NADPH oxidase-4 maintains neuropathic pain after peripheral nerve injury.

Abstract

Reactive oxygen species (ROS) contribute to sensitization of pain pathways during neuropathic pain, but little is known about the primary sources of ROS production and how ROS mediate pain sensitization. Here, we show that the NADPH oxidase isoform Nox4, a major ROS source in somatic cells, is expressed in a subset of nonpeptidergic nociceptors and myelinated dorsal root ganglia neurons. Mice lacking Nox4 demonstrated a substantially reduced late-phase neuropathic pain behavior after peripheral nerve injury. The loss of Nox4 markedly attenuated injury-induced ROS production and dysmyelination processes of peripheral nerves. Moreover, persisting neuropathic pain behavior was inhibited after tamoxifen-induced deletion of Nox4 in adult transgenic mice. Our results suggest that Nox4 essentially contributes to nociceptive processing in neuropathic pain states. Accordingly, inhibition of Nox4 may provide a novel therapeutic modality for the treatment of neuropathic pain.

• Authors: Wiebke Kallenborn-Gerhardt, Katrin Schröder, Domenico Del Turco, Ruirui Lu, Katharina Kynast, Judith Kosowski, Ellen Niederberger, Ajay M Shah, Ralf P Brandes, Gerd Geisslinger, Achim Schmidtko
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 32 Issue 30 Pg. 10136-45 (Jul 25 2012) ISSN: 1529-2401 [Electronic] United States
• PMID: 22836249 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Reactive Oxygen Species
• NADPH Oxidase 4
• NADPH Oxidases
• Nox4 protein, mouse

Topics

• Animals
• Behavior, Animal (physiology)
• Cell Count
• Ganglia, Spinal (metabolism)
• Hyperalgesia (metabolism)
• Mice
• Mice, Transgenic
• Microglia (metabolism)
• Motor Activity (physiology)
• NADPH Oxidase 4
• NADPH Oxidases (genetics, metabolism)
• Neuralgia (metabolism)
• Neurons (metabolism)
• Nociceptors (metabolism)
• Pain Measurement
• Peripheral Nerve Injuries (metabolism)
• Reactive Oxygen Species (metabolism)
• Sciatic Nerve (metabolism)