J Neurogastroenterol Motil.  2015 Oct;21(4):560-570. 10.5056/jnm15048.

Molecular and Cellular Characteristics of the Colonic Pseudo-obstruction in Patients With Intractable Constipation

• Do YS
• Myung SJ
• Kwak SY
• Cho S
• Lee E
• Song MJ
• Yu CS
• Yoon YS
• Lee HK

• KMID: 2381305
• DOI: http://doi.org/10.5056/jnm15048

Abstract

BACKGROUND/AIMS
Chronic intestinal pseudo-obstruction (CIPO) is a disorder characterized by recurrent symptoms suggestive of obstruction such as abdominal pain, proximal distension with extremely suppressed motility in the absence of lumen-occluding lesion, whose etiology/pathophysiology is poorly understood. In this study we investigated a functionally obstructive lesion that could underlie symptoms of CIPO.
METHODS
We studied colons surgically removed from 13 patients exhibiting clinical/pathological features of pseudo-obstruction but were unresponsive to standard medical treatments. The colons were characterized morphologically, functionally and molecularly, which were compared between regions and to 28 region-matched controls obtained from colon cancer patients.
RESULTS
The colons with pseudo-obstruction exhibited persistent luminal distension proximally, where the smooth muscle was hypertrophied with changes in the cell phenotypes. Distinct luminal narrowing was observed near the distal end of the dilated region, close to the splenic flexure, previously referred to as the "transition zone (TZ)" between the dilated and non-dilated loops. Circular muscles from the TZ responded less to depolarization and cholinergic stimulation, which was associated with down-regulation of L-type calcium channel expression. Smooth muscle contractile protein was also downregulated. Myenteric ganglia and neuronal nitric oxide synthase (nNOS) positive cells were deficient, more severely in the TZ region. Interstitial cells of Cajal was relatively less affected.
CONCLUSIONS
The TZ may be the principal site of functional obstruction, leading to proximal distension and smooth muscle hypertrophy, in which partial nNOS depletion could play a key role. The neuromuscular abnormalities probably synergistically contributed to the extremely suppressed motility observed in the colonic pseudo-obstruction.

Keyword

Colon; Hypoganglionosis; Intestinal Pseudo-obstruction; Nitric oxide; Smooth muscle

MeSH Terms

Abdominal Pain
Calcium Channels, L-Type
Colon*
Colon, Transverse
Colonic Neoplasms
Colonic Pseudo-Obstruction*
Constipation*
Down-Regulation
Ganglia
Humans
Hypertrophy
Interstitial Cells of Cajal
Intestinal Pseudo-Obstruction
Muscle, Smooth
Muscles
Nitric Oxide
Nitric Oxide Synthase Type I
Phenobarbital
Phenotype
Calcium Channels, L-Type
Nitric Oxide
Nitric Oxide Synthase Type I
Phenobarbital