Frontiers in Acute Pain Management: Emerging Concepts in Pain Pathways and the Role of VX-548 as a Novel NaV1.8 Inhibitor: A Narrative Review
Purpose of Review Despite ongoing research into alternative postsurgical pain treatments, opioids remain widely used analgesics regardless of associated adverse effects, including dependence and overdose, as demonstrated throughout the current opioid crisis. This is likely related to a failure in pr...
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creator | Kaye, Alan D. Everett, Erin S. Lehuquet, Arianna M. Mason, Joseph W. Maitski, Rebecca Plessala, Michael J. Barrie, Sonnah Baptiste, Carlo Jean Mychaskiw, George Ahmadzadeh, Shahab Shekoohi, Sahar Varrassi, Giustino |
description | Purpose of Review
Despite ongoing research into alternative postsurgical pain treatments, opioids remain widely used analgesics regardless of associated adverse effects, including dependence and overdose, as demonstrated throughout the current opioid crisis. This is likely related to a failure in proving the efficacy of alternative analgesics in clinical trials, despite strong evidence supporting the potential for effective analgesia through in vitro studies. While NaV1.7 and NaV1.8 channels have shown to be key components of pain perception, studies regarding pharmacological agents utilizing these channels as targets have largely failed to demonstrate the efficacy of these proposed analgesics when compared to current multimodal pain treatment regimens.
Recent Findings
However, the novel NaV1.8 channel inhibitor, VX-548 has surpassed previously studied NaV1.8 inhibitors in clinical trials and continues to hold promise of a novel efficacious analgesic to potentially be utilized in multimodal pain treatment on postsurgical patients. Additionally, NaV1.8 is encoded by the SCN10A, which has been shown to be minimally expressed in the brain, suggesting a lower likelihood of adverse effects in the CNS, including dependence and abuse.
Summary
Novel pharmacologic analgesics that are efficacious without the significant side effects associated with opioids have lacked meaningful development. However, recent clinical trials have shown promising results in the safety and efficacy of the pharmacological agent VX-548. Still, more clinical trials directly comparing the efficacy of VX-548 to standard of care post-surgical drugs, including opioids like morphine and hydromorphone are needed to demonstrate the long-term viability of the agent replacing current opioids with an unfavorable side effect profile. |
doi_str_mv | 10.1007/s11916-024-01295-7 |
format | Article |
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Despite ongoing research into alternative postsurgical pain treatments, opioids remain widely used analgesics regardless of associated adverse effects, including dependence and overdose, as demonstrated throughout the current opioid crisis. This is likely related to a failure in proving the efficacy of alternative analgesics in clinical trials, despite strong evidence supporting the potential for effective analgesia through in vitro studies. While NaV1.7 and NaV1.8 channels have shown to be key components of pain perception, studies regarding pharmacological agents utilizing these channels as targets have largely failed to demonstrate the efficacy of these proposed analgesics when compared to current multimodal pain treatment regimens.
Recent Findings
However, the novel NaV1.8 channel inhibitor, VX-548 has surpassed previously studied NaV1.8 inhibitors in clinical trials and continues to hold promise of a novel efficacious analgesic to potentially be utilized in multimodal pain treatment on postsurgical patients. Additionally, NaV1.8 is encoded by the SCN10A, which has been shown to be minimally expressed in the brain, suggesting a lower likelihood of adverse effects in the CNS, including dependence and abuse.
