Aging Enhances Serotonergic Signaling via 5-HTReceptors Underlying Mechanical Alloknesis.

Source: PubMed, NCBI / U.S. National Library of Medicine

Chronic pruritus (or itch) is a common condition associated with aging; however, the neural mechanisms driving age-related itch hypersensitivity remain largely unknown. Here, we investigated the role of serotonergic signaling in modulating itch sensitivity during aging. Aged mice exhibited enhanced mechanical alloknesis without changes in spontaneous scratching behavior, indicating that aging selectively affects mechanically evoked itch. Consistent with this phenotype, aged mice showed elevated urinary serotonin levels and increased expression of the serotonin receptor 5-HTin dorsal root ganglion neurons and the spinal dorsal horn. Pharmacological blockade of 5-HTreceptors attenuated itch-related behaviors, particularly mechanical alloknesis, indicating that serotonergic remodeling contributes to age-related itch hypersensitivity. These findings identify spinal 5-HTsignaling as a potential therapeutic target for chronic pruritus in older individuals.