The role of pain modulators in esophageal disorders - no pain no gain.

Pain modulators have been primarily used for the management of functional esophageal disorders. Recently, these drugs have also been used for the management of other esophageal disorders, such as non-erosive reflux disease, the hypersensitive esophagus, and heartburn that is not responsive to proton pump inhibitor treatment. Several etiologies have been identified in patients with functional esophageal disorders, and these include esophageal hypersensitivity due to peripheral and/or central sensitisation, altered central processing of peripheral stimuli, altered autonomic activity, and psychological comorbidity such as depression and anxiety. Different antidepressants have been used as pain modulators and have demonstrated a beneficial effect on patients with the aforementioned esophageal disorders. Tricyclic antidepressants are the most commonly used class of drugs in clinical practice. Other antidepressants that have been used, some with more clinical success than others, include selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and trazodone. Other medications that have been used as pain modulators in esophageal disorders include adenosine antagonists, serotonin agonists, antiepileptics, and medications that ameliorate peripheral neuropathy. The mechanism by which many of the pain modulators confer their visceral analgesic effect remains to be fully elucidated. Regardless, their role and value in treating esophageal disorders have markedly increased in the last decade.