Summary
Novel pharmacologic analgesics that are efficacious without the significant side effects associated with opioids have lacked meaningful development. However, recent clinical trials have shown promising results in the safety and efficacy of the pharmacological agent VX-548. Still, more clinical trials directly comparing the efficacy of VX-548 to standard of care post-surgical drugs, including opioids like morphine and hydromorphone are needed to demonstrate the long-term viability of the agent replacing current opioids with an unfavorable side effect profile.</description><identifier>ISSN: 1531-3433</identifier><identifier>ISSN: 1534-3081</identifier><identifier>EISSN: 1534-3081</identifier><identifier>DOI: 10.1007/s11916-024-01295-7</identifier><identifier>PMID: 38963514</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Acute Pain - drug therapy ; Analgesics ; Analgesics - therapeutic use ; Chronic Pain Medicine (O Viswanath ; Clinical trials ; Drug overdose ; Humans ; Internal Medicine ; Medicine ; Medicine & Public Health ; Narcotics ; NAV1.8 Voltage-Gated Sodium Channel ; Pain ; Pain Management - methods ; Pain Medicine ; Pain, Postoperative - drug therapy ; Section Editor ; Sodium Channel Blockers - pharmacology ; Sodium Channel Blockers - therapeutic use ; Topical Collection on Chronic Pain Medicine ; Voltage-Gated Sodium Channel Blockers - pharmacology ; Voltage-Gated Sodium Channel Blockers - therapeutic use</subject><ispartof>Current pain and headache reports, 2024-11, Vol.28 (11), p.1135-1143</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c256t-3cb7832664a45aea833a71337993bd6d185375bde0a99a9ab6b62238dfbfa0c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11916-024-01295-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11916-024-01295-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38963514$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kaye, Alan D.</creatorcontrib><creatorcontrib>Everett, Erin S.</creatorcontrib><creatorcontrib>Lehuquet, Arianna M.</creatorcontrib><creatorcontrib>Mason, Joseph W.</creatorcontrib><creatorcontrib>Maitski, Rebecca</creatorcontrib><creatorcontrib>Plessala, Michael J.</creatorcontrib><creatorcontrib>Barrie, Sonnah</creatorcontrib><creatorcontrib>Baptiste, Carlo Jean</creatorcontrib><creatorcontrib>Mychaskiw, George</creatorcontrib><creatorcontrib>Ahmadzadeh, Shahab</creatorcontrib><creatorcontrib>Shekoohi, Sahar</creatorcontrib><creatorcontrib>Varrassi, Giustino</creatorcontrib><title>Frontiers in Acute Pain Management: Emerging Concepts in Pain Pathways and the Role of VX-548 as a Novel NaV1.8 Inhibitor: A Narrative Review</title><title>Current pain and headache reports</title><addtitle>Curr Pain Headache Rep</addtitle><addtitle>Curr Pain Headache Rep</addtitle><description>Purpose of Review
Despite ongoing research into alternative postsurgical pain treatments, opioids remain widely used analgesics regardless of associated adverse effects, including dependence and overdose, as demonstrated throughout the current opioid crisis. This is likely related to a failure in proving the efficacy of alternative analgesics in clinical trials, despite strong evidence supporting the potential for effective analgesia through in vitro studies. While NaV1.7 and NaV1.8 channels have shown to be key components of pain perception, studies regarding pharmacological agents utilizing these channels as targets have largely failed to demonstrate the efficacy of these proposed analgesics when compared to current multimodal pain treatment regimens.
Recent Findings
However, the novel NaV1.8 channel inhibitor, VX-548 has surpassed previously studied NaV1.8 inhibitors in clinical trials and continues to hold promise of a novel efficacious analgesic to potentially be utilized in multimodal pain treatment on postsurgical patients. Additionally, NaV1.8 is encoded by the SCN10A, which has been shown to be minimally expressed in the brain, suggesting a lower likelihood of adverse effects in the CNS, including dependence and abuse.
