Nocistatin excites rostral agranular insular cortex-periaqueductal gray projection neurons by enhancing transient receptor potential cation conductance via Gαq/11-PLC-protein kinase C pathway

Endogenous Neuropeptide Nocistatin Is a Direct Agonist of Acid-Sensing Ion Channels (ASIC1, ASIC2 and ASIC3)

“…This experimental fact may partly explain the bidirectional role shown for nocistatin in in vivo experiments (i.e., participation in nociceptive and anti-nociceptive processes), although the significance of ASICs regulation by nocistatin in neurons of the central and peripheral nervous systems needs to be resolved in further studies. However, it is worth noting that the presence of other potential molecular targets for nocistatin was reported [31,32]. This is usual for endogenous neuropeptides to affect several receptors/channels to produce a distinct response to various concentrations of ligands.…”

“…injection of nocistatin in doses of 0.01–1 pmol per mouse induced pronociceptive responses in an algogenic-induced nociceptive flexion test in mice [30]. Up to date at least two nocistatin binding proteins have been reported on neurons: Unidentified G-coupled receptor(s) opening of canonical transient receptor potential cation (TRPC) channels through G αq/11 -phospholipase C-protein kinase C pathway [31], and NIPSNAP1, a protein of unknown function, although it is predominantly expressed in the brain, spinal cord, liver, and kidney [32].…”

Pain Regulation by Nocistatin-Targeting Molecules

“…Although PLC activation induced both PKC activation and IP 3 -medicated Ca 2+ release, the opening of TRPC cation channels is mediated by the PLC-PKC pathway through the G q/11 -coupled receptor (Ramsey, Delling, & Clapham, 2006). NST also depolarizes the projection neurons of rostral agranular insular cortex (RAIC)-PAG (Chen et al, 2009(Chen et al, , 2010. RAIC-PAG projection neurons are an essential component of brainstem descending antinociceptive circuitry, and RAIC in the insular cortex is also involved in supraspinal antinociceptive effects produced by opioid, dopamine, and GABA.…”

“…NST suppresses inhibitory neurotransmission such as glycine in the rat spinal cord in situ (Zeilhofer et al, 2000), inhibits 5-hydroxytryptamine release in the mouse neocortex synaptosome in vitro (Fantin, Fischetti, Trapella, & Morari, 2007), and induces nociception in vivo through PTX-sensitive G i/o (Inoue et al, 2003). NST has been reported to depolarize the projection neurons of periaqueductal gray (PAG) through PTX-insensitive G q/11 (Chen, Li, Yeh, Chou, & Wang, 2009;Chen et al, 2010). Identification of the NST receptor will contribute to a better understanding of biological responses evoked by NST.…”

Repeated forced swim stress prior to complete Freund’s adjuvant injection enhances mechanical hyperalgesia and attenuates the expression of pCREB and ΔFosB and the acetylation of histone H3 in the insular cortex of rat

“…However, the mechanism underlying SIH is poorly understood. Although the IC and ACC are critical to pain modulation through control of descending pain modulatory system (Burkey et al, 1996(Burkey et al, , 1999Calejesan et al, 2000;Chen et al, 2010), no study has examined the expression of DFosB and the acetylation of histone H3 in the IC and ACC in the rats with SIH.…”