Aging Enhances Serotonergic Signaling via 5-HT₇ Receptors Underlying Mechanical Alloknesis

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-HT₇ in dorsal root ganglion neurons and the spinal dorsal horn. Pharmacological blockade of 5-HT₇ receptors attenuated itch-related behaviors, particularly mechanical alloknesis, indicating that serotonergic remodeling contributes to age-related itch hypersensitivity. These findings identify spinal 5-HT₇ signaling as a potential therapeutic target for chronic pruritus in older individuals.