As the most primitive metazoan phylum, the Platyhelminthes occupies a unique position in nervous system evolution. Centrally, their nervous system consists of an archaic brain from which emanate one or more pairs of longitudinal nerve cords connected by commissures; peripherally, a diverse arrangement of nerve plexuses of varying complexity innervate the subsurface epithelial and muscle layers, and in the parasitic taxa they are most prominent in the musculature of the attachment organs and egg-forming apparatus. There is a range of neuronal-cell types, the majority being multi- and bipolar. The flatworm neuron is highly secretory and contains a heterogeneity of vesicular inclusions, dominated by densecored vesicles, whose contents may be released synaptically or by paracrine secretion for presumed delivery to target cells via the extracellular matrix. A wide range of sense organ types is present in flatworms, irrespective of life-styles. The repertoire of neuronal substances identified cytochemically includes all of the major candidate transmitters known in vertebrates. Two groups of native flatworm neuropeptides have been sequenced, neuropeptide F and FMRFamide-related peptides (FaRPs), and immunoreactivities for these have been localised in dense-cored neuronal vesicles in representatives of all major fiatworm groups. There is evidence of co-localisation of peptidergic and cholinergic elements; serotoninergic components generally occupy a separate set of neurons. The actions of neuronal substances in flatworms are largely undetermined, but FaRPs and 5-HT are known to be myoactive in all of the major groups, and there is immuno-cytochemical evidence that they have a role in the mechanism of egg assembly.

The neuropeptide story began in 1928 with the description by Ernst Scharrer of gland-like nerve cells in the hypothalamus of the minnow, Phoxinus laevis. Because these nerve cells were overwhelmingly specialized for secretory activity, overshadowing other neuronal properties, Scharrer termed them ‘neurosecretory neurons’. What was even more remarkable about the cells was that their products were released into the bloodstream to act as hormones, specifically neurohormones. Neurosecretory cells were identified largely on morphological grounds. That is, they could be stained with special techniques, such as chrome-haematoxylin and paraldehyde-fuchsin, although the techniques are far from specific, staining non-neurosecretory cells as well. However, the basis for the ‘special’ neurosecretory techniques is the demonstration of sulphur-containing proteins – so they are indicative of peptide-producing neurones. An alternative characteristic of neurosecretory cells is the presence of large (> 100 nm), dense-cored vesicles at the electron microscope level; these are the so-called elementary granules of neurosecretion, or ENGs. However, implicit in the concept of neurosecretion is that the prime function of the neurosecretory cell is in endocrine regulation, exerting a hormone-like control over some aspect of the organism's metabolism, by controlling endocrine glands and other effector organs. To satisfy this criterion, evidence had to be obtained of cycles of secretory activity within the cell that could be correlated with a change in the physiological condition of the organism.