The Therapeutic Effect of Melatonin in Pediatric Patients With Functional Dyspepsia

Recurrent abdominal pain is present in a significant proportion of the pediatric population at large. Often times, no clear organic cause for pain will be found, and these children are diagnosed with functional abdominal pain. Of the children with functional abdominal pain, many are classified as having functional dyspepsia (FD). Functional dyspepsia is defined as persistent or recurrent pain or discomfort centered in the upper abdomen (above the umbilicus) that is unrelated to a change in stool frequency or form and not exclusively relieved by defecation. There have been only a few placebo controlled trials of medications in children with abdominal pain and none in children specifically with functional dyspepsia and uninvestigated mucosal inflammation.

There is increasing evidence suggesting that melatonin plays a role in pain modulation. Melatonin is produced by the pineal gland and is recognized for its regulation of sleep and circadian functions. Less widely recognized is melatonin's production in other parts of the body; such as in the digestive system and in immune cells including mast cells. The total amount of melatonin in the digestive system exceeds that of the pineal gland and blood. Within the digestive tract, melatonin is produced in the enterochromaffin cells. It exerts both excitatory and inhibitory effects on the enteric nervous system as well as possessing anti-inflammatory and immunomodulatory properties. In a rat model of reflux esophagitis, melatonin demonstrated multiple effects on the esophageal mucosa. These included decreased lipid peroxidation (oxidative degradation of lipids in cell membranes which leads to cell damage), replenished superoxide dismutase and glutathione (improved defense of the mucosa), and decreased expression of T helper 1 cytokines (pro-inflammatory cytokines) while not altering anti inflammatory cytokines. These effects may account for the reduction in pain in adults with irritable bowel syndrome (IBS) and dyspepsia during a trial of melatonin therapy. In a study of adults with IBS in association with sleep disturbances, patients were given melatonin 3mg or placebo at bedtime for two weeks. Compared with the placebo group, the group who received melatonin had significantly lower mean abdominal pain scores while sleep parameters were not influenced. In a study of adults with functional dyspepsia, twelve weeks of melatonin (5 mg taken at bedtime) resulted in 56.6% of patients having complete resolution of symptoms and 30% having partial improvement, while only 6.7% of the patients who received placebo experienced any improvement in symptoms. Melatonin has not been previously studied in children with abdominal pain. Evaluation of its effects is warranted as melatonin would be a very safe and inexpensive alternative treatment.