Reactive Oxygen Species Derived from NOX1/NADPH Oxidase Enhance Inflammatory Pain
Open accessAbstract
The involvement of reactive oxygen species (ROS) in an augmented sensitivity to painful stimuli (hyperalgesia) during inflammation has been suggested, yet how and where ROS affect the pain signaling remain unknown. Here we report a novel role for the superoxide-generating NADPH oxidase in the development of hyperalgesia. In mice lacking Nox1(Nox1−/Y), a catalytic subunit of NADPH oxidase, thermal and mechanical hyperalgesia was significantly attenuated, whereas no change in nociceptive responses to heat or mechanical stimuli was observed. In dorsal root ganglia (DRG) neurons of Nox1+/Y, pretreatment with chemical mediators bradykinin, serotonin, or phorbol 12-myristate 13-acetate (PMA) augmented the capsaicin-induced calcium increase, whereas this increase was significantly attenuated in DRG neurons of Nox1−/Y. Concomitantly, PMA-induced translocation of PKCε was markedly perturbed in Nox1−/Yor Nox1+/YDRG neurons treated with ROS-scavenging agents. In cells transfected with tagged PKCε, hydrogen peroxide induced translocation and a reduction in free sulfhydryls of full-length PKCε but not of the deletion mutant lacking the C1A domain. These findings indicate that NOX1/NADPH oxidase accelerates the translocation of PKCε in DRG neurons, thereby enhancing the TRPV1 activity and the sensitivity to painful stimuli.
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Nox1 is predominantly expressed in colon epithelium but also detected in other peripheral tissues, including dorsal root ganglia and vascular cells.
“Nox1 is predominantly expressed in colon epithelium, but was also detected in other peripheral tissues, including dorsal root ganglia and in vascular cells (Suh et al., 1999;Bedard and Krause, 2007;Ibi et al., 2008).”
From Neurotoxic Activation of Microglia Is Promoted by a Nox1-Dependent NADPH Oxidase (2008) · cites this paper as Ibi et al., 2008
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Cites
Wu, D. C., Jackson-Lewis, V., Vila, M., Tieu, K., Teismann, P., Vadseth, C., Choi, D.-K., Ischiropoulos, H., & Przedborski, S. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-05-01763.2002 · Cited by 1,183 · see citing works
Nox1 Is Involved in Angiotensin II–Mediated Hypertension: A Study in Nox1-Deficient Mice
Matsuno, K., Yamada, H., Iwata, K., Jin, D., Katsuyama, M., Matsuki, M., Takai, S., Yamanishi, K., Miyazaki, M., Matsubara, H., et al. (2005) · Circulation · doi:10.1161/circulationaha.105.573709 · Cited by 470 · see citing works
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Research works printed but not linked: 3
- Bhave G, Zhu W, Wang H, Brasier DJ, Oxford GS, Gereau RW 4th (2002) cAMP-dependent protein kinase regulates desensitization of the capsaicin receptor (VR1) by direct phosphor- ylation. Neuron 35:721-731.
- Schwartz ES, Lee I, Chung K, Chung JM (2008) Oxidative stress in the spinal cord is an important contributor in capsaicin-induced mechanical sec- ondary hyperalgesia in mice. Pain, in press.
- Tjolsen T, Hole K (1992) Animal models of analgesia. In: The pharmacology of pain (Dickenson A, Besson JM, eds), pp 1-20. Berlin: Springer.
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Altenhöfer, S., Radermacher, K. A., Kleikers, P. W. M., Wingler, K., & Schmidt, H. H. H. W. (2015) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5814 · Cited by 521 · see citing works
NADPH oxidase in brain injury and neurodegenerative disorders
Ma, M. W., Wang, J., Zhang, Q., Wang, R., Dhandapani, K. M., Vadlamudi, R. K., & Brann, D. W. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0150-7 · Cited by 432 · see citing works
Neurotoxic Activation of Microglia Is Promoted by a Nox1-Dependent NADPH Oxidase
Chéret, C., Gervais, A., Lelli, A., Colin, C., Amar, L., Ravassard, P., Mallet, J., Cumano, A., Krause, K.-H., & Mallat, M. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3568-08.2008 · Cited by 225 · see citing works
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Nitroxidative signaling mechanisms in pathological pain
Grace, P. M., Gaudet, A. D., Staikopoulos, V., Maier, S. F., Hutchinson, M. R., Salvemini, D., & Watkins, L. R. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2016.10.003 · Cited by 128 · see citing works
Which NADPH Oxidase Isoform Is Relevant for Ischemic Stroke? The Case for Nox 2
Kahles, T., & Brandes, R. P. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4721 · Cited by 125 · see citing works
NADPH oxidase Nox1 contributes to ischemic injury in experimental stroke in mice
Kahles, T., Kohnen, A., Heumueller, S., Rappert, A., Bechmann, I., Liebner, S., Wittko, I. M., Neumann-Haefelin, T., Steinmetz, H., Schroeder, K., et al. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.05.023 · Cited by 91 · see citing works
- Authors
- Ibi, M., Matsuno, K., Shiba, D., Katsuyama, M., Iwata, K., Kakehi, T., Nakagawa, T., Sango, K., Shirai, Y., Yokoyama, T., Kaneko, S., Saito, N., & Yabe-Nishimura, C.
- Affiliations
- Kyoto Prefectural University of Medicine (JP)
- Kyoto University (JP)
- Biosignal Research Center, Kobe University (JP)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-09-17
- Volume
- 28
- Issue
- 38
- Pages
- 9486-9494
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6671127
- OpenAlex
- W2007720003
- Cited by
- 156
- References
- 2
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 8 · 2023: 7 · 2022: 5 · 2021: 18 · 2020: 10 · 2019: 7 · 2018: 5 · 2017: 12 · 2016: 8 · 2015: 10 · 2014: 11 · 2013: 10 · 2012: 10
- FWCI
- 6.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (17790172)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- reactive oxygen species, NOX1, NADPH oxidase, inflammatory pain, hyperalgesia, dorsal root ganglion neurons, TRPV1, superoxide, hydrogen peroxide, capsaicin, sulfhydryl groups, bradykinin, serotonin, phorbol myristate acetate
- MeSH terms
- NADPH Oxidase 1, Animals, Cells, Cultured, Ganglia, Spinal, Hyperalgesia, Inflammation, NADH, NADPH Oxidoreductases, Neurons, Afferent, Nociceptors, Pain, Free Radical Scavengers, Reactive Oxygen Species, Mice, Knockout, Oxidative Stress, Inflammation Mediators, Calcium Signaling, Protein Transport, TRPV Cation Channels, Mice, Protein Kinase C-epsilon
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