Expression of ASIC1 channels in the Anterior Cingulate Cortex in the formalin induced acute pain mouse model

CONTRERAS, NE; WEISSMAN C; CASTELLANOS SALINAS, LC; GOBETTO MN; UCHITEL OD

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Congreso; XXXVI Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2021

Hindpaw injection of formalin in rodents is used to assess acute intense, short-lasting (minutes to tens of minutes). The response to formalin is biphasic, with an initial response in the first minutes, and a later response around 30min after the injection with an increase in licking of the paw. The initial response is thought to be contributed by inflammatory, peripheral mechanisms, while the latter is linked to central mechanisms. This model has been especially useful to analyze the effect of drugs at either phase. Using specific drugs different channels have been shown to be involved in these responses. Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in neurodegenerative diseases as well as in pain conditions. Psalmotoxin-1 (Pctx-1), a toxin that inhibits ASIC1a- constituted channels, as well as antisense ASIC1a RNA, injected in mice before the formalin test, have been previously shown to affect both phases (Mazzuca et al. 2007). Pain perception is thought to occur in the anterior cingulate cortex (ACC); studies in humans have consistently reported that painful body stimuli evoke electrical and metabolic activation in the ACC, the degrees of which are correlated with the intensity of pain (Zhao et al. 2018). Neurons in the ACC are activated in both acute and chronic pain states We have previously investigated the role of ASIC channels and LTP in the ACC and the modulation via histamine and Corticosterone. We decided to analyze ASIC1a protein levels at the anterior cingulate cortex, ACC, of the brain) in the formalin acute pain mouse model. Our results showed the biphasic behavior of mice to formalin. This behavior was accompanied by an increase in ASIC1 levels at the ACC contralateral to the injection compared to ipsilateral and greater than in ACC of animals injected with PBS. This work highlights the important role ASIC1 channels play in pain and the potential role of pharmacological therapies aiming at this channel.