Silencing a Specific Set of Neurons Prevents Itching Not Controllable by Antihistamine Treatment

Itching in response to release of histamine is modulated by a set of neurons that is functionally distinct from that modulating itching not related to histamine, and these two sets of neurons can be selectively targeted and silenced.

Histaminergic itch (modulated by histamine) develops when histamine triggers an inflammatory immune response to foreign agents, such as occurs in hay fever or following an insect bite. Nonhistaminergic itch (not modulated by histamine) is seen in chronic syndromes such as dry skin itch and allergic dermatitis.

Investigators the Hebrew University of Jerusalem (Israel) and Harvard Medical School (Boston, MA, USA) studied these two types of itching by employing a strategy of reversibly silencing specific subsets of mouse sensory axons through targeted delivery of a charged sodium-channel blocker.

They found that functional blockade of histamine itch did not affect the itch evoked by chloroquine or the peptide SLIGRL-NH2 (H-Serine-Leucine-Isoleucine-Glycine-Arginine-Leucine-NH2). This peptide induces itching by binding to proteinase-activated receptor-2 (PAR2), which is not linked to histamine. Furthermore, blocking PAR2 binding did not prevent histaminerigic itch. Silencing of itch-generating fibers did not reduce pain-associated behavior.

The investigators concluded that, "These findings support the presence of functionally distinct sets of itch-generating neurons and suggest that targeted silencing of activated sensory fibers may represent a clinically useful antipruritic therapeutic approach for histaminergic and nonhistaminergic pruritus."

The study was published in the May 19, 2013, online edition of the journal Nature Neuroscience.

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Hebrew University of Jerusalem
Harvard Medical School