constructs explored in the CSI. However, the contribution of other psychological factors explored in the present study (i.e. affect style, perceived stress, and pain catastrophizing) represent constructs beyond those potentially captured in CSI scoring. Thus current study results suggest that although these additional constructs demonstrated a degree of confounding, the relationship between greater symptoms of central sensitization and the presence of MSK pain and IBD cannot be explained by these psychological factors alone, therefore implicating participation from other CSI domains.

CSI was developed with the intention of producing a screening assessment to identify patients whose presenting symptoms may be related to an underlying presence of central sensitization [21], [64]. CSI explores features of psychological distress, sleep disturbances, fatigue, pain, and hyperalgesia/allodynia (i.e. visceral and somatic) in order to quantify the sensitivity of the somatosensory system [21], [22], [66], [78]. Therefore, in addition to psychological features, interpretation of current study results within the domains of CSI would suggest that IBD patients with and without MSK pain may demonstrate a greater influence from features such as sleep quality, multiple pain sources (i.e. abdominal and MSK), as well as visceral hypersensitivity (i.e. functional bowel changes). Future research should explore the contributions of additional patient features to overall CSI scores in order to better understand the nature of central sensitivity in IBD patients.

As previously described, CSI is understood to be an assessment of symptoms attributed to mechanisms of central sensitization. Despite the fact that CSI is unable to objectively confirm the presence of such mechanisms, the use of CSI has been promoted in chronic pain algorithms as a method of identifying the need for further mechanistic investigation, such as assessments of somatosensory functioning [79], [80]. Therefore, although the present study did not identify differences in somatosensory assessments across the study groups, the fact that CSI scores were significantly higher in IBD patients, increasingly so in those with MSK pain presentations, supports continued investigation of central mechanisms in this population. However, future research should employ methodologies to account for the variability in somatosensory measures, such as investigation of targeted MSK pain subtypes, as well as an exploration of influences from additional participant features (e.g. lifestyle and IBD features).

Although the present study achieved the stated a priori sample size, this estimate was based on calculations to detect between-group differences for CSI scores as the primary study aim. As a result, the present sampling may have not been sufficient to detect between-group differences for somatosensory assessments (second study aim) resulting in a Type 2 error for these measures. Additionally, as the sample size requirements necessary to include multiple covariates in an ANCOVA model are substantial, the present study aimed to solely explore the contributions of individual psychological variables. As such, future research should explore the combined influence of the different psychological constructs to CSI scores in order to better understand the overall contribution of psychological features in this population.

Somatosensory assessments in the current study did not include the full battery of quantitative sensory testing. Therefore, interpretation of somatosensory functioning in the current study relates only to PPT, TS, and CPM performed at specified body regions. Future investigations of somatosensory assessment in IBD patients with and without MSK pain could consider additional body regions and other sensory modalities, such as thermal and pain tolerance thresholds.

Conclusion

The present study is the first to investigate differences in measures of central sensitization between IBD patients with and without MSK pain, and healthy controls. Study results indicate that IBD patients demonstrated significantly greater symptoms of central sensitization compared to healthy controls. Furthermore, results indicated that the presence of persistent MSK pain in IBD demonstrated the greatest magnitude of central sensitization symptoms compared to patients without MSK pain and healthy controls. Finally, the present study suggests that the relationship between greater symptoms of central sensitization and the presence of MSK pain and IBD cannot be explained by psychological functioning alone.

Corresponding author: Carrie Falling, PhD, School of Physiotherapy, University of Otago, 325 Great Kings Street, Dunedin, 9010, New Zealand. Phone: +644797460, Mobile: +6421558513, E-mail:

Acknowledgments

Ms Damara Crate, IBD Research Nurse (DHMC) and Dr Jenna Koliani-Pace, MD (DHMC) are acknowledged for their support during the data collection phase of this study. Prior to publication, author C.F. was a fulltime University of Otago PhD candidate and acknowledges receipt of a University of Otago doctoral scholarship and Alumni of University of Otago in America, MacGibbon PhD Travel Fellowship.

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent has been obtained from all individuals included in this study.

  5. Ethical approval: This research complies with all the relevant national regulations, institutional policies and was performed in accordance with the tenets of the Helsinki Declaration, and has been approved by Institutional Review Board for Dartmouth College, Committee for the Protection of Human Subjects.

