Oxidant-Induced Activation of cGMP-Dependent Protein Kinase Iα Mediates Neuropathic Pain After Peripheral Nerve Injury
Autor: | Wiebke Kallenborn-Gerhardt, Katharina M.J. Syhr, Ruirui Lu, Jana E. Lorenz, Achim Schmidtko, Gerd Geisslinger, Philip Eaton |
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Přispěvatelé: | Publica |
Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Physiology
Clinical Biochemistry Pharmacology Biochemistry chemistry.chemical_compound Mice Dorsal root ganglion Peripheral Nervous System medicine Animals Molecular Biology Cyclic guanosine monophosphate General Environmental Science Cyclic GMP-Dependent Protein Kinase Type I Chemistry Chronic pain Cell Biology medicine.disease Oxidants Enzyme Activation Original Research Communications medicine.anatomical_structure Nociception Peripheral nervous system Anesthesia Neuropathic pain Peripheral nerve injury General Earth and Planetary Sciences Neuralgia cGMP-dependent protein kinase Dimerization |
Popis: | 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. Antioxid. Redox Signal. 21, 1504–1515. |
Databáze: | OpenAIRE |
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