Acute irritation reveals GABAA receptor-mediated nociception in mouse dorsal root ganglion neurons through PGE2 receptor four signaling.
Physiol Rep. 2017 Apr;5(eight):
Authors: Jang IJ, Davies AJ, Akimoto N, Again SK, Lee PR, Na HS, Furue H, Jung SJ, Kim YH, Oh SB
Gamma-aminobutyric acid (GABA) depolarizes dorsal root ganglia (DRG) major afferent neurons via activation of Cl- permeable GABAA receptors however the physiologic position of GABAA receptors within the peripheral terminals of DRG neurons stays unclear. On this examine, we investigated the position of peripheral GABAA receptors in nociception utilizing a mouse mannequin of acute irritation. In vivo, peripheral administration of the selective GABAA receptor agonist muscimol evoked spontaneous licking conduct, in addition to spinal huge dynamic vary (WDR) neuron firing, after pre-conditioning with formalin however had no impact in saline-treated mice. GABAA receptor-mediated ache conduct after acute formalin remedy was abolished by the GABAA receptor blocker picrotoxin and cyclooxygenase inhibitor indomethacin. As well as, remedy with prostaglandin E2 (PGE2) was enough to disclose muscimol-induced licking conduct. In vitro, GABA induced sub-threshold depolarization in DRG neurons via GABAA receptor activation. Each formalin and PGE2 potentiated GABA-induced Ca2+ transients and membrane depolarization in capsaicin-sensitive nociceptive DRG neurons; these results have been blocked by the prostaglandin E2 receptor four (EP4) antagonist AH23848 (10 ?mol/L). Moreover, potentiation of GABA responses by PGE2 was prevented by the selective Nav1.eight antagonist A887826 (100 nmol/L). Though the perform of the Na+-Okay+-2Cl- co-transporter NKCC1 was required to take care of the Cl- ion gradient in remoted DRG neurons, NKCC1 was not required for GABAA receptor-mediated nociceptive conduct after acute irritation. Taken collectively, these outcomes reveal that GABAA receptors could contribute to the excitation of peripheral sensory neurons in irritation via a mixed impact involving PGE2-EP4 signaling and Na+ channel sensitization.
PMID: 28438981 [PubMed – indexed for MEDLINE]