Acid-Sensing Ion Channel 1a in the amygdala is involved in pain and anxiety-related behaviours associated with arthritis

Abstract

Chronic pain is associated with anxiety and depression episodes. The amygdala plays a key role in the relationship between emotional responses and chronic pain. Here, we investigated the role of Acid-Sensing Ion Channels 1a within the basolateral amygdala (BLA), in pain and associated anxiety in a rat model of monoarthritis (MoAr). Administration within the BLA of PcTx1 or mambalgin-1, two specific inhibitors of ASIC1a-containing channels significantly inhibited pain and anxiety-related behaviours in MoAr rats. The effect of PcTx1 was correlated with a reduction of c-Fos expression in the BLA. We examined the expression profile of ASICs and other genes in the amygdala in MoAr and sham animals, and found no variation of the expression of ASIC1a, which was confirmed at the protein level. However, an increase in the BLA of MoAr rats of both PI3Kinase mRNA and the phosphorylated form of Akt, along with Bdnf mRNA, suggest that the BDNF/PI3-kinase/Akt pathway might regulate ASIC1a in BLA neurons as demonstrated in spinal sensitisation phenomenon. We also observed changes in several kinase mRNAs expression (PICK1, Sgk1) that are potentially involved in ASIC1a regulation. These results show a crucial role of ASIC1a channels in the BLA in pain and anxiety-related behaviours during arthritis.

PI3‐kinase/Akt pathway‐regulated membrane transportation of acid‐sensing ion channel 1a/Calcium ion influx/endoplasmic reticulum stress activation on PDGF‐induced HSC Activation

“…Youssef et al. showed ASIC1a activation is associated with the PI3K/AKT pathway . Our data showed after treatment with the PI3K/AKT inhibitor LY294002, the ASIC1a expression and [Ca 2+ ] i was significantly induced in PDGF‐induced HSCs.…”

“…and Bo Duan et al. showed that PI3K/Akt signalling affects ASIC1a expression and activity via membrane transduction in neurons . This has not been reported in liver fibrosis or HSCs.…”

Fecal dysbiosis associated with colonic hypersensitivity and behavioral alterations in chronically Blastocystis-infected rats

“…Elevated-Plus-Maze (EPM) test. At D29, EPM was performed as previously described 64 . Animals were recorded for 5 min by Mediarecorder software.…”

Cryo-EM structure of the ASIC1a–mambalgin-1 complex reveals that the peptide toxin mambalgin-1 inhibits acid-sensing ion channels through an unusual allosteric effect

“…The channels are formed by combinations of ASIC subunits in homo or hetero-trimeric complexes 9 – 12 , with different subunits conferring distinct properties, exhibiting a broad range of kinetic, ion selectivity and pharmacological properties 13 – 15 . ASICs are involved in various physiological processes, including synaptic plasticity 16 , 17 , neurodegeneration 15 , and pain sensation 2 , 8 , 18 – 20 . ASICs therefore have emerged as new potential therapeutic targets in the management of psychiatric disorders, neurodegenerative diseases and pain 2 .…”