Hirschsprung’s disease (HD) is an enteric neurocristopathy, which commonly presents with neonatal intestinal obstruction. It occurs in approximately 1 in 4,000 live births. The characteristic pathological feature of HD is absence of ganglion cells extending from the internal anal sphincter for varying lengths. The gold standard curative treatment for HD is a pull-through (PT) operation to resect the aganglionic bowel to the level of healthy ganglionic bowel, which is then anastomosed proximal to the dentate line. However, a significant proportion of patients have persisting symptoms such as constipation and enterocolitis despite correctly performed PT operations. The mechanisms underlying these persistent symptoms are poorly understood and understudied. Gastrointestinal motility is controlled by four groups of cells, the enteric nervous system (ENS), interstitial cells of Cajal (ICCs), Platelet-derived growth factor receptor alpha-positive cells (PDGFRα+ cells), and smooth muscle cells (SMCs). Together, these four networks of cells regulate secretory activities and peristalsis of the bowel. We hypothesise that the ganglionic pulled-through bowel in HD is abnormal and therefore propose to investigate the morphological and molecular characteristics of the entire resected bowel specimens from patients with HD, with particular emphasis on the expression of ion channels within the smooth muscle layer, and PDGFRα+ cells.
