Visceral hypersensitivity is an important component of irritable bowel syndrome, and affects 30-60% of patients, mostly younger and female. The pathophysiological basis of visceral hypersensitivity has not yet been fully explained, but it is believed that various peripheral and central factors, such as psychological stress and disorders of intestinal permeability, can cause a change in the bidirectional signaling of the gut-brain axis and increased sensitization of the peripheral (enteric) and central nervous system. Antispasmodics as peripheral neuromodulators are used to reduce spasms and abdominal pain. Today, antidepressants are most often used as central neuromodulators, and atypical antipsychotics are also being investigated. With their complex action on serotonin and other neurotransmitter systems, these drugs act directly and indirectly on some pathophysiological components underlying visceral hypersensitivity, and are especially useful in patients with a history of mental disorders. In various studies, substances of natural origin such as berberine and curcumin, as well as probiotics, show efficacy in reducing visceral hypersensitivity, which requires further research. Research indicates a wide spectrum of mediators and receptors involved in the transmission, perception and modulation of pain signals originating from the gastrointestinal tract, especially at the level of gut-brain communication, which are being investigated as potential new targets for more specific drugs with neuromodulatory effects on visceral hypersensitivity.