Defective cholinergic innervation in pyloric muscle of patients with hypertrophic pyloric stenosis

The etiology of hypertrophic pyloric stenosis (HPS) is not known. Many investigators have studied the myenteric plexus and muscle in HPS, but there are no reports of cholinergic nerve distribution in this condition. A histochemical technique for the detection of acetylcholinesterase (AChE) has been used to study cholinergic nerve distribution. Recently, it has been shown that the development and survival of cholinergic neurons in the peripheral and central nervous system depend on the presence of nerve growth factor (NGF) and its receptor (NGFR). We examined pyloric muscle from 18 patients with HPS and 10 controls using monoclonal antibody to NGFR and AChE histochemistry. Myenteric plexus displayed strong NGFR and AChE reactivity. Quantitative assessment of immunoreactivity in nerve fibres within pyloric muscle demonstrated selective absence of NGFR and AChE-positive nerve fibres in the circular and longitudinal muscle of HPS, whereas these fibres were in abundance in the muscle of controls. These findings suggest that NGFR is an important neurotrophic factor in the maintenance of cholinergic neuronal function and that NGFR deficiency, resulting in defective cholinergic innervation of pyloric muscle, may have an important role in the pathogenesis of HPS.