Background/Purpose: Increasing evidence suggests that the enteric nervous s
ystem is under the control of neurotrophins. Nerve growth factor (NGF), bra
in-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrop
hin-4/5 (NT-4/5), promote differentiation, growth, and survival of various
central and peripheral nervous system neurons. The biological effects of ne
urotrophins are mediated by the interactions with high-affinity tyrosine ki
nase receptors (TrkA, TrkB, TrkC). Recently, abnormalities of intramuscular
innervation have been reported in infantile hypertrophic pyloric stenosis
(IHPS). To further understand the reported abnormalities in pyloric innerva
tion in IHPS, the authors analyzed the expression of Trk receptors and the
neurotrophins content in IHPS.
Methods: Full-thickness muscle biopsy specimens were obtained from 8 IHPS p
atients (age range, 23 to 41 days) at pyloromyotomy and from 8 age-matched
controls without gastrointestinal disease at autopsy performed within 12 ho
urs after death. Indirect immunohistochemistry was performed using ABC (Avi
din Biotin peroxidase Complex) method with anti-Trk specific antibodies (A,
B,C). Quantitative analysis was performed using sandwich-type ELISA for NGF
, BDNF, NT-3, and NT-4/5.
Results: The intensity of staining of the myenteric plexus for TrkA, TrkB,
and TrkC was similar among IHPS and controls. There was a lack of TrkA-posi
tive nerve fibers in IHPS compared with controls. The quantity of total NGF
, NT-3, and BDNF in IHPS was significantly lower than in controls.
Conclusions: The reduced production of neurotrophins in IHPS may be respons
ible for the delay in the functional and structural maturation of pyloric i
nnervation in IHPS. The lack of TrkA-positive nerve fibers in pyloric muscl
e may explain the abnormal intramuscular innervation in IHPS. J Pediatr Sur
g 36:1280-1284. Copyright (C) 2001 by W.B. Saunders Company.