Summary
Novel pharmacologic analgesics that are efficacious without the significant side effects associated with opioids have lacked meaningful development. However, recent clinical trials have shown promising results in the safety and efficacy of the pharmacological agent VX-548. Still, more clinical trials directly comparing the efficacy of VX-548 to standard of care post-surgical drugs, including opioids like morphine and hydromorphone are needed to demonstrate the long-term viability of the agent replacing current opioids with an unfavorable side effect profile.</description><subject>Acute Pain - drug therapy</subject><subject>Analgesics</subject><subject>Analgesics - therapeutic use</subject><subject>Chronic Pain Medicine (O Viswanath</subject><subject>Clinical trials</subject><subject>Drug overdose</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Narcotics</subject><subject>NAV1.8 Voltage-Gated Sodium Channel</subject><subject>Pain</subject><subject>Pain Management - methods</subject><subject>Pain Medicine</subject><subject>Pain, Postoperative - drug therapy</subject><subject>Section Editor</subject><subject>Sodium Channel Blockers - pharmacology</subject><subject>Sodium Channel Blockers - therapeutic use</subject><subject>Topical Collection on Chronic Pain Medicine</subject><subject>Voltage-Gated Sodium Channel Blockers - pharmacology</subject><subject>Voltage-Gated Sodium Channel Blockers - therapeutic use</subject><issn>1531-3433</issn><issn>1534-3081</issn><issn>1534-3081</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc9u1DAQxi0EomXhBTggS1x6SfG_xE5vq1ULlUqpUFVxsybJZDdVYi-2s1UfgnfG7BaQOHCa0czv-2akj5C3nJ1yxvSHyHnNq4IJVTAu6rLQz8gxL6UqJDP8-b7nhVRSHpFXMd4zJpgx_CU5kqauZMnVMflxEbxLA4ZIB0eX7ZyQ3kBuP4ODNU7o0hk9nzCsB7emK-9a3KY9u6duIG0e4DFScB1NG6Rf_YjU9_TuW1EqQyFv6LXf4Uiv4Y6fGnrpNkMzJB_O6DLPQoA07LIOdwM-vCYvehgjvnmqC3J7cX67-lRcffl4uVpeFa0oq1TIttFGiqpSoEpAMFKC5lLqupZNV3XclFKXTYcM6hpqaKqmEkKarm96YK1ckJOD7Tb47zPGZKchtjiO4NDP0UqmS82UETyj7_9B7_0cXH7OSs6V0Erk6wsiDlQbfIwBe7sNwwTh0XJmf2VlD1nZnJXdZ2V1Fr17sp6bCbs_kt_hZEAegJhXbo3h7-3_2P4EnwWcvg</recordid><startdate>20241101</startdate><enddate>20241101</enddate><creator>Kaye, Alan D.</creator><creator>Everett, Erin S.</creator><creator>Lehuquet, Arianna M.</creator><creator>Mason, Joseph W.</creator><creator>Maitski, Rebecca</creator><creator>Plessala, Michael J.</creator><creator>Barrie, Sonnah</creator><creator>Baptiste, Carlo Jean</creator><creator>Mychaskiw, George</creator><creator>Ahmadzadeh, Shahab</creator><creator>Shekoohi, Sahar</creator><creator>Varrassi, Giustino</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20241101</creationdate><title>Frontiers in Acute Pain Management: Emerging Concepts in Pain Pathways and the Role of VX-548 as a Novel NaV1.8 Inhibitor: A Narrative Review</title><author>Kaye, Alan D. ; Everett, Erin S. ; Lehuquet, Arianna M. ; Mason, Joseph W. ; Maitski, Rebecca ; Plessala, Michael J. ; Barrie, Sonnah ; Baptiste, Carlo Jean ; Mychaskiw, George ; Ahmadzadeh, Shahab ; Shekoohi, Sahar ; Varrassi, Giustino</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c256t-3cb7832664a45aea833a71337993bd6d185375bde0a99a9ab6b62238dfbfa0c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Acute Pain - drug therapy</topic><topic>Analgesics</topic><topic>Analgesics - therapeutic use</topic><topic>Chronic Pain Medicine (O Viswanath</topic><topic>Clinical trials</topic><topic>Drug overdose</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Narcotics</topic><topic>NAV1.8 Voltage-Gated Sodium Channel</topic><topic>Pain</topic><topic>Pain Management - methods</topic><topic>Pain Medicine</topic><topic>Pain, Postoperative - drug therapy</topic><topic>Section Editor</topic><topic>Sodium Channel Blockers - pharmacology</topic><topic>Sodium Channel Blockers - therapeutic use</topic><topic>Topical Collection on Chronic Pain Medicine</topic><topic>Voltage-Gated Sodium Channel Blockers - pharmacology</topic><topic>Voltage-Gated Sodium Channel Blockers - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kaye, Alan D.</creatorcontrib><creatorcontrib>Everett, Erin S.</creatorcontrib><creatorcontrib>Lehuquet, Arianna M.</creatorcontrib><creatorcontrib>Mason, Joseph W.