Scholarlink

<p>Treatment of pain is a challenge for almost all clinicians, ranging from general practitioners to subspecialists such as pain medicine physicians, surgeons, neurologists and physiatrists. Over the past few years, clinical studies in people with acute postoperative pain have demonstrated that pain in humans can be reduced by inhibiting Nav1.8, a sodium channel&#xa0;that is essential for repetitive firing of peripheral pain-signalling neurons&#xa0;and has no essential function in the CNS. This discovery is an important step forward, but pain reduction in these studies was partial, not complete. Moreover, success via this approach thus far has been limited to people with acute pain, and translation to chronic pain must still be confronted. In this Perspective, we discuss the key questions of whether more effective Nav1.8 blockers can be built and whether neural mechanisms impose a ceiling on the pain relief that can be achieved by Nav1.8 inhibition. We then explore the challenge of developing therapeutics for chronic pain and ask whether compensatory changes or development of pain generators within the CNS might limit pain relief. Finally, we discuss the clinical complexity of pain and its implications for therapy and pose questions and suggest opportunities for the future.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Targeting sodium channels — challenges for acute pain and the leap to chronic pain

  • 期刊论文

  • 发表日期：

    2025年8月15日

查看全文
  • Matthew Alsaloum,
  • Dmytro Vasylyev,
  • Stephen G. Waxman

摘要

Treatment of pain is a challenge for almost all clinicians, ranging from general practitioners to subspecialists such as pain medicine physicians, surgeons, neurologists and physiatrists. Over the past few years, clinical studies in people with acute postoperative pain have demonstrated that pain in humans can be reduced by inhibiting Nav1.8, a sodium channel that is essential for repetitive firing of peripheral pain-signalling neurons and has no essential function in the CNS. This discovery is an important step forward, but pain reduction in these studies was partial, not complete. Moreover, success via this approach thus far has been limited to people with acute pain, and translation to chronic pain must still be confronted. In this Perspective, we discuss the key questions of whether more effective Nav1.8 blockers can be built and whether neural mechanisms impose a ceiling on the pain relief that can be achieved by Nav1.8 inhibition. We then explore the challenge of developing therapeutics for chronic pain and ask whether compensatory changes or development of pain generators within the CNS might limit pain relief. Finally, we discuss the clinical complexity of pain and its implications for therapy and pose questions and suggest opportunities for the future.