Neuroanatomy of Itch

Abstract

Peripheral tissues that can produce an itching sensation are the skin, the conjunctiva and the mucous membrane. In the skin, sensory nerves innervate the epidermis as well as the dermis and the subcutaneous fat tissue, although the autonomic nerves never innervate the epidermis. However, the sensory nerves causing the itching sensation seem to be located in a restricted part of the skin. Histamine has been known for decades to be a potent pruritogen in human beings and, for example, plays a key role in urticaria-associated pruritus.¹ The sensation induced by experimentally applied histamine is, however, not always itchy. Itch is a sensation mainly induced when histamine is applied to the skin by iontophoresis or by pricking, while it is rather painful when subcutaneously injected.² Clinically, release of histamine from mast cells in the upper dermis leads to urticaria that is characterized by wheal, flare and itching sensation. On the other hand, histamine release in the deep dermis or subcutaneous tissue results in angioedema that often associates with pain rather than with itch.³ The sensation caused by skin-burn also depends on the depth of damage. Itch frequently occurs in such damage in a limited and superficial manner or at the last recovering stage, while almost only pain occurs when there is deeper damage. According to a report published half a century ago, a single spicule taken from cowhage (macuna pruriens) pods induced itch most intensely if inserted to the depth of the basal membrane, while itch was never induced if the epidermis and upper dermis had been removed.⁴ Thus, it has been suggested that the peripheral origin of itch is limited to a superficial layer of skin, especially epidermis and upper dermis around the basal membrane.