Linley 2012 Proc Natl Acad Sci U S A

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Linley JE, Ooi L, Pettinger L, Kirton H, Boyle JP, Peers C, Gampera N (2012) Reactive oxygen species are second messengers of neurokinin signaling in peripheral sensory neurons. Proc Natl Acad Sci U S A 109:1578-86

» PMID: 22586118 Open Access

Linley JE, Ooi L, Pettinger L, Kirton H, Boyle JP, Peers C, Gampera N (2012) Proc Natl Acad Sci U S A

Abstract: Substance P (SP) is a prominent neuromodulator, which is produced and released by peripheral damage-sensing (nociceptive) neurons; these neurons also express SP receptors. However, the mechanisms of peripheral SP signaling are poorly understood. We report a signaling pathway of SP in nociceptive neurons: Acting predominantly through NK1 receptors and Gi/o proteins, SP stimulates increased release of reactive oxygen species from the mitochondrial electron transport chain. Reactive oxygen species, functioning as second messengers, induce oxidative modification and augment M-type potassium channels, thereby suppressing excitability. This signaling cascade requires activation of phospholipase C but is largely uncoupled from the inositol 1,4,5-trisphosphate sensitive Ca2+ stores. In rats SP causes sensitization of TRPV1 and produces thermal hyperalgesia. However, the lack of coupling between SP signaling and inositol 1,4,5-trisphosphate sensitive Ca2+ stores, together with the augmenting effect on M channels, renders the SP pathway ineffective to excite nociceptors acutely and produce spontaneous pain. Our study describes a mechanism for neurokinin signaling in sensory neurons and provides evidence that spontaneous pain and hyperalgesia can have distinct underlying mechanisms within a single nociceptive neuron. Keywords: Dorsal root ganglia

O2k-Network Lab: UK Leeds Peers C


Labels:

Stress:Oxidative stress;RONS  Organism: Rat  Tissue;cell: Nervous system  Preparation: Intact cells 


Coupling state: OXPHOS 

HRR: Oxygraph-2k