Decreased Responsiveness to Chemical Itch in Old Mice

Aging is associated with altered itch perception, potentially due to changes in neuronal function and pruriceptive signaling. The underlying mechanisms, however, remain unclear. We investigated age-related differences in itch sensitivity at behavioral, cellular, and molecular levels. Young and old mice were intradermally injected with various pruritogens, including small molecules (histamine, chloroquine, and serotonin) and peptides (BAM8-22, AY-NH₂, and SLIGRL-NH₂). Scratching behavior and mechanical itch sensitivity were assessed, and calcium imaging was used to evaluate sensory neuron responses in the dorsal root ganglia. Additionally, immunofluorescence staining was performed to analyze the expression of TRPV1 and Cav3.2. Old mice exhibited reduced scratching behavior following injections, and their neuronal responses to histamine and chloroquine were diminished. Although all treated groups showed increased mechanical alloknesis, the effect was less pronounced in old animals. The expression of TRPV1 and Cav3.2 was also reduced in dorsal root ganglia neurons of old mice. These findings suggest that aging impairs both functional responsiveness and molecular signaling in sensory neurons, contributing to reduced chemical itch sensitivity in aged individuals.