New insights into peptidergic abnormalities in Hirschsprung's disease by wholemount immunohistochemistry.

In a pilot study previously reported, we showed that individual nerves could be traced in the different layers of the gut in Hirschsprung's disease (HD) using wholemount immunohistochemistry (WI). Little is known about the course of the important nonadrenergic, noncholinergic nerves containing neuropeptides in HD. Therefore, we studied the distribution of neuropeptides in 9 HD patients and 5 controls using WI. The new findings include the following: (1) there were two populations of substance P (SP) nerves--in aganglionic gut, SP-efferent nerves were decreased but SP-afferent fibres innervating blood vessels and mucosa remained unchanged; (2) met-enkephin was present only in efferent nerves to muscle and was decreased in aganglionic gut; and (3) peptidergic nerves have a disorganised pattern in HD affecting not only aganglionic gut but also "normal" gut at the colostomy site. These peptidergic abnormalities may play an important role in the pathophysiology of HD. In particular, the imbalance of afferent and efferent innervation, a finding not previously described in HD, warrants special attention in future studies.