Pain without Nociceptors? Nav1.7-Independent Pain Mechanisms
Michael S. Minett,
Sarah Falk,
Sonia Santana-Varela,
Yury D. Bogdanov,
Mohammed A. Nassar,
Anne-Marie Heegaard,
John N. Wood
Affiliations
Michael S. Minett
Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK
Sarah Falk
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark
Sonia Santana-Varela
Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK
Yury D. Bogdanov
Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK
Mohammed A. Nassar
Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK
Anne-Marie Heegaard
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark
John N. Wood
Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK
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.
