041 | Age‑dependent and modality‑specific changes in the phenotypic markers Nav1.8, ASIC3, P2X3 and TRPM8 in male rat primary sensory neurons during healthy aging

Cellular and Molecular Neurobiology

Author: Emanuel David Peralta | Email: peralta.emanuel@hotmail.com

Emanuel David Peralta , Diego Nicolas Messina , Cristian Gabriel Acosta

1° Universidad Nacional de Cuyo
2° Instituto de Histología y Embiología de Mendoza

Nav1.8, ASIC3, P2X3 and TRPM8 are phenotypic markers typically associated with nociception that are involved in chronic and pathological pain. Despite this, their impact on normal somatosensory perception in aged rats remains unexplored. We hypothesized that aging changes the expression and functions of these proteins in subpopulations of primary sensory neurons in the dorsal root ganglion (DRG). To test this, we combined immunohistochemistry, quantitative image analysis, Western blotting and IB4 and trkA to examine the expression levels and localization of the four nociceptive markers in different neuronal subpopulations of the DRG and cutaneous nerve terminals at ages ranging from 3 to 24 months in healthy male Wistar rats. We then used behavioral testing and in vivo pharmacological intervention to explore (a) responses to mechanical and cold stimuli and (b) whether antagonism of these proteins affects these behaviors at different ages. Geriatric rats had significantly decreased sensitivity to mechanical and cold stimuli than younger rats. In parallel, we observed differing changes in the expression of Nav1.8, ASIC3, P2X3 and TRPM8 in the DRG at different ages. Interestingly, we found that ASIC3 and P2X3 can alter normal mechanosensation and Nav1.8 and ASIC3 contribute to cold sensitivity. This is the first report detailing the changes in the expression pattern and function of Nav1.8, ASIC3, P2X3, and TRPM8 throughout aging in healthy male Wistar rats.