Expression of ASIC1 channels throughout the pain pathway in the CNS in the formalin acute pain mouse model

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

Chicago

Congreso; Annual meeting of Neuroscience 2021; 2021

Society for Neuroscience

Hindpaw injection of formalin in rodents is used to assess acute intense, short-lasting (minutes to tens of minutes) persistent pain. 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. Different channels have been shown to be involved in these responses according to specific drugs used. 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). However, whether ASIC1 protein levels are affected remains controversial, as most work focused on mRNA levels as protein levels proved difficult to detect. We decided to analyze ASIC1a protein levels at different levels in the pain pathway centrally, in regions in which ASIC1a channels are enriched (spinal cord, SC, and the anterior cingulate cortex, ACC, of the brain). In addition, we subdivided the areas into different lumbar (L) segments (SC at L3, L4 and L5 levels) as well as ipsilateral and contralateral to the injection for ACC-to avoid the dilution of any contributing effect- in formalin and PBS (control) injected mice. Our results showed the biphasic behavior of mice to formalin. This behavior was accompanied by an increase in ASIC1 levels at the contralateral ACC compared to the ipsilateral ACC and greater than in ACC of animals injected with PBS. At the spinal cord, the effect of ASIC1 levels follows a gradient stronger at L3 levels and decreasing towards L5 in formalin-injected mice. This work highlights the important role ASIC1 channels play in pain and the potential role of pharmacological therapies aiming at this channel.