Chronic Pain in the Inflammatory Bowel Disease Setting: An Undertreated and Inherently Complex Problem

Aug 1, 2021, 18:00 PM by Sherwin Barvarz, MD, Yale School of Medicine

 


Cite as: Barvarz S. Chronic pain in the setting of inflammatory bowel disease: an undertreated and inherently complex problem. ASRA News 2021;46. https://doi.org/10.52211/asra080121.049.
 

 

Inflammatory bowel disease (IBD)—a broad term used to describe a number of chronic inflammatory gastrointestinal (GI) conditions, most commonly ulcerative colitis and Crohn’s disease—is a potentially devastating diagnosis. Many patients with IBD experience acute and chronic abdominal pain with major implications on their quality of life and psychosocial well-being.1,2

Acute IBD flares trigger abdominal pain when inflammation activates afferents in the gastrointestinal tract. However, up to 20% of IBD patients in both clinical and endoscopic remission with no clinical evidence of inflammation may continue to experience abdominal pain.1 Studies have shown that 30%–50% of IBD patients experience chronic pain (i.e., pain occurring every day for three months or intermittently for six months).3,4

Mechanisms of Chronic Pain with IBD

The chronic, visceral abdominal pain that develops with IBD is linked to the hypersensitivity of primary sensory neurons in the GI tract and higher-order sensory neurons in the central nervous system (CNS). Decreased activity in descending CNS inhibitory control mechanisms may also play a role.1 Because emotional and psychological stress may affect the quality or degree of chronic pain, some patients experience irritable bowel syndrome-related symptoms as well.1,5 Other mechanisms of chronic pain with IBD include strictures, which may be a cause of persistent pain in the absence of inflammation, and small intestinal bacterial overgrowth, triggered by dysmotility secondary to postinflammatory changes.5

Pharmacologic and Procedural Treatment Modalities 

Evidence for effective treatment modalities for both acute and chronic pain with IBD is scarce. Of further concern is the fact that opioid use is more prevalent with IBD than any other chronic GI condition, and IBD-related pain is not improved during hospitalization, despite significant opioid treatment.2

Because acute pain occurs secondary to inflammation in IBD, inducing remission through standard IBD treatment regimens (e.g., corticosteroids, immunomodulators) is the standard of care.5 Managing IBD-related chronic pain is more complex, given the many possible mechanisms for each patient’s pain and the relative lack of evidence for effective treatment. Nonsteroidal anti-inflammatory agents have been studied with controversial results, with some researchers linking the agents to increased IBD flares.6 Antibiotics may help patients with suspected small intestinal bacterial overgrowth.7 Although randomized, controlled trials have been limited, antidepressants such as tricyclic antidepressants and selective serotonin reuptake inhibitors are suggested treatments for chronic IBD pain, particularly in patients with comorbid anxiety and depression.8

In addition to the various pharmacologic treatments proposed, procedural treatments have been studied as well. Although the efficacy of neurolytic blocks (e.g., celiac plexus block) have not been evaluated with randomized, controlled trials specifically with IBD patients, other neuromodulation treatments have been evaluated.5

A pilot study published in 2020 evaluated the use of vagus nerve stimulation over one year; seven of the nine patients achieved reduced pain scores.9 However, vagus nerve stimulators are currently approved only for refractory epilepsy and depression. Spinal cord stimulation, another neuromodulation technique, has demonstrated utility in many refractory pain states, with evidence supporting its use in chronic visceral abdominal pain.10

Finally, transcranial direct current stimulation (tDCS) has shown some promise in treating chronic IBD pain. Researchers theorize that it causes cortical and subcortical changes in the neuronal networks that mediate and modulate pain, reducing pain perception.11,12 A double-blind randomized controlled trial evaluating tDCS involved tDCS or sham treatment to the primary motor cortex in 20 IBD patients with chronic abdominal pain for 20 minutes per day over five days.12 Patients who received the intervention had significantly lower pain scores that continued one week after treatment. This was in the absence of any effect of tDCS on inflammatory markers, thus further exemplifying the centrally mediated nature of chronic abdominal pain in IBD.12

Conclusion

Chronic pain secondary to IBD is common and often present in the absence of endoscopic or clinical evidence of active inflammation. It has significant effects on patients’ quality of life and social and functional outcomes.4 However, effective treatment appropriate for most patients remains elusive because of the dearth of evidence comparing the efficacy of various treatments for chronic abdominal pain in IBD.

