Oxidant-induced activation of cGMP-dependent protein kinase Iα mediates neuropathic pain after peripheral nerve injury.

Abstract

AIMS:

Emerging lines of evidence indicate that oxidants such as hydrogen peroxide exert specific signaling functions during the processing of chronic pain. However, the mechanisms by which oxidants regulate pain processing in vivo remain poorly understood. Here, we investigated whether cyclic guanosine monophosphate (cGMP)-dependent protein kinase Iα (cGKIα), which can be activated by oxidants independently of cGMP, serves as a primary redox target during pain processing.

RESULTS:

After peripheral nerve injury, oxidant-induced cGKIα activation is increased in dorsal root ganglia of mice. Knock-in (KI) mice in which cGKIα cannot transduce oxidant signals demonstrated reduced neuropathic pain behaviors after peripheral nerve injury, and reduced pain behaviors after intrathecal delivery of oxidants. In contrast, acute nociceptive, inflammatory, and cGMP-induced pain behaviors were not impaired in these mice.

INNOVATION:

Studying cGKIα KI mice, we provide the first evidence that oxidants activate cGKIα in sensory neurons after peripheral nerve injury in vivo.

CONCLUSION:

Our results suggest that oxidant-induced activation of cGKIα specifically contributes to neuropathic pain processing, and that prevention of cGKIα redox activation could be a potential novel strategy to manage neuropathic pain.

• Authors: Jana E Lorenz, Wiebke Kallenborn-Gerhardt, Ruirui Lu, Katharina M J Syhr, Philip Eaton, Gerd Geisslinger, Achim Schmidtko
• Journal: Antioxidants & redox signaling (Antioxid Redox Signal) Vol. 21 Issue 10 Pg. 1504-15 (Oct 01 2014) ISSN: 1557-7716 [Electronic] United States
• PMID: 24450940 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Oxidants
• Cyclic GMP-Dependent Protein Kinase Type I

Topics

• Animals
• Cyclic GMP-Dependent Protein Kinase Type I (metabolism)
• Dimerization
• Enzyme Activation
• Mice
• Neuralgia (prevention & control)
• Oxidants (pharmacology)
• Peripheral Nervous System (injuries)