Preclinical Animal Models to Investigate the Role of Na<sub>v</sub>1.7 Ion Channels in Pain
Chronic pain is a maladaptive neurological disease that remains a major global healthcare problem. Voltage-gated sodium channels (Na<sub>v</sub>s) are major drivers of the excitability of sensory neurons, and the Na<sub>v</sub> subtype 1.7 (Na<sub>v</sub>1.7) has...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-04-01
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| Series: | Life |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-1729/15/4/640 |
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| Summary: | Chronic pain is a maladaptive neurological disease that remains a major global healthcare problem. Voltage-gated sodium channels (Na<sub>v</sub>s) are major drivers of the excitability of sensory neurons, and the Na<sub>v</sub> subtype 1.7 (Na<sub>v</sub>1.7) has been shown to be critical for the transmission of pain-related signaling. This is highlighted by demonstrations that gain-of-function mutations in the Na<sub>v</sub>1.7 gene SCN9A result in various pain pathologies, whereas loss-of-function mutations cause complete insensitivity to pain. A substantial body of evidence demonstrates that chronic neuropathy and inflammation result in an upregulation of Na<sub>v</sub>1.7, suggesting that this channel contributes to pain transmission and sensation. As such, Na<sub>v</sub>1.7 is an attractive human-validated target for the treatment of pain. Nonetheless, a lack of subtype selectivity, insufficient efficacy, and adverse reactions are some of the issues that have hindered Na<sub>v</sub>1.7-targeted drug development. This review summarizes the pain behavior profiles mediated by Na<sub>v</sub>1.7 reported in multiple preclinical models, outlining the current knowledge of the biophysical, physiological, and distribution properties required for a Na<sub>v</sub>1.7 inhibitor to produce analgesia. |
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| ISSN: | 2075-1729 |