**4. Visceral Pain, Peripheral Mechanisms of Pain Regulation, and IBS**

Visceral pain is a medical term for pain originating from the internal organs within the thorax or abdomen and is divided into acute and chronic pain. Acute visceral pain, caused by typically identifiable causes, is treated with appropriate therapeutic agents, including over the counter (OTC) medications such as non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen, and is relatively easy to cure. On the other hand, chronic visceral pain can be difficult to treat even with opioids, and its unknown pathology led to the creation of the term functional gastrointestinal disorders (FGIDs), a collection of many disorders in pediatric and adult patients. FGID includes terms such as irritable bowel syndrome (IBS), infant colic and abdominal migraine, or functional dyspepsia. In the gastrointestinal tract (GI tract), nociceptor nerve endings are found throughout the layers of the GI tract. They respond to many stimuli from the tract and transfer them to their cell bodies in the dorsal horn of the spinal cord [82]. After being transferred to the contralateral side of the spinal cord, the signal is then transmitted to the limbic part of the brain via the spinothalamic tract. A response is then created, and a descending inhibitory circuitry is activated, causing a release of inhibitory neurotransmitters.

In recent years, scientists studied how the microbiome of the GI tract may influence the visceral pain response. The microbial population of a person stabilizes after the first 3 years of life and from then on is relatively stable [82]. Its greatest changes are noticed during disease states; however, while disorders affecting the GI tract are the more obvious causes, GI tract dysbiosis has been observed in many other illnesses. Non-intestinal disorders, such as obesity, allergy, asthma, or autoimmune diseases can also be a factor [82–85]. Additionally, the use of broad-spectrum antibiotic treatment changes the gut microbiota, and using such antibiotics without strong clinical purpose may become a factor in IBS. In a study by Vicentini et al., mice treated with broad-spectrum antibiotics showed effects on the structure and function of the GI tract, resulting in the loss of enteric neurons in enteric plexuses. Post-treatment supplementation of short-chain fatty acids (SCFAs), naturally produced by a healthy gut microbiome, restored neuronal loss in both submucosal and myenteric plexuses [86]. Similarly, a study by De Palma et al. focused on replicating IBS dysbiosis in rats. With fecal microbiota transplant in rats, visceral hypersensitivity increased when compared to gnotobiotic rats receiving a healthy microbiota, suggesting a link between IBS-associated hypersensitivity and the intestinal microbiota [87,88].
