Sphincter of Oddi function and dysfunction: Mechanism of SO dysfunction
The cause of SO dysfunction and the pain mechanism involved are uncertain. One potential mechanism is a neural defect leading to disturbed SO motility that may be due to a defect of the neural connections that coordinate the interaction between the duodenum, biliary tract and SO. In animals and humans, the response to CCK is altered following cholecystectomy, suggesting that the surgery may in some way affect these neural connections. The neural pathways from the gallbladder and common bile duct to the SO are thought to have an inhibitory effect on the SO. Interruption of these inhibitory neural pathways may lead to an increased tonicity of the SO with resistance to outflow in a biliary system that has lost its pressure reservoir, the gallbladder. In a small human study of patients with abdominal pain suspected to be SO dysfunction that was performed during endoscopic SO manometry, some patients after cholecystectomy did not show SO relaxation in response to artificial elevations of the common bile duct pressure by infusing saline. Normally, the SO should relax in response to elevations in the common bile duct pressure. It has also been shown that in the absence of the gallbladder, bile duct pressure is increased and the bile duct pressure increases in response to SO spasm induced by morphine, which was not seen with an intact gallbladder. There are reports of SO dysfunction following liver transplantation. After liver transplantation, the SO is essentially denervated. However, surgical interruption of neural pathways cannot be the only mechanism for SO dysfunction because patients with intact gallbladders have been shown to have manometrically proven SO dysfunction.
There is evidence that SO dysfunction may be part of a generalized motor disorder of the gastrointestinal tract. Small intestinal dysmotility has been seen in association with SO dysfunction. In one study, patients with irritable bowel syndrome and SO dysfunction demonstrated paradoxical responses to CCK more often than patients with SO dysfunction alone. A German publication found abnormal esophageal and anorectal manometry in association with SO dysfunction.
A recent study found duodenal hypersensitivity in patients with type 3 SO dysfunction, suggesting that in these patients, abdominal pain may not originate exclusively in the biliary tree. Interestingly, there was no evidence of rectal hyperalgesia, which implied a site-specific process rather than a generalized visceral hyperalgesia.
Autonomic dysregulation has also been proposed as the cause of the motility disorder. Sympathetic overactivity has been found under basal conditions and during pain episodes in patients with postcholecystectomy pain who develop pain in association with morphine administration. Furthermore, the severity of the pain in this patient group can be attenuated by clonidine, a sympathetic antagonist.
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Secondary damage to the SO may result from the passage of small stones, or following inflammation of either the biliary tract or pancreas. This may result in repair by fibrosis. Fi-
brosis of the SO has been seen in tissue acquired during surgery from patients with the diagnosis of papillitis. This may lead to a fixed structural stenosis, in keeping with the elevated basal pressure seen manometrically in patients with SO stenosis. However, some patients with an elevated basal pressure also show phasic activity, suggesting that, at least in these patients, a fixed structural lesion is unlikely.