ArticleProceedings of the National Academy of Sciences of the United States of America2012
Reactive oxygen species are second messengers of neurokinin signaling in peripheral sensory neurons.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 99 citations in OpenAlex.
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- Selenized neural stem cell-derived exosomes: A neotype therapeutic agent for traumatic injuries of the central nervous system.Cell reports. Medicine · 2025Article
- Protective effects of Notoginsenoside R2 on reducing lipid accumulation and mitochondrial dysfunction in diabetic nephropathy through regulation of c-Src.Chinese medicine · 2025Article
- Article
- Neuronal regulation of bone and tendon injury repair: a focused review.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Review
- Calcium-sensing receptor regulates Kv7 channels via GBritish journal of pharmacology · 2024Article
- The effect of SP/NK1R on expression and activity of glutaredoxin and thioredoxin proteins in prostate cancer cells.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Mitochondrial oxidative damage reprograms lipid metabolism of renal tubular epithelial cells in the diabetic kidney.Cellular and molecular life sciences : CMLS · 2024Article
- Therapeutic role of voltage-gated potassium channels in age-related neurodegenerative diseases.Frontiers in cellular neuroscience · 2024Review
- Development of an activatable far-red fluorescent probe for rapid visualization of hypochlorous acid in live cells and mice with neuroinflammation.Frontiers in chemistry · 2024Article
- Photobiomodulation and vitamin B treatment alleviate both thermal and mechanical orofacial pain in rats.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2023Article
- Over-expression of miR-3584-5p Represses Nav1.8 Channel Aggravating Neuropathic Pain caused by Chronic Constriction Injury.Molecular neurobiology · 2023Article
- Carbohydrate-Based NK1R Antagonists with Broad-Spectrum Anticancer Activity.Journal of medicinal chemistry · 2021Article
- Pathogenic role of the SP/ NK1R system in GBM cells through inhibiting the thioredoxin system.Iranian journal of basic medical sciences · 2021Article
- Neurogenic substance P-influences on action potential production in afferent neurons of the kidney?Pflugers Archiv : European journal of physiology · 2021Article
- Mitochondria Homeostasis and Oxidant/Antioxidant Balance in Skeletal Muscle-Do Myokines Play a Role?Antioxidants (Basel, Switzerland) · 2021Review
- Delineating an extracellular redox-sensitive module in T-type CaThe Journal of biological chemistry · 2020Article
- Neurokinin-1 receptor is an effective target for treating leukemia by inducing oxidative stress through mitochondrial calcium overload.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- A mutually induced conformational fit underlies CaThe Journal of biological chemistry · 2019Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
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 G(i/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 Ca(2+) 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 Ca(2+) 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.
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