Acid-Sensing Ion Channel 1a in the amygdala is involved in pain and anxiety-related behaviours associated with arthritis.
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.
Clermont Université, Université d'Auvergne, Pharmacologie fondamentale et clinique de la douleur, F-63000 Clermont-Ferrand, France.|Inserm U1107 NEURO-DOL, F-63001 Clermont-Ferrand, France.
Youssef
Y
Aissouni
Centre Jean Perrin, ERTICA EA4677 Université d'Auvergne F-63001, Clermont-Ferrand, France.
Abderrahim
A
El Guerrab
Clermont Université, Université d'Auvergne, Pharmacologie fondamentale et clinique de la douleur, F-63000 Clermont-Ferrand, France.|Inserm U1107 NEURO-DOL, F-63001 Clermont-Ferrand, France.
Al Mahdy
AM
Hamieh
Clermont Université, Université d'Auvergne, Pharmacologie fondamentale et clinique de la douleur, F-63000 Clermont-Ferrand, France.|Inserm U1107 NEURO-DOL, F-63001 Clermont-Ferrand, France.
Jérémy
J
Ferrier
Clermont Université, Université d'Auvergne, Pharmacologie fondamentale et clinique de la douleur, F-63000 Clermont-Ferrand, France.|Inserm U1107 NEURO-DOL, F-63001 Clermont-Ferrand, France.
Maryse
M
Chalus
Clermont Université, Université d'Auvergne, Pharmacologie fondamentale et clinique de la douleur, F-63000 Clermont-Ferrand, France.|Inserm U1107 NEURO-DOL, F-63001 Clermont-Ferrand, France.
Diane
D
Lemaire
Clermont Université, Université d'Auvergne, Pharmacologie fondamentale et clinique de la douleur, F-63000 Clermont-Ferrand, France.|Inserm U1107 NEURO-DOL, F-63001 Clermont-Ferrand, France.
Stéphanie
S
Grégoire
Clermont Université, Université d'Auvergne, Pharmacologie fondamentale et clinique de la douleur, F-63000 Clermont-Ferrand, France.|Inserm U1107 NEURO-DOL, F-63001 Clermont-Ferrand, France.
Monique
M
Etienne
Clermont Université, Université d'Auvergne, Pharmacologie fondamentale et clinique de la douleur, F-63000 Clermont-Ferrand, France.|Inserm U1107 NEURO-DOL, F-63001 Clermont-Ferrand, France.|CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, France.
Alain
A
Eschalier
Clermont Université, Université d'Auvergne, Pharmacologie fondamentale et clinique de la douleur, F-63000 Clermont-Ferrand, France.|Inserm U1107 NEURO-DOL, F-63001 Clermont-Ferrand, France.
Denis
D
Ardid
Université Côte d'Azur, CNRS, IPMC, Valbonne, France.|LabEx Ion Channel Science and Therapeutics, Valbonne, France.
Eric
E
Lingueglia
Clermont Université, Université d'Auvergne, Pharmacologie fondamentale et clinique de la douleur, F-63000 Clermont-Ferrand, France.|Inserm U1107 NEURO-DOL, F-63001 Clermont-Ferrand, France.
Fabien
F
Marchand
D062646:Acid Sensing Ion Channel Blockers / Q000494:pharmacology; D062565:Acid Sensing Ion Channels / Q000235:genetics* / Q000378:metabolism; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000209:etiology*; D018771:Arthralgia / Q000209:etiology*; D001168:Arthritis / Q000150:complications* / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D066272:Basolateral Nuclear Complex / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D008297:Male; D009474:Neurons / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D013111:Spider Venoms / Q000494:pharmacology
D062646:Acid Sensing Ion Channel Blockers; D062565:Acid Sensing Ion Channels; C568268:Asic1 protein, rat; C413209:PcTX1 protein, Psalmopoeus cambridgei; D010455:Peptides; D013111:Spider Venoms; D051057:Proto-Oncogene Proteins c-akt