OS-11 Lightning in a Bottle: Analgesia by Voltage Gated Sodium Channel 1.8 (Nav 1.8) Blockade and More

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Description: Up until recently the only drugs available to manage acute dental l pain were acetaminophen, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids. NSAIDs cannot be taken by a variety of patients due to poor renal function, a history of GI ulcers, drug allergy or sensitivity and for the possibility of adverse drug interactions with anticoagulants and lithium. Opioids are wrought with acute side effects including dizziness, drowsiness, nausea, vomiting and constipation. Their potential to cause substance misuse, physical dependence and addiction are also well described.  On January 30, 2025 suzetrigine, a novel voltage gated sodium channel 1.8 (Nav 1.8) blocking agent was granted FDA approval for the management of moderate to severe pain.  By selectively blocking the Nav 1.8 it is hoped that side effects will be less numerous and severe compared to drugs that indiscriminately block other Nav subtypes such as anticonvulsants and local anesthetics.. Unlike opioids, suzetrigine also appears to be devoid of addiction potential. In two Phase 3 post-surgical pain trials on research patients who underwent bunionectomy or abdominoplasty, suzetrigine was significantly more effective than placebo, but its analgesic effects were only equivalent to acetaminophen 325 mg plus hydrocodone 5 mg (APAP 325 mg/HYDRO 5 mg) respectively. These results are somewhat disappointing with regards to postsurgical dental pain where 440 mg naproxen sodium or APAP 500 mg plus ibuprofen 400 mg (APAP 500 mg/IBU 400 mg) have been demonstrated to provide superior analgesic effects when compared to APAP 650 mg/HYDRO 10 mg or APAP 300 mg/HYDRO 5 mg respectively.  This presentation will discuss the genesis of dental postsurgical pain, the nomenclature and anatomical  locations  of various  Nav channel subtypes and suzetrigine's possible utility and limitations in treating orofacial pain.   Suzetrigine represents only the first step to optimize the selective blockade of Nav channels to treat various patient maladies.

Learning Objectives:  

  • Discuss the mechanism of action of suzetrigine
  • Discuss the advantages and limitations of employing suzetrigine in the treatment of acute dental pain
  • Identify which patients should not receive analgesic regimens that contain ibuprofen or naproxen sodium
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