</creatorcontrib><creatorcontrib>Maitski, Rebecca</creatorcontrib><creatorcontrib>Plessala, Michael J.</creatorcontrib><creatorcontrib>Barrie, Sonnah</creatorcontrib><creatorcontrib>Baptiste, Carlo Jean</creatorcontrib><creatorcontrib>Mychaskiw, George</creatorcontrib><creatorcontrib>Ahmadzadeh, Shahab</creatorcontrib><creatorcontrib>Shekoohi, Sahar</creatorcontrib><creatorcontrib>Varrassi, Giustino</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Current pain and headache reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kaye, Alan D.</au><au>Everett, Erin S.</au><au>Lehuquet, Arianna M.</au><au>Mason, Joseph W.</au><au>Maitski, Rebecca</au><au>Plessala, Michael J.</au><au>Barrie, Sonnah</au><au>Baptiste, Carlo Jean</au><au>Mychaskiw, George</au><au>Ahmadzadeh, Shahab</au><au>Shekoohi, Sahar</au><au>Varrassi, Giustino</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Frontiers in Acute Pain Management: Emerging Concepts in Pain Pathways and the Role of VX-548 as a Novel NaV1.8 Inhibitor: A Narrative Review</atitle><jtitle>Current pain and headache reports</jtitle><stitle>Curr Pain Headache Rep</stitle><addtitle>Curr Pain Headache Rep</addtitle><date>2024-11-01</date><risdate>2024</risdate><volume>28</volume><issue>11</issue><spage>1135</spage><epage>1143</epage><pages>1135-1143</pages><issn>1531-3433</issn><issn>1534-3081</issn><eissn>1534-3081</eissn><abstract>Purpose of Review
Despite ongoing research into alternative postsurgical pain treatments, opioids remain widely used analgesics regardless of associated adverse effects, including dependence and overdose, as demonstrated throughout the current opioid crisis. This is likely related to a failure in proving the efficacy of alternative analgesics in clinical trials, despite strong evidence supporting the potential for effective analgesia through in vitro studies. While NaV1.7 and NaV1.8 channels have shown to be key components of pain perception, studies regarding pharmacological agents utilizing these channels as targets have largely failed to demonstrate the efficacy of these proposed analgesics when compared to current multimodal pain treatment regimens.
Recent Findings
However, the novel NaV1.8 channel inhibitor, VX-548 has surpassed previously studied NaV1.8 inhibitors in clinical trials and continues to hold promise of a novel efficacious analgesic to potentially be utilized in multimodal pain treatment on postsurgical patients. Additionally, NaV1.8 is encoded by the SCN10A, which has been shown to be minimally expressed in the brain, suggesting a lower likelihood of adverse effects in the CNS, including dependence and abuse.
Summary
Novel pharmacologic analgesics that are efficacious without the significant side effects associated with opioids have lacked meaningful development. However, recent clinical trials have shown promising results in the safety and efficacy of the pharmacological agent VX-548. Still, more clinical trials directly comparing the efficacy of VX-548 to standard of care post-surgical drugs, including opioids like morphine and hydromorphone are needed to demonstrate the long-term viability of the agent replacing current opioids with an unfavorable side effect profile.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>38963514</pmid><doi>10.1007/s11916-024-01295-7</doi><tpages>9</tpages></addata></record> |
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subjects | Acute Pain - drug therapy Analgesics Analgesics - therapeutic use Chronic Pain Medicine (O Viswanath Clinical trials Drug overdose Humans Internal Medicine Medicine Medicine & Public Health Narcotics NAV1.8 Voltage-Gated Sodium Channel Pain Pain Management - methods Pain Medicine Pain, Postoperative - drug therapy Section Editor Sodium Channel Blockers - pharmacology Sodium Channel Blockers - therapeutic use Topical Collection on Chronic Pain Medicine Voltage-Gated Sodium Channel Blockers - pharmacology Voltage-Gated Sodium Channel Blockers - therapeutic use |
title | Frontiers in Acute Pain Management: Emerging Concepts in Pain Pathways and the Role of VX-548 as a Novel NaV1.8 Inhibitor: A Narrative Review |
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