Pathophysiology of Biliary-Type Abdominal Pain

Abstract

We read with great interest the Review Article by Rastogy et al. [1] dealing with acalculous biliary-type abdominal pain. With respect to it we felt obliged to provide some important additional information that will shed more light onto the mechanisms underlying the pathophysiology of biliary dyskinesia.In 1978, we demonstrated that both dihydroergotamine (DHE) and phentolamine (two α-adrenergic blocking agents) interfere with cholecystokinin (CCK)-induced gallbladder emptying [2]. In addition, these agents trigger gastric hypoactivity plus duodenal spasticity and, also, interfere with CCK-induced sigmoidal motility [3,4]. The fact that x-ray visualization of the gallbladder persisted for 24 hr after DHE injection supports the postulation that α-adrenergic blockade interferes with CCK-induced motility effects. Further research carried out at our institute demonstrated that patients showing raised levels of circulating serotonin (p-5HT) did not show enough gallbladder emptying when tested with the Boyden-meal test [5]. The fact that serotonin is able to antagonize α-adrenergic receptors is consistent with the postulation that increased postprandial release of 5-HT should be an important factor responsible for biliary dyskinesia [6]. Indeed, both noradrenaline and p-5HT rise during postprandial periods; however, the rise of the latter overwhelms that of the former in patients showing high distal colon tone (spasticity) [7,8]. Conversely, the opposite profile is registered in subjects showing low distal colon tone (diarrheic patients) [7,8]. Further research work demonstrated that the autonomic nervous system (ANS) imbalance responsible for these two faces of irritable bowel syndrome (IBS)-spastic and diarrheic-includes biliary motility disorders [9]. These authors showed that α-adrenergic blockade is responsible for a ß-adrenergic-induced relaxation of the gallbladder that could interfere with the CCK response. This postulation is reinforced by our findings showing that diarrheic IBS patients presented higher than normal circulating p-5HT values [10][11][12].Other authors demonstrated that both biliary and intestinal motility disorders should be considered as links of the chain referred to the ANS imbalance; thus, biliary dyskinesia, IBS, and other gastrointestinal motility disorders should be considered as segmental expressions of an ANS imbalance, which in turn would reflect central nervous system disorders [13][14][15][16].In addition to all the above, we would like to mention that clonidine, an α-2 agonist which reduces neural sympathetic activity, is able to suppress both distal colon motility pain and biliary colic, abruptly [10,17,18]. Conversely, dihydroergotamine, an α-2 antagonist is able to suppress distal colon hypermotility in diarrheic patients, suddenly [12].The above-summarized findings provide good examples demonstrating that the controversies concerning the pathophysiology and management of acalculous biliary-type abdominal pain presented by Rastogi et al.[1] as an insulated and specific clinical ...

Central Nervous System Plus Autonomic Nervous System Disorders Responsible for Gastrointestinal and Pancreatobiliary Diseases

“…Conversely, duodenal hormones such as secretin, pancreozymin, and cholecystokinin (CCK) enhance pancreato-biliary secretions as well as gallbladder and biliary motility. However, these hormones are coupled with the ANS mechanisms into a complex physiological interaction in such a way that any ANS disorder triggers the physiological unbalance responsible for different gastrointestinal and pancreatobiliary dysfunctions [5,6]. In addition, it has been demonstrated that CCK plays primordial physiological and pathophysiological roles in the motility of the colon [7,8]; in addition, this gastrointestinal hormone crosses the blood brain barrier, at which level it interacts with CCK receptors located at the dorsal raphe serotonergic nucleus DR-5HT and provokes satiety [9,10].…”

“…segments [5,7,8,[86][87][88][89][90]. The above phenomena are registered during the spastic colon period of the IBS.…”

Clonidine Therapy for Pancreatitis

“…The rationale for this strategy was based on the pathophysiological knowledge that the inflammatory process should interfere with adequate drainage of the pancreatic juice and would exacerbate the damage at the acinar pancreas level. The absolute success of this neuropharmacological strategy has been reported in [7,8] as well as in other communications [9][10][11]. These successful therapeutic results should be understood according to findings that demonstrated that the sympathetic innervation of the pancreas arises from the Cl(Ad) medullary nuclei, which are located at the rostroventrolateral area of this central nervous system structure [12][13][14][15][16].…”

Arginine-induced pancreatitis: involvement of the autonomic nervous system?

“…The pancreatic and biliary ducts share a common ductular drainage at the choledocus and the sphincter of Oddi (3,15,17). With respect to this, we demonstrated that both neural sympathetic activity (NE) and circulating serotonin modulate biliary motility (10,13,15). These neurotransmitters play a primordial role in the gallbladder and the sphincter of Oddi motility; thus any discussion dealing with the pancreatobiliary pathophysiology might be carried out as a whole.…”

“…We also demonstrated that not only pancreatic but biliary drainage should be taken into account to understand the pathophysiology of pancreatitis. The pancreatic and biliary ducts share a common ductular drainage at the choledocus and the sphincter of Oddi (3,15,17). With respect to this, we demonstrated that both neural sympathetic activity (NE) and circulating serotonin modulate biliary motility (10,13,15).…”