TY - JOUR
T1 - Pain without nociceptors?
T2 - Nav1.7-independent pain mechanisms
AU - Minett, Michael S
AU - Falk, Sarah
AU - Santana-Varela, Sonia
AU - Bogdanov, Yury D
AU - Nassar, Mohammed A
AU - Heegaard, Anne-Marie
AU - Wood, John N
N1 - Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2014/1/30
Y1 - 2014/1/30
N2 - 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 inparallel with nerve-transection pain depends on thepresence 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.
AB - 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 inparallel with nerve-transection pain depends on thepresence 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.
U2 - 10.1016/j.celrep.2013.12.033
DO - 10.1016/j.celrep.2013.12.033
M3 - Journal article
C2 - 24440715
SN - 2639-1856
VL - 6
SP - 245
EP - 246
JO - Cell Reports
JF - Cell Reports
IS - 2
ER -
