UNDERSTANDING ASIC1 EXPRESSION IN PAIN: CONTRASTING MECHANISMS IN ACUTE AND CHRONIC MOUSE MODELS

MAYRA MICAELA MONTES; ONTES, GEORGINA ORIANA MINGOLO MALNATI; LIBIA CATALINA SALINAS CASTELLANOS; OSVALDO DANIEL UCHITEL; CARINA WEISSMANN

Buenos Aires

Congreso; VI International Congress in Translational Medicine; 2023

Pain perception is a complex phenomenon involving the intricate interplay of ion channels,from the initial detection of local stimuli to the translation of electrical impulses into painsignals within the brain. Among these channels, acid-sensing ion channels (ASICs) serve ascrucial sensors that modulate neural activity in the central nervous system and respond totissue acidosis in the peripheral system. Notably, ASIC1 channels have been linked to variouspathological conditions. ASIC1 has two splice variants, ASIC1a and ASIC1b, which, to date, havebeen extensively characterized only through in situ hybridization and RT-PCR techniques, as nocommercial antibody distinguishes between them.In this work we focused on the regulation of ASIC1 RNA levels in Fabry Disease (FD), a chroniccondition, building upon prior research that highlighted ASIC1's role in acute pain using aformalin mouse model. In particular, our investigation focuses on two critical anatomicalregions: the spinal cord (SC) and dorsal root ganglia (DRGs). In both regions, heightened ASIC1channel expression was observed: comparing formalin-paw-injected mice to PBS-injectedcounterparts and contrasting GlaKO mice with their control counterparts.However, our study, facilitated by specific material dissections and RT-PCR analysis, uncovereda striking difference between the formalin-induced acute pain model and the α-galactosidaseA (Gla) deficient Fabry Disease (FD) model. In the former, ASIC1 RNA levels remainedunaltered implying a potential inverse modulation mediated by microRNAs. In contrast, in thelatter, we observed significant changes in both ASIC1a and ASIC1b RNA levels compared totheir wild-type counterparts. These results suggest distinct mechanisms contributing to pain inacute and chronic settings, with ASIC1 channels playing a pivotal role in both scenarios.These findings underscore the potential of ASIC1 channels as promising targets for furtherinvestigation in the development of future pain therapies. By dissecting the intricateregulatory mechanisms of ASIC1 expression in acute and chronic pain models, this study shedslight on novel avenues for therapeutic exploration in the realm of pain management.