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Cold avoidance and heat pain hypersensitivity in neuronal nucleoredoxin knockout mice
Lucie Valek1, Bao Ngoc Tran1, Irmgard Tegeder1
1Institute of Clinical Pharmacology, Goethe-University, Faculty of Medicine, Frankfurt, Germany.
Free Radical Biology & Medicine
|September 20, 2022
Summary
Nucleoredoxin (NXN) loss impairs thermal sensation in mice, causing avoidance of cold and heightened heat pain. This suggests NXN
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Nucleoredoxin (NXN) is a thioredoxin-like oxidoreductase regulating calcium calmodulin kinase Camk2a.
- Camk2a is an effector in nitric oxide-mediated synaptic potentiation and nociceptive sensitization.
Purpose of the Study:
- To investigate the role of NXN in thermal sensation and nociception in mice.
- To determine the effects of pan-neuronal and sensory neuron-specific NXN deletion on sensory perception.
Main Methods:
- Generated pan-neuronal NXN knockout mice (Nestin-NXN-/-) and sensory neuron-specific NXN knockout mice (Advillin-NXN-/-).
- Assessed thermal sensation using a thermal gradient ring.
- Evaluated nociception in neuropathic and inflammatory pain models.
- Measured calcium influx, oxygen consumption, and neurite tree density in primary sensory neurons.
Main Results:
- Nestin-NXN-/- mice avoided unpleasant cold temperatures.
- Nestin-NXN-/- and Advillin-NXN-/- mice showed heightened heat nociception in pain models.
- Abnormal thermal responses correlated with increased calcium influx, oxygen consumption, and neurite density in sensory neurons.
Conclusions:
- Loss of NXN's redox balancing functions induces maladaptive changes in sensory neurons.
- NXN deficiency manifests as polyneuropathy-like cold sensitivity and heightened heat pain perception.
- NXN plays a critical role in maintaining normal thermal sensation and nociception.
