1. Silent cold-sensing neurons contribute to cold allodynia in neuropathic pain.
- Author
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MacDonald DI, Luiz AP, Iseppon F, Millet Q, Emery EC, and Wood JN
- Subjects
- Animals, Mice, Mice, Inbred C57BL, Receptors, Calcitonin Gene-Related Peptide metabolism, Shaker Superfamily of Potassium Channels metabolism, Thermosensing physiology, Cold Temperature adverse effects, Hyperalgesia metabolism, Neuralgia metabolism, Neurons metabolism, Nociceptors metabolism
- Abstract
Patients with neuropathic pain often experience innocuous cooling as excruciating pain. The cell and molecular basis of this cold allodynia is little understood. We used in vivo calcium imaging of sensory ganglia to investigate how the activity of peripheral cold-sensing neurons was altered in three mouse models of neuropathic pain: oxaliplatin-induced neuropathy, partial sciatic nerve ligation, and ciguatera poisoning. In control mice, cold-sensing neurons were few in number and small in size. In neuropathic animals with cold allodynia, a set of normally silent large diameter neurons became sensitive to cooling. Many of these silent cold-sensing neurons responded to noxious mechanical stimuli and expressed the nociceptor markers Nav1.8 and CGRPα. Ablating neurons expressing Nav1.8 resulted in diminished cold allodynia. The silent cold-sensing neurons could also be activated by cooling in control mice through blockade of Kv1 voltage-gated potassium channels. Thus, silent cold-sensing neurons are unmasked in diverse neuropathic pain states and cold allodynia results from peripheral sensitization caused by altered nociceptor excitability., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)
- Published
- 2021
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