Cell Reports
Volume 6, Issue 2, 30 January 2014, Pages 301-312
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Article
Pain without Nociceptors? Nav1.7-Independent Pain Mechanisms

https://doi.org/10.1016/j.celrep.2013.12.033Get rights and content
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Highlights

  • Phenotypically identical pain models have different underlying molecular mechanisms

  • Nav1.7 expression is required for sympathetic sprouting after neuronal damage

  • Oxaliplatin and cancer-induced bone pain are both Nav1.7-independent

  • Deleting Nav1.7 in adult mice reverses nerve damage-induced neuropathic pain

Summary

Nav1.7, a peripheral neuron voltage-gated sodium channel, is essential for pain and olfaction in mice and humans. We examined the role of Nav1.7 as well as Nav1.3, Nav1.8, and Nav1.9 in different mouse models of chronic pain. Constriction-injury-dependent neuropathic pain is abolished when Nav1.7 is deleted in sensory neurons, unlike nerve-transection-related pain, which requires the deletion of Nav1.7 in sensory and sympathetic neurons for pain relief. Sympathetic sprouting that develops in parallel with nerve-transection pain depends on the presence of Nav1.7 in sympathetic neurons. Mechanical and cold allodynia required distinct sets of neurons and different repertoires of sodium channels depending on the nerve injury model. Surprisingly, pain induced by the chemotherapeutic agent oxaliplatin and cancer-induced bone pain do not require the presence of Nav1.7 sodium channels or Nav1.8-positive nociceptors. Thus, similar pain phenotypes arise through distinct cellular and molecular mechanisms. Therefore, rational analgesic drug therapy requires patient stratification in terms of mechanisms and not just phenotype.

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