Esophageal and gastric nitric oxide synthesizing innervation in primary achalasia

Am J Gastroenterol. 1999 Sep;94(9):2357-62. doi: 10.1111/j.1572-0241.1999.01357.x.


Objective: We performed a qualitative and quantitative analysis of the nitrinergic neurons in the esophageal and gastric component of the lower esophageal sphincter (LES) and gastric fundus of patients with primary achalasia.

Methods: Four muscle strips were obtained from the esophagogastric junction (two from the esophageal and two from the gastric side of the LES), and two from the gastric fundus of six patients with endstage achalasia who underwent an esophagogastric myotomy plus hemifundoplication. Control specimens were obtained from eight patients who underwent surgery for cancer of the thoracic esophagus. Fixed sections were processed for NADPH-diaphorase histochemistry and the number (mean +/- SE) of nitrinergic neurons per section was visually quantified in each specimen.

Results: In the controls, nitric oxide fibers were distributed to the muscle layer and surrounding myenteric neurons of both the LES and the gastric fundus. By contrast, achalasic patients showed a marked decrease of nitric oxide nerves and labeled neurons in both esophageal and gastric components of the LES and the gastric fundus. Quantitative assessment in achalasic patients showed that the mean number of nitrinergic neurons was dramatically reduced in both the esophageal (0.2 +/- 0.1) and the gastric component (2 +/- 0.6) of the LES as compared to those in controls (15 +/- 5 and 12 +/- 4, respectively; p < 0.05); nitrinergic neurons in the gastric fundus (3 +/- 1) were significantly reduced in comparison to those of controls (10 +/- 2) (p < 0.05).

Conclusions: Our results indicate that achalasia is a motor disorder with an intrinsic inhibitory denervation of the esophageal and gastric component of the LES and of the proximal stomach, thus providing further evidence for an extraesophageal extension of the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Esophageal Achalasia / metabolism*
  • Esophagogastric Junction / innervation*
  • Esophagogastric Junction / metabolism*
  • Female
  • Gastric Fundus / innervation*
  • Gastric Fundus / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide / biosynthesis*


  • Nitric Oxide