The opioid epidemic is another particular concern: although IBD patients are more likely to use opioids than those with any other chronic GI condition, studies have shown that they have limited efficacy.2 Neuromodulation is a promising frontier.9-12 Further studies are needed to the nature and development of chronic pain in IBD and to systematically evaluate and compare various treatment modalities.


Dr. Sherwin Barvarz
Sherwin Barvarz, MD, is a Clinical Fellow in Pain Medicine at Yale School of Medicine in New Haven, CT.

References

  1. Bielefeldt K, Davis B, Binion DG. Pain and inflammatory bowel disease. Inflamm Bowel Dis 2009;15(5):778–88. https://doi.org/10.1002/ibd.20848
  2. Berry SK, Takakura W, Bresee C, et al. Pain in inflammatory bowel disease is not improved during hospitalization: the impact of opioids on pain and healthcare utilization. Dig Dis Sci 2020;65(6):1777–83. https://doi.org/10.1007/s10620-019-05906-x
  3. Szigethy E. Pain management in patients with inflammatory bowel disease. Gastroenterol Hepatol 2018;14(1):53–6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824598/
  4. Morrison G, Van Langenberg DR, Gibson SJ, et al. Chronic pain in inflammatory bowel disease: characteristics and associations of a hospital-based cohort. Inflamm Bowel Dis 2013;19(6):1210–7. https://doi.org/10.1097/mib.0b013e318280e729
  5. Srinath AI, Walter C, Newara MC, et al. Pain management in patients with inflammatory bowel disease: insights for the clinician. Therap Adv Gastroenterol 2012;5(5):339–57. https://doi.org/10.1177/1756283x12446158
  6. Kefalakes H, Stylianides TJ, Amanakis G, et al. Exacerbation of inflammatory bowel diseases associated with the use of nonsteroidal anti-inflammatory drugs: myth or reality? Eur J Clin Pharmacol 2009;65(10):963–70. https://doi.org/10.1007/s00228-009-0719-3
  7. Lauritano EC, Gabrielli M, Scarpellini E, et al. Antibiotic therapy in small intestinal bacterial overgrowth: rifaximin versus metronidazole. Eur Rev Med Pharmacol Sci 2009;13(2):111–6. https://www.europeanreview.org/wp/wp-content/uploads/606.pdf
  8. Mikocka-Walus A, Ford AC, Drossman DA. Antidepressants in inflammatory bowel disease. Nat Rev Gastroenterol Hepatol 2020;17, 184–92. https://doi.org/10.1038/s41575-019-0259-y
  9. Sinniger V, Pellissier S, Fauvelle F, et al. A 12-month pilot study outcomes of vagus nerve stimulation in Crohn’s disease. Neurogastroenterol Motil 2020;e13911. https://doi.org/10.1111/nmo.13911
  10. Kapural L, Gupta M, Paicius R, et al. Treatment of chronic abdominal pain with 10-khz spinal cord stimulation: safety and efficacy results from a 12-month prospective, multicenter, feasibility study. Clin Transl Gastroenterol 2020;11(2):e00133. https://dx.doi.org/10.14309%2Fctg.0000000000000133
  11. Knotkova H, Cruciani RA. Non-invasive transcranial direct current stimulation for the study and treatment of neuropathic pain. Methods Mol Biol 2010;617:505–15. https://doi.org/10.1007/978-1-60327-323-7_37
  12. Volz MS, Farmer A, Siegmund B. Reduction of chronic abdominal pain in patients with inflammatory bowel disease through transcranial direct current stimulation: a randomized controlled trial. Pai. 2016;157(2):429–37. https://doi.org/10.1097/j.pain.0000000000000386

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