Prevalence and Significance of Central Sensitization Syndrome in Patients With IBS

Multiple studies indicate that IBS overlaps with functional dyspepsia and gastroesophageal reflux disease more than expected by chance, and the overlap group experiences more severe symptoms and a greater impairment of quality of life.^1-3 While gastroenterologists are also aware that IBS commonly is co-morbid with anxiety and depression,¹ what is less well recognized is the overlap of IBS with several other extra-intestinal diseases. It has been hypothesized these overlapping conditions may cluster together because of central nervous system allodynia (neuropathic pain from a stimulus that does not normally provoke pain) or hyperalgesia that involves multiple organ systems, referred to as the central sensitization syndrome (CSS).

Wang et al conducted a cross-sectional study of primary care patients in the Mayo Clinic Health System. All had a diagnosis of IBS, fibromyalgia, and/or migraine; therefore, this was a selected outpatient population, not a random community sample. Of those who responded to a survey (15% of 5000 invites), one-third had a diagnosis of IBS. A number of diagnoses aside from IBS were asked about, including fibromyalgia, migraine, fatigue, temporomandibular pain, neck pain, restless legs syndrome, and chemical sensitivity. It was observed that symptom severity significantly increased and quality of life decreased as the number of comorbid conditions increased.

It was striking that very few of the patients surveyed by Wang et al had “isolated” IBS (3%); most had comorbid migraine, depression, anxiety, and/or fibromyalgia (each overlapping with IBS in more than 50% of cases). Nearly 20% with IBS had six or more comorbid diagnoses. However, this result likely reflects selection bias; the remarkably high rate of migraine and fibromyalgia for example almost certainly is because the entry criteria included these conditions as part of the cohort! As there was no outpatient control group, it’s also unclear how many of these conditions overlapped with IBS more than expected by chance.

The problem with the central sensitization syndrome hypothesis is it neglects other now well-recognized comorbid conditions in patients with IBS that seem unlikely to be explained through just increased pain sensitivity. For example, it is now established asthma and autoimmune diseases are comorbid with IBS (and functional dyspepsia).⁴ It has been suggested these associations reflect immune activation as an underlying mechanism, which could account for a number of other comorbidities too including muscle pains, fatigue, anxiety, and depression.^1,5 The overlap of IBS with pathological acid reflux is also not well explained by the central sensitization syndrome hypothesis.¹

There is a growing appreciation IBS is a systemic disorder in most cases, and not an isolated intestinal syndrome. A comprehensive understanding of comorbidity in IBS is important because of the relevance to optimizing management outcomes. Wang et al add new knowledge around these poorly understood overlapping conditions, but we are not convinced the central sensitization syndrome hypothesis neatly explains all comorbidity in IBS.

References

1. Talley NJ. What Causes Functional Gastrointestinal Disorders? A Proposed Disease Model. Am J Gastroenterol. 2020;115(1):41-44. https://journals.lww.com/ajg/Abstract/2020/01000/What_Causes_Functional_Gastrointestinal_Disorders_.10.aspx
2. Jones MP, Shah A, Walker MM, et al. Overlap of heartburn, functional dyspepsia, and irritable bowel syndrome in a population sample: Prevalence, temporal stability, and associated comorbidities. Neurogastroenterol Motil. 2022;34(9):e14349. https://onlinelibrary.wiley.com/doi/10.1111/nmo.14349
3. von Wulffen M, Talley NJ, Hammer J, et al. Overlap of Irritable Bowel Syndrome and Functional Dyspepsia in the Clinical Setting: Prevalence and Risk Factors. Dig Dis Sci. 2019;64(2):480-486. https://link.springer.com/article/10.1007/s10620-018-5343-6
4. Koloski N, Jones M, Walker MM, et al. Population based study: atopy and autoimmune diseases are associated with functional dyspepsia and irritable bowel syndrome, independent of psychological distress. Aliment Pharmacol Ther. 2019;49(5):546-555. https://onlinelibrary.wiley.com/doi/full/10.1111/apt.15120
5. Burns GL, Talley NJ, Keely S. Immune responses in the irritable bowel syndromes: time to consider the small intestine. BMC Med. 2022;20(1):115. https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-022-02301-8