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​My Health

Gut Microbiota Can Regulate Visceral Pain

6/26/2017

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Adam Hassan, BSc Microbiology and Immunology
Contributor​


Pain is medically defined as “an unpleasant sensation that can range from mild, localized discomfort to agony.” (1) Now, there are a few types of pain and the classification of it is a whole study in itself. One that we will particularly focus on is called visceral pain. It is one of the most common types associated with disease and also one of the most frequent reasons why patients go see a doctor. This type refers to a pain that results from the activation of nociceptors, sensory neurons that send pain signals to the brain, of the thoracic, pelvic, or abdominal viscera (organs).

True visceral pain is characterized as a vague, diffuse, and poorly defined sensation. Patients tend to report a vague sensation of malaise. (2) It is important to go and visit a medical specialist if this type of sensation continues over a lengthy period of time. Treatment of the pain in many circumstances should be deferred until the origin of the symptoms has been identified. Masking pain may confound the diagnostic process and delay the recognition of life-threatening conditions. (3)

An emerging study these days is the link between our gut bacteria and visceral pain. Studies have shown that the absence of gastrointestinal (GI) bacteria, such as which occurs in germ free (GF) mice, is associated with a reduced perception of pain following different inflammatory stimuli. (4) Thus, these mice, which are devoid of bacteria colonizing their gut, do not perceive pain under the same conditions that ‘normal’ mice would. Furthermore, modulation of the intestinal microbiome by administration of various probiotics also has been shown to alter pain responses. (5)

Now, this doesn’t only work on a physiological level, but a genetic one as well. The microbiome (the ensemble of genes of the microbiota) can influence both peripheral and central neurological activity by a variety of mechanisms. The early neonatal period is a critical time for the development of the nervous system, including the enteric (gut) nervous system. Recent studies comparing the development of the enteric nervous system in GF mice and specific pathogen-free mice suggest that the intestinal microbiota plays an important role in shaping this process. (6) It is thanks to our nervous system that we are able to perceive different stimuli such as temperature, pressure, and pain. Therefore, our gut microbiota is essential in shaping the framework through which we recognize when we are injured or hurt.

​A lot of these studies have been performed within animal models which have been useful to demonstrate potential mechanisms by which the microbiome can modulate visceral pain responses. In GF mice, contact with commensal (co-existing without causing harm) microbiota is necessary for mice to develop pain sensitivity. (7) The mechanisms by which the gut microbiota is capable of inducing or reducing visceral hypersensitivity are slowly being uncovered. It is clear that stress either chronic or in early life is a key factor in potentiating visceral pain responses and its associated comorbidities.

Earlier, we mentioned that visceral pain is one of the most common types associated with disease. Here is an example of how this works. Visceral pain is a known complication in patients suffering from irritable bowel syndrome (IBS). These patients tend to experience a lot of hypersensitivity. IBS is characterized by chronic abdominal pain and discomfort. Growing evidences suggest that IBS patients have a dysbiotic (abnormal) intestinal microbiota. Approximately 8% of children experience recurrent functional abdominal pain and about 61% of these children continue to report abdominal pain or IBS. (8) IBS patients show an altered profile of gut microbiota composition. Earlier studies found that the intestinal microbiota in IBS patients differs from that in healthy individuals, with a consistent decrease in the Bifidobacterium spp. population and an increase in the Enterobacter population. Other studies in patients with IBS have shown alterations in the microbiota, such as an increased ratio of Firmicutes to Bacteroidetes and a reduction in Lactobacillus species. Symptoms of IBS may be linked to those alterations. (7) Therefore, the types of bacteria present within our gut are of great importance in determining whether or not one is more susceptible to disease.

In summary, the microbiome, gut and brain have a complex set of interactions that modulate responses to visceral pain. Various psychological, infectious and other stressors can disrupt this harmonious relationship and alter both the microbiome and visceral pain responses. If you are ever suffering from an unknown sense of malaise, it is important to go seek the advice of a health professional. It may be more serious and more complex than you know!
 
References
1. Medicine Net. "Medical Definition of Pain." MedicineNet. MedicineNet, 2016.
2. Procacci P, et al. In: Cervero F, Morrison JFB (Eds). Visceral Sensation, Progress in Brain Research, Vol. 67. Amsterdam: Elsevier, 1986, pp 21–28.
3. Giamberardino MA. In: Devor M, et al. (Eds). Proceedings of the 9th World Congress on Pain, Progress in Pain Research and Management, Vol. 16. Seattle: IASP Press, 2000, pp 523–550.
4. Amaral, F. A., D. Sachs, V. V. Costa, C. T. Fagundes, D. Cisalpino, T. M. Cunha, S. H. Ferreira, F. Q. Cunha, T. A. Silva, J. R. Nicoli, L. Q. Vieira, D. G. Souza, and M. M. Teixeira. "Commensal Microbiota Is Fundamental for the Development of Inflammatory Pain." Proceedings of the National Academy of Sciences of the United States of America. U.S. National Library of Medicine, 12 Feb. 2008. Web.
5. Verdú, E. F., P. Bercik, M. Verma-Gandhu, X. X. Huang, P. Blennerhassett, W. Jackson, Y. Mao, L. Wang, F. Rochat, and S. M. Collins. "Specific Probiotic Therapy Attenuates Antibiotic Induced Visceral Hypersensitivity in Mice." Gut. U.S. National Library of Medicine, Feb. 2006. Web.
6. Borre, Y. E., G. W. O'Keeffe, G. Clarke, C. Stanton, T. G. Dinan, and J. F. Cryan. "Microbiota and Neurodevelopmental Windows: Implications for Brain Disorders." Trends in Molecular Medicine. U.S. National Library of Medicine, Sept. 2014. Web.
7. Chichlowski, Maciej, and Colin Rudolph. "Visceral Pain and Gastrointestinal Microbiome." Journal of Neurogastroenterology and Motility. Korean Society of Neurogastroenterology and Motility, Apr. 2015. Web.
8. O'Mahony, S. M., J. R. Marchesi, P. Scully, C. Codling, A. M. Ceolho, E. M. Quigley, J. F. Cryan, and T. G. Dinan. "Early Life Stress Alters Behavior, Immunity, and Microbiota in Rats: Implications for Irritable Bowel Syndrome and Psychiatric Illnesses." Biological Psychiatry. U.S. National Library of Medicine, 01 Feb. 2009. Web.
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