Pain in Patients with Crohn’s and Colitis: Can We Solve the Puzzle?

Pain is frequent in gastrointestinal disorders. In outpatient settings, complaints about abdominal pain are about four times higher than for the second most prevalent symptoms.¹ Pain is also frequent in inflammatory bowel diseases [IBD]. Hence, in a Swiss cohort, 71% of patients experienced pain during the course of disease, and 49% with ulcerative colitis [UC] and 55% with Crohn’s disease [CD] reported pain as a long-standing problem. Pain in UC is generally intermittent and associated with exacerbations of the disease, whereas patients with CD often have persistent pain due to complications such as strictures of the bowel, fistulas, persistent ulcerations and irreversible changes of the pain system [see below].

Pain in IBD is often misclassified. The reason for this is that many clinicians compare abdominal pain with the somatic pain they know from personal experience. However, visceral pain is very different from its somatic counterpart and is typically diffuse, associated with autonomic symptoms [that may dominate the clinical picture], referred to remote somatic structures, and accompanied by increased sensations from other organs. The neurophysiological basis for these differences is well described in both animal and human studies [for a review see^2]. The consequences of the complex neuroanatomy may blur the diagnoses. For example, electrical stimulation of the ileo-caecum, where CD is predominantly localized, can result in referred pain located in the left abdomen.³ A confounding factor is that pain may change when the peritoneum is involved. A typical example is acute appendicitis, where pain initially is diffusely localized in the abdomen [and autonomic symptoms such as sweating and nausea may dominate the clinical picture]. However, when the inflammation becomes transmural and the peritoneum [which has a somatic nerve supply] is affected, the pain becomes distinct, corresponding to McBurney’s point. It also changes in character from diffuse and unpleasant to somatic-like [sharp and distinct]. Such changes in pain presentation can also be seen in IBD during progression of the disease.

The pathophysiology of pain in IBD patients can be linked to: [1] local factors related to inflammation; [2] factors related to the peripheral, autonomic [including enteric] and central nervous systems, and [3] factors indirectly related to IBD. Local inflammation and its complications such as fistulas, abscesses and stenosis of the gut can obviously give pain, which is documented in preclinical and human studies.⁴ Pain location and intensity can change over time depending of factors such as those related to the inflammatory process and tissue tension. However, pain may not only be related to inflammation. In a previous paper we found that patients with active UC had hypersensitivity to experimental distension of the rectum, but they also had increased tone of the smooth muscles. As pain thresholds returned to normal during pharmacological myorelaxation, the muscles probably play a major role in pain pathophysiology during exacerbation of UC.⁵ The nervous system is also involved in painful IBD. Peripheral nerves may become sensitized during the acute inflammation, and due to local reflexes this may affect the enteric nervous system, resulting in motility changes that can be painful themselves, such as in ileus.² The increasing barrage from sensitized peripheral nerves may also result in central nervous system sensitization, where neuronal hyperexcitability and malfunctioning of normal pain-inhibitory systems predominate. In some patients this sensitization may persist despite normalization of the peripheral triggers, typically associated with cognitive and affective symptoms such as anxiety and depression. In patients with CD, increased somatic referred pain areas and abnormal anal reflexes to rectal distension have been found, probably reflecting central sensitization.⁶ On the other hand, in UC we found no pain augmentation to repeated rectal stimulations that is normally a proxy of central sensitization.⁵ Hence, patients with CD may be subject to persistent afferent neuronal barrage to the central nervous system due to the more severe transmural inflammation as well as complications. In patients with irreversible central sensitization, this may explain the continuing symptoms, although the gut pathology normalizes.² Finally, in many patients factors indirectly related to IBD may explain the symptoms, including small bacterial overgrowth, complications to previous surgery such as neuropathic pain from scars, opioid-induced bowel dysfunction and mesenteric ischaemia.² It should also be noted that joint pain and other extraintestinal complications to IBD are often painful, although they seldom result in abdominal pain.

In the current issue of this journal, Hardy and co-workers report on a prospective and cross-sectional study of 200 IBD patients. The strength of the study is that the same two gastroenterologists examined the patients, and a combination of physical examinations and questionnaires was used to assess pain in a systematic way at the bedside. As in previous studies, about 60% had abdominal pain, although referral bias may partly explain the findings. Furthermore, nearly 30% of patients with abdominal pain had evidence for central sensitization defined as [1] allodynia and hyperalgesia to testing of the abdomen with a Von Frey filament, [2] ‘neuropathic words’ used to describe the pain and [3] a score from a specific questionnaire suggesting a neuropathic pain origin. These patients had higher pain intensity, more breakthrough pain, higher disease activity and a lower quality of life compared with patients without ‘clinical central sensitization’. A substantial proportion reported extra-abdominal pain. As central sensitization was associated with these extraintestinal symptoms, it might be hypothesized that the pain threshold is lowered due to the pre-existing IBD and subsequent central sensitization. The authors should be acknowledged for using a systematic approach to pain assessment, and the study may pave the road for further studies where comprehensive and systematic quantitative sensory bedside testing is used to assess pain, such as has been done in chronic pancreatitis.⁷

Optimal pain management in IBD patients should of course target the underlying inflammation or complications. However, when this is not possible, symptomatic treatment of pain needs to be multidisciplinary [for details the reader is referred to^8]. Phenotyping pain such as shown by Hardy et al. may lead to a better understanding and diagnosis of the individual patients and potentially lead to targeted treatment of painful IBD.

Funding

None.

Conflicts of Interest

None.

References