Skip to main content
placeholder image

Reactive oxygen species are second messengers of neurokinin signaling in peripheral sensory neurons

Journal Article


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.

Authors


  •   Linley, John (external author)
  •   Ooi, Lezanne
  •   Pettinger, Louisa (external author)
  •   Kirton, Hannah (external author)
  •   Boyle, John P. (external author)
  •   Peers, Chris (external author)
  •   Gamper, Nikita (external author)

Publication Date


  • 2012

Citation


  • Linley, J. E., Ooi, L., Pettinger, L., Kirton, H., Boyle, J. P., Peers, C. & Gamper, N. (2012). Reactive oxygen species are second messengers of neurokinin signaling in peripheral sensory neurons. Proceedings of the National Academy of Sciences of USA, 109 E1578-E1586.

Scopus Eid


  • 2-s2.0-84862187583

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/4646

Has Global Citation Frequency


Start Page


  • E1578

End Page


  • E1586

Volume


  • 109

Place Of Publication


  • United States

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.

Authors


  •   Linley, John (external author)
  •   Ooi, Lezanne
  •   Pettinger, Louisa (external author)
  •   Kirton, Hannah (external author)
  •   Boyle, John P. (external author)
  •   Peers, Chris (external author)
  •   Gamper, Nikita (external author)

Publication Date


  • 2012

Citation


  • Linley, J. E., Ooi, L., Pettinger, L., Kirton, H., Boyle, J. P., Peers, C. & Gamper, N. (2012). Reactive oxygen species are second messengers of neurokinin signaling in peripheral sensory neurons. Proceedings of the National Academy of Sciences of USA, 109 E1578-E1586.

Scopus Eid


  • 2-s2.0-84862187583

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/4646

Has Global Citation Frequency


Start Page


  • E1578

End Page


  • E1586

Volume


  • 109

Place Of Publication


  • United States