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901 SYMPOSIUM: Molecular biology and immunology of pain
  1. Stephen G Waxman
  1. Depts. of Neurology, Neuroscience and Pharmacology, Yale Medical School and VAMC West Haven CT Chasing Men on Fire: Genes regulating pain sensibility in humans


Given the need for more effective treatments, there is a pressing need for a better understanding of chronic pain, including pain in SLE. Discovery of peripheral sodium channels (Nav1.7, Nav1.8, Nav1.9) and of pain resilience genes (KCNQ2, KCNQ3) opens up the possibility of targeting peripheral generators of pain (primary sensory neurons) without affecting the heart or CNS, thus enabling new and more effective pain therapies devoid of CNS side effects or addictive potential.

In this lecture I will review several lines of recent progress. Molecular genetics has validated peripheral sodium channels Nav1.7, 1.8 and 1.9 as strong drivers of firing of peripheral pain-signaling neurons and thus of human pain. Building upon this, recent studies have begun to provide proof of concept that Nav1.7-specific blockers can reduce pain. In parallel, genomically-guided pharmacogenomic approaches indicate that the goal of patient-specific, personalized pain therapy is an achievable objective.

Molecular genetics has also begun to identify pain resilience genes, pointing toward another set of molecular targets for pain therapy.

While there is still a lot of work to do, the goal of more effective, non-addictive treatments for chronic pain appears to be in sight.

Lay summary We are beginning to understand, in exciting detail, the molecular drivers of human pain. This new knowledge is bringing us closer to the goal of more effective, non-addictive treatments for chronic pain.

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