Histological evaluation of thermosensory receptors and cutaneous neurovascular in the tail skin of BALB/c mice.

Background: Thermosensory receptors in cutaneous tissues regulate body temperature. The mouse tail contains a dense network of sensory neurons that participate in temperature detection. Histological mapping of these receptors remains limited. Aim: This study aimed to examine the histological features, neural pathways, and gene activity related to thermosensory function in the dorsal tail skin of mice. Methods: Eighteen male Bagg Albino (BALB)/c mice were used. The tail skin was exposed to cold or warm stimulation. Samples were collected from the skin, spinal cord, and hypothalamus. Hematoxylin and eosin and silver staining were performed. Immunofluorescence was used to identify TRPM8- and TRPV1-positive neurons. ChIP-qPCR was used to assess histone modifications. Gene expression for TRPM8 and TRPV1 was analyzed by RT-qPCR. High-performance liquid chromatography (HPLC) was used to measure neuropeptides. Results: Histology revealed thicker dermal layers and visible vascular and nerve changes in both cold- and heat-treated skin compared with controls. Silver staining revealed increased nerve fiber (NF) density in stimulated groups. Immunofluorescence confirmed significant TRPM8 expression after cold exposure and TRPV1 expression after heat exposure, localized along dermal NFs. RT-qPCR showed a clear, significant upregulation of TRPM8 and TRPV1 genes. ChIP-qPCR revealed significantly increased histone acetylation (H3K27ac) and decreased methylation (H3K9me3) in the hypothalamus after stimulation, indicating chromatin activation. HPLC results showed elevated levels of Substance P and β-Endorphin in stimulated tissues. Conclusion: Thermal stimulation activates both peripheral and central pathways involving thermoreceptors, neuropeptides, and gene regulation. This study also shows how simple thermal exposure can alter nerve density and neurochemical signals. Thermal stimuli activate clear histological, molecular, and epigenetic responses in BALB/c mice that link the skin and brain.