ABSTRACT: Brain-body(skin) influences are bi-directional and skin should be considered as an active neuro-immuno-endocrine interface, where effector molecules act as common words used in a dynamic dialogue between brain, immune-system and skin. It has been widely demonstrated that stimuli received in the skin can influence the immune, endocrine and nervous systems at both a local and central level. However, the brain can also modulate inflammatory conditions locally induced in the skin. It has been experimentally demonstrated that intracerebral administration of the tridecapeptide α-MSH or even its COOH-terminal tripeptide can in fact inhibit cutaneous inflammation induced by the application of topical irritants and intradermal injection of cytokines. The skin can therefore alter the pharmacology of the CNS by releasing large amounts of NPs which obviously do work locally in the skin and beyond the skin. α-MSH may represent a key molecule for understanding this aspect of cutaneous-immune-neuro-endocrine-mental biological communication, being it is also generated in the skin. This molecule may in the future be used as a potent anti-inflammatory agent in clinical dermatology, and preclinical trials are presently in progress.