Zhao Qiaofeng, Tominaga Mitsutoshi, Toyama Sumika, Honda Kotaro, Komiya Eriko, Kamata Yayoi, Ma Hang, Takamori Kenji
Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Chiba 279-0021, Japan.
Department of Functional Morphology, Faculty of Pharmacy, Juntendo University, Chiba 279-0013, Japan.
Cells. 2025 Jun 12;14(12):889. doi: 10.3390/cells14120889.
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-NH, and SLIGRL-NH). 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.
衰老与瘙痒感知的改变有关，这可能是由于神经元功能和瘙痒信号传导的变化所致。然而，其潜在机制仍不清楚。我们在行为、细胞和分子水平上研究了与年龄相关的瘙痒敏感性差异。对年轻和年老的小鼠进行皮内注射各种致痒原，包括小分子（组胺、氯喹和血清素）和肽（BAM8-22、AY-NH和SLIGRL-NH）。评估抓挠行为和机械性瘙痒敏感性，并使用钙成像来评估背根神经节中的感觉神经元反应。此外，进行免疫荧光染色以分析TRPV1和Cav3.2的表达。年老小鼠注射后抓挠行为减少，并且它们对组胺和氯喹的神经元反应减弱。尽管所有处理组的机械性异常性疼痛均增加，但在老年动物中这种效应不太明显。年老小鼠背根神经节神经元中TRPV1和Cav3.2的表达也降低。这些发现表明，衰老损害了感觉神经元的功能反应性和分子信号传导，导致老年个体化学性瘙痒敏感性降低。
