Regional specificities in the distribution, chemical phenotypes, and coexistence patterns of neuropeptide containing nerve fibres in the human anal canal.

Despite the pivotal clinical significance of the human anal canal, little is known about its total and specific innervation. This study assessed the comparative distribution and histotopology of nerve fibres immunoreactive for neural markers and a variety of regulatory active neuropeptides in the human anal canal by light microscopic immunohistochemistry. Depending on the epithelial zone and region of the anal canal, the neural elements were differentially immunoreactive for the pan-neural marker protein gene product 9.5, the catecholamine marker tyrosine hydroxylase, the neuroendocrine marker chromogranin A, and various neuropeptides. Protein gene product 9.5-immunoreactive nerve fibres were ubiquitously abundant in the anal canal. In the anal transitional zone, ectopic epithelial types were supplied by the same pattern of peptidergic nerves as the respective type of epithelium in normotopic location. In the dermis of the squamous zone and in the perianal epidermis, unusual distribution patterns of nerve fibres, referred to as areas of high nerve fibre density, were encountered. Double immunohistochemistry revealed region-specific coexistence patterns of neuropeptidergic nerve fibres, and novel peptide coexistence patterns were detected in anal nerve fibres. Subsets of nerve fibres formed close spatial relationships with chromogranin A-positive neuroendocrine cells, most frequently in the anal transitional zone. Chromogranin-A positive cells were shown to be present in the epithelium of perianal eccrine sweat glands. The differential distribution, peptide phenotypes and coexistence patterns of different nerve fibre populations in the human anal canal may reflect topospecific regulatory functions of neurally released neuropeptides in health and disease.