Anatomical investigation of cutaneous plantar mechanoreceptor pathways and their connections to hypothalamic structures in laboratory rats.

BACKGROUND: Cutaneous mechanoreceptors detect physical stimuli. Their pathways to the CNS are not fully mapped. Understanding these connections helps explain the sensory regulation of endocrine function. AIM: This study mapped the anatomical connections between plantar skin mechanoreceptors and hypothalamic nuclei. The structural, cellular, and neurochemical features were examined. METHODS: A total of 24 male Wistar rats were used. The plantar skin was stimulated with calibrated vibration. Tissue samples were collected from the skin, spinal cord, and hypothalamus. We used Fast Blue and BDA as tract tracers to map the neural connections. Immunofluorescence was performed to label c-Fos, corticotropin-releasing hormone (CRH), calcitonin Gene-related peptide, and substance P. Confocal microscopy was used to visualize labeled pathways. We measured ACTH and corticosterone levels using hormonal assays. ChIP-qPCR was performed to detect changes in histone modifications. The gene expression of CRH, Fos, Arginine Vasopressin (AVP), NR3C1, and brain-derived neurotrophic factor (BDNF) was measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR). High-performance liquid chromatography was used to identify neuropeptide concentrations. RESULTS: Tracer analysis revealed direct afferent projections from the plantar skin to the hypothalamic paraventricular nucleus (of the hypothalamus). Immunofluorescence analysis showed strong c-Fos and CRH expression in stimulated animals. Serum adrenocorticotropic hormone and corticosterone levels increased after stimulation. Histone acetylation (H3K27ac) was elevated in hypothalamic neurons. RT-qPCR showed increased CRH, Fos, AVP, NR3C1, and BDNF expression. High-performance liquid chromatography confirmed elevated CRH, substance P, Neuropeptide Y, and β-endorphin levels after stimulation. CONCLUSION: Plantar skin mechanoreceptors directly connect to the hypothalamic regions. Mechanical stimulation activates the neuroendocrine response. This pathway integrates cutaneous sensation and hormonal regulation.