The incidence of functional gallbladder disorder is unknown. The best estimate of its prevalence comes from epidemiological studies in Italy performed in the 1980s. These studies found that approximately 21 % of women and 8 % of men report biliary-like pain but have normal ultrasounds of the gallbladder.

The natural history is also poorly understood. To date, there is only one prospective trial of 21 patients with a normal-appearing gallbladder and abnormal gallbladder ejection fraction (GBEF). These patients were randomized to cholecystectomy versus no surgery and followed for up to 54 months. All ten patients in the no surgery group continued to report symptoms during the follow-up phase, whereas all patients offered surgery reported improvement in their symptoms following surgery. The published retrospective studies of patients with suspected functional gallbladder disorder are quite variable in their methods and outcome measures and report resolution of symptoms without cholecystectomy in 16–80 % of the patients. Importantly, a meta-analysis completed to determine whether patients with functional biliary pain and a low GBEF experience a better outcome after cholecystectomy in comparison to those with a normal GBEF failed to show an increased likelihood of improved symptoms after cholecystectomy in patients with suspected functional biliary pain and reduced GBEF compared to those with normal GBEF.

Normal gallbladder function is well understood and known to be quite complex. In contrast, the pathophysiology of functional gallbladder disorder is poorly understood. There are two main hypotheses to explain the cause of the pain in this disorder: (1) increased pressure from a structural or functional outflow obstruction and (2) visceral hypersensitivity. The first hypothesis postulates that functional gallbladder disorder is part of a spectrum of gallbladder disease whereby bile saturation and gallbladder dysmotility lead to crystal formation. The crystals may eventually develop into gallstones or infiltrate the gallbladder wall causing inflammation. Pain may occur from either gallstones (if present) or from inflammation of the gallbladder wall. Histologic studies have demonstrated conflicting findings and, therefore, have not universally supported this hypothesis. It remains unclear whether the histologic changes often seen in the gallbladder wall are a cause or effect of poor gallbladder motility.

Sphincter of Oddi dysfunction, another controversial disorder, has been studied as a potential cause of outflow obstruction in functional gallbladder disorder. There appears to be poor correlation, however, between GBEF and sphincter of Oddi pressures. Even though there are similarities in presentation, functional biliary sphincter of Oddi disorder and functional pancreatic sphincter of Oddi disorder seem to be distinct and separate disorders.

Finally, as in most functional gastrointestinal disorders, visceral hypersensitivity has also been implicated in the pathogenesis of functional gallbladder disorder. Visceral hypersensitivity refers to enhanced perception or responsiveness within the gut to even normal events and involves the cerebral and thalamic neural pathways communicating with the gut. This process may lead to abnormalities in the signaling pathways such as cholecystokinin which, in turn, could lead to abnormal messaging to the gallbladder and resultant pain.

Rome III criteria have been developed to assist in the diagnosis of functional gallbladder disorder (see Table 13.1). To meet these criteria, a thorough history and physical examination must be performed and structural disease or other conditions that might explain the symptoms must be excluded (see Table 13.2). Common organic diseases can be excluded by obtaining the testing listed in Table 13.3. The utility of obtaining an upper endoscopic ultrasound or more extensive imaging of the abdomen is unknown and is not currently recommended.