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Pain without nociceptors? Nav1.7-independent pain mechanisms

Pain without nociceptors? Nav1.7-independent pain mechanisms
Pain without nociceptors? Nav1.7-independent pain mechanisms

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.

2211-1247
301-312
Minett, Michael S.
d767767a-4b0f-4090-a715-70a936fc37c6
Falk, Sarah
3b700c39-26ca-4c96-bb6e-a892e7e22fac
Santana-Varela, Sonia
da067c0f-bfc4-4a5a-8f54-2e28b5c3bcde
Bogdanov, Yury D.
0c970999-e191-4f1b-90d9-7bf25a5d5b4b
Nassar, Mohammed A.
f7eb6257-ec39-48b9-a587-d5dd53631b0c
Heegaard, Anne Marie
bcc7e37e-f391-4b36-a110-dc0ad6e135a3
Wood, John N.
afbfb1c4-d021-4f51-88d2-9e481532b797
Minett, Michael S.
d767767a-4b0f-4090-a715-70a936fc37c6
Falk, Sarah
3b700c39-26ca-4c96-bb6e-a892e7e22fac
Santana-Varela, Sonia
da067c0f-bfc4-4a5a-8f54-2e28b5c3bcde
Bogdanov, Yury D.
0c970999-e191-4f1b-90d9-7bf25a5d5b4b
Nassar, Mohammed A.
f7eb6257-ec39-48b9-a587-d5dd53631b0c
Heegaard, Anne Marie
bcc7e37e-f391-4b36-a110-dc0ad6e135a3
Wood, John N.
afbfb1c4-d021-4f51-88d2-9e481532b797

Minett, Michael S., Falk, Sarah, Santana-Varela, Sonia, Bogdanov, Yury D., Nassar, Mohammed A., Heegaard, Anne Marie and Wood, John N. (2014) Pain without nociceptors? Nav1.7-independent pain mechanisms. Cell Reports, 6 (2), 301-312. (doi:10.1016/j.celrep.2013.12.033).

Record type: Article

Abstract

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.

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More information

Accepted/In Press date: 20 December 2013
e-pub ahead of print date: 16 January 2014
Published date: 30 January 2014

Identifiers

Local EPrints ID: 417212
URI: http://eprints.soton.ac.uk/id/eprint/417212
ISSN: 2211-1247
PURE UUID: ba2c0115-0b88-455f-87c3-69cf37e149e3
ORCID for Yury D. Bogdanov: ORCID iD orcid.org/0000-0003-4667-5890

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Date deposited: 25 Jan 2018 17:30
Last modified: 18 Feb 2021 17:25

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Contributors

Author: Michael S. Minett
Author: Sarah Falk
Author: Sonia Santana-Varela
Author: Mohammed A. Nassar
Author: Anne Marie Heegