Review article
Treatment of spastic esophageal motility disorders

https://doi.org/10.1016/S0889-8553(03)00129-8Get rights and content

Section snippets

Problems with therapeutic trials in patients with spastic motility

Despite the frequently noted prevalence of these disorders, their cause, pathophysiology, and importance remains to be determined [3]. The structural basis of the abnormal esophageal motility patterns has been difficult to study because most of these patients do not require surgery or rarely, if ever, come to autopsy. It is unclear whether the manometric abnormalities in patients with NCCP have physiologic consequences. During manometry, patients noted to have simultaneous contractions

Pharmacologic treatment

Traditionally, pharmacologic options for painful motility disorders have been directed at reducing or improving the abnormal esophageal pressures or uncoordinated motility. The pharmacologic agents used for this purpose include nitrates, calcium antagonists (such as nifedipine or diltiazem), and anticholinergic compounds [8]. Long-term outcome studies are unavailable, and most of the basis for therapy in this area remains anecdotal [9]. In addition to the agents mentioned previously, we

Tricyclic antidepressants

Psychiatric illness has been reported in as many as 84% of cases of patients with chest pain and esophageal dysmotility [55]. Investigators have found a higher prevalence of psychiatric diagnoses among patients with NEMD when compared with patients having achalasia or normal manometry. The most common psychiatric diagnoses identified among these patients include anxiety disorders, depression, somatization, and perceived vulnerability to serious heart disease and panic disorders [55], [56], [57]

Selective serotonin reuptake inhibitors

The results of the previously described trials with imipramine and trazodone raise the possibility that other psychotropic agents may be effective for the treatment of patients suffering from recurrent chest pain. This is important because the traditionally available agents imipramine and trazodone can produce undesirable effects, such as anticholinergic reactions, antiarrhythmic activity, and sedating effects, which limit their use. Furthermore, trazodone can induce priapism. Imipramine has

Enhanced visceral pain perception

The studies described above have shown a discordant outcome between the changes in esophageal motility and therapeutic outcome and thus have raised the possibility that mechanisms other than disturbed motility may contribute to the patients' symptoms. Several investigators have observed an increased pain perception (nociception or visceral hyperalgesia) in patients with chest pain after a variety of stimuli [71], [72], [73], [74], [75]. Schapiro et al [71] reproduced chest pain by intra-atrial

Pharmacologic treatment for visceral perception

The finding of visceral hyperalgesia in patients with NCCP has shifted therapeutic efforts to seek agents that can blunt visceral sensation. Beause visceral hyperalgesia is an abnormality shared by patients with other functional GI disorders, it is possible that drugs capable of producing a beneficial effect for patients with IBS might offer the same salutatory effects for those with NCCP.

Summary

Treatment of spastic motility disorders continues to be challenging. Therapeutic options remain limited due in part to our lack of understanding of the pathophysiology and significance of these disorders. Furthermore, most of therapeutic trials to date are hampered by the poorly designed nature of the study, including the small size of the trials and the lack of placebo arm. Most of the available information suggests that there seems to be an important dissociation between symptoms (chest

First page preview

First page preview
Click to open first page preview

References (105)

  • M Storr et al.

    Treatment of symptomatic diffuse esophageal spasm by endoscopic injections of botulinum toxin: a prospective study with long-term follow-up

    Gastrointest Endosc

    (2001)
  • J.E Richter et al.

    Verapamil: a potent inhibitor of esophageal contractions in the baboon

    Gastroenterology

    (1982)
  • J.E Richter et al.

    Abnormal sensory perception in patients with esophageal chest pain

    Gastroenterology

    (1986)
  • B Bromm et al.

    Imipramine reduces experimental pain

    Pain

    (1986)
  • I Varia et al.

    Randomized trial of sertraline in patients with unexplained chest pain of noncardiac origin

    Am Heart J

    (2000)
  • R.O Cannon et al.

    Abnormal cardiac sensitivity in patients with chest pain and normal coronary arteries

    J Am Coll Cardiol

    (1990)
  • A Chauhan et al.

    Abnormal cardiac pain perception in syndrome X

    J Am Coll Cardiol

    (1994)
  • H Mertz et al.

    Altered rectal perception is a biological marker of patients with irritable bowel syndrome

    Gastroenterology

    (1995)
  • J.E Kellow

    Sphincter of Oddi dysfunction type III: another manifestation of visceral hyperalgesia?

    Gastroenterology

    (1999)
  • B.T Johnston et al.

    Effects of octreotide on esophageal visceral perception and cerebral evoked potentials induced by balloon distension

    Am J Gastroenterol

    (1999)
  • M Delvaux et al.

    The kappa agonist fedotozine relieves hypersensitivity to colonic distention in patients with irritable bowel syndrome

    Gastroenterology

    (1999)
  • R Fass et al.

    The clinical and economic value of a short course of omeprazole in patients with noncardiac chest pain

    Gastroenterology

    (1998)
  • M.H Mellow

    Effect of isosorbide and hydralazine in painful primary esophageal motility disorders

    Gastroenterology

    (1982)
  • S.J Spechler et al.

    Classification of oesophageal motility abnormalities

    Gut

    (2001)
  • P.J Kahrilas

    Esophageal motility disorders: current concepts of pathogenesis and treatment

    Can J Gastroenterol

    (2000)
  • P.J Kahrilas

    Nutcracker esophagus: an idea whose time has gone?

    Am J Gastroenterol

    (1993)
  • S.R Achem et al.

    Current medical therapy for esophageal motility disorders

    Am J Med

    (1992)
  • S.R Achem et al.

    Unexplained chest pain at the turn of the century

    Am J Gastroenterol

    (1999)
  • M Storr et al.

    Esophageal pharmacology and treatment of primary motility disorders

    Dis Esophagus

    (1999)
  • R.C Orlando et al.

    Clinical and manometric effects of nitroglycerin in diffuse esophageal spasm

    N Engl J Med

    (1973)
  • H.G Preiksaitis et al.

    Nitric oxide mediates inhibitory nerve effects in human esophagus and lower esophageal sphincter

    Dig Dis Sci

    (1994)
  • N Anand et al.

    Role of nitric oxide in esophageal peristalsis

    Am J Physiol

    (1994)
  • J.W Konturek et al.

    Endogenous nitric oxide in the control of esophageal motility in humans

    J Physiol Pharmacol

    (1997)
  • R.H Boger et al.

    The clinical pharmacology of L-arginine

    Annu Rev Pharmacol Toxicol

    (2001)
  • J.W Konturek et al.

    Diffuse esophageal spasm: a malfunction that involves nitric oxide?

    Scand J Gastroenterol

    (1995)
  • Y.C Luiking et al.

    Effects of long-term oral L-arginine on esophageal motility and gallbladder dynamics in healthy humans

    Am J Physiol

    (1998)
  • M Bortolotti et al.

    Clinical and manometric effects of L-arginine in patients with chest pain and oesophageal motor disorders

    Ital J Gastroenterol Hepatol

    (1997)
  • S Moncada et al.

    The L-arginine-nitric oxide pathway

    N Engl J Med

    (1993)
  • A Lerman et al.

    Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans

    Circulation

    (1998)
  • A.J Eherer et al.

    Effect of sildenafil on oesophageal motor function in healthy subjects and patients with oesophageal motor disorders

    Gut

    (2002)
  • J.B Hollis et al.

    Effects of cholinergic stimulation on human esophageal peristalsis

    J Appl Physiol

    (1976)
  • B Greenwood

    Muscarinic receptor regulation of the esophagus and lower esophageal sphincter

    Dysphagia

    (1994)
  • T.I Bonner et al.

    Identification of a family of muscarinic acetylcholine receptor genes

    Science

    (1987)
  • J Wang et al.

    Human esophageal smooth muscle cells express muscarinic receptor subtypes M(1) through M(5)

    Am J Physiol Gastrointest Liver Physiol

    (2000)
  • W.J Dodds et al.

    Effect of atropine on esophageal motor function in humans

    Am J Physiol

    (1981)
  • B.H Jaup et al.

    Effect of pirenzepine compared with atropine and L-hyoscyamine on esophageal peristaltic activity in humans

    Scand J Gastroenterol

    (1982)
  • W.G Paterson et al.

    Effect of intraesophageal location and muscarinic blockade on balloon distension-induced chest pain

    Dig Dis Sci

    (1991)
  • J.N Blackwell et al.

    Oral pirenzepine does not affect esophageal pressures in man

    Dig Dis Sci

    (1986)
  • E Erckenbretch et al.

    The effects of pirenzipine on esophageal motility

    Scand J Gastroenterol

    (1982)
  • M Hongo et al.

    Comparison of effects of nifedipine, propantheline bromide, and the combination on esophageal motor function in normal volunteers

    Dig Dis Sci

    (1984)
  • Cited by (0)

    View full text