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...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-04-01
|
| Series: | Life |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-1729/15/4/640 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850144746104684544 |
|---|---|
| author | Alvaro Yogi Umberto Banderali Maria J. Moreno Marzia Martina |
| author_facet | Alvaro Yogi Umberto Banderali Maria J. Moreno Marzia Martina |
| author_sort | Alvaro Yogi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ee6b76a452e94a83bfa59a569199b5da |
| institution | OA Journals |
| issn | 2075-1729 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj-art-ee6b76a452e94a83bfa59a569199b5da2025-08-20T02:28:15ZengMDPI AGLife2075-17292025-04-0115464010.3390/life15040640Preclinical Animal Models to Investigate the Role of Na<sub>v</sub>1.7 Ion Channels in PainAlvaro Yogi0Umberto Banderali1Maria J. Moreno2Marzia Martina3Human Health Therapeutics Research Centre, National Research Council Canada, Ottawa, ON K1A 0R6, CanadaHuman Health Therapeutics Research Centre, National Research Council Canada, Ottawa, ON K1A 0R6, CanadaHuman Health Therapeutics Research Centre, National Research Council Canada, Ottawa, ON K1A 0R6, CanadaHuman Health Therapeutics Research Centre, National Research Council Canada, Ottawa, ON K1A 0R6, CanadaChronic 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.https://www.mdpi.com/2075-1729/15/4/640Na<sub>v</sub>1.7painneuropathicinflammatorypre-clinical model |
| spellingShingle | Alvaro Yogi Umberto Banderali Maria J. Moreno Marzia Martina Preclinical Animal Models to Investigate the Role of Na<sub>v</sub>1.7 Ion Channels in Pain Life Na<sub>v</sub>1.7 pain neuropathic inflammatory pre-clinical model |
| title | Preclinical Animal Models to Investigate the Role of Na<sub>v</sub>1.7 Ion Channels in Pain |
| title_full | Preclinical Animal Models to Investigate the Role of Na<sub>v</sub>1.7 Ion Channels in Pain |
| title_fullStr | Preclinical Animal Models to Investigate the Role of Na<sub>v</sub>1.7 Ion Channels in Pain |
| title_full_unstemmed | Preclinical Animal Models to Investigate the Role of Na<sub>v</sub>1.7 Ion Channels in Pain |
| title_short | Preclinical Animal Models to Investigate the Role of Na<sub>v</sub>1.7 Ion Channels in Pain |
| title_sort | preclinical animal models to investigate the role of na sub v sub 1 7 ion channels in pain |
| topic | Na<sub>v</sub>1.7 pain neuropathic inflammatory pre-clinical model |
| url | https://www.mdpi.com/2075-1729/15/4/640 |
| work_keys_str_mv | AT alvaroyogi preclinicalanimalmodelstoinvestigatetheroleofnasubvsub17ionchannelsinpain AT umbertobanderali preclinicalanimalmodelstoinvestigatetheroleofnasubvsub17ionchannelsinpain AT mariajmoreno preclinicalanimalmodelstoinvestigatetheroleofnasubvsub17ionchannelsinpain AT marziamartina preclinicalanimalmodelstoinvestigatetheroleofnasubvsub17ionchannelsinpain |