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Received: 2020-07-01
Accepted: 2020-09-04
Published Online: 2020-10-28
Published in Print: 2021-04-27

© 2020 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Salami-slicing and duplicate publication: gatekeepers challenges
  4. Editorial Comment
  5. Risk for persistent post-delivery pain – increased by pre-pregnancy pain and depression. Similar to persistent post-surgical pain in general?
  6. Systematic Review
  7. Acute experimentally-induced pain replicates the distribution but not the quality or behaviour of clinical appendicular musculoskeletal pain. A systematic review
  8. Topical Review
  9. Unwillingly traumatizing: is there a psycho-traumatologic pathway from general surgery to postoperative maladaptation?
  10. Clinical Pain Research
  11. Translation, cross-cultural adaptation and psychometric evaluation of the Thai version of the fear-avoidance beliefs questionnaire in patients with non-specific neck pain
  12. Pain management in patients undergoing radiation therapy for head and neck cancer – a descriptive study
  13. Do intensity of pain alone or combined with pain duration best reflect clinical signs in the neck, shoulder and upper limb?
  14. Different pain variables could independently predict anxiety and depression in subjects with chronic musculoskeletal pain
  15. Symptoms of central sensitization in patients with inflammatory bowel diseases: a case-control study examining the role of musculoskeletal pain and psychological factors
  16. Acceptability of psychologically-based pain management and online delivery for people living with HIV and chronic neuropathic pain: a qualitative study
  17. Determinants of pain occurrence in dance teachers
  18. Observational Studies
  19. A retrospective observational study comparing somatosensory amplification in fibromyalgia, chronic pain, psychiatric disorders and healthy subjects
  20. Utilisation of pain counselling in osteopathic practice: secondary analysis of a nationally representative sample of Australian osteopaths
  21. Effectiveness of ESPITO analgesia in enhancing recovery in patients undergoing open radical cystectomy when compared to a contemporaneous cohort receiving standard analgesia: an observational study
  22. Shoulder patients in primary and specialist health care. A cross-sectional study
  23. The tolerance to stretch is linked with endogenous modulation of pain
  24. Pain sensitivity increases more in younger runners during an ultra-marathon
  25. Original Experimental
  26. DNA methylation changes in genes involved in inflammation and depression in fibromyalgia: a pilot study
  27. Participants with mild, moderate, or severe pain following total hip arthroplasty. A sub-study of the PANSAID trial on paracetamol and ibuprofen for postoperative pain treatment
  28. Exploring peoples’ lived experience of complex regional pain syndrome in Australia: a qualitative study
  29. Although tapentadol and oxycodone both increase colonic volume, tapentadol treatment resulted in softer stools and less constipation: a mechanistic study in healthy volunteers
  30. Educational Case Report
  31. Updated management of occipital nerve stimulator lead migration: case report of a technical challenge
https://doi.org/10.1515/sjpain-2020-0109
Schlagwörter für diesen Artikel
central sensitization; inflammatory bowel disease; musculoskeletal pain

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Salami-slicing and duplicate publication: gatekeepers challenges
  4. Editorial Comment
  5. Risk for persistent post-delivery pain – increased by pre-pregnancy pain and depression. Similar to persistent post-surgical pain in general?
  6. Systematic Review
  7. Acute experimentally-induced pain replicates the distribution but not the quality or behaviour of clinical appendicular musculoskeletal pain. A systematic review
  8. Topical Review
  9. Unwillingly traumatizing: is there a psycho-traumatologic pathway from general surgery to postoperative maladaptation?
  10. Clinical Pain Research
  11. Translation, cross-cultural adaptation and psychometric evaluation of the Thai version of the fear-avoidance beliefs questionnaire in patients with non-specific neck pain
  12. Pain management in patients undergoing radiation therapy for head and neck cancer – a descriptive study
  13. Do intensity of pain alone or combined with pain duration best reflect clinical signs in the neck, shoulder and upper limb?
  14. Different pain variables could independently predict anxiety and depression in subjects with chronic musculoskeletal pain
  15. Symptoms of central sensitization in patients with inflammatory bowel diseases: a case-control study examining the role of musculoskeletal pain and psychological factors
  16. Acceptability of psychologically-based pain management and online delivery for people living with HIV and chronic neuropathic pain: a qualitative study
  17. Determinants of pain occurrence in dance teachers
  18. Observational Studies
  19. A retrospective observational study comparing somatosensory amplification in fibromyalgia, chronic pain, psychiatric disorders and healthy subjects
  20. Utilisation of pain counselling in osteopathic practice: secondary analysis of a nationally representative sample of Australian osteopaths
  21. Effectiveness of ESPITO analgesia in enhancing recovery in patients undergoing open radical cystectomy when compared to a contemporaneous cohort receiving standard analgesia: an observational study
  22. Shoulder patients in primary and specialist health care. A cross-sectional study
  23. The tolerance to stretch is linked with endogenous modulation of pain
  24. Pain sensitivity increases more in younger runners during an ultra-marathon
  25. Original Experimental
  26. DNA methylation changes in genes involved in inflammation and depression in fibromyalgia: a pilot study
  27. Participants with mild, moderate, or severe pain following total hip arthroplasty. A sub-study of the PANSAID trial on paracetamol and ibuprofen for postoperative pain treatment
  28. Exploring peoples’ lived experience of complex regional pain syndrome in Australia: a qualitative study
  29. Although tapentadol and oxycodone both increase colonic volume, tapentadol treatment resulted in softer stools and less constipation: a mechanistic study in healthy volunteers
  30. Educational Case Report
  31. Updated management of occipital nerve stimulator lead migration: case report of a technical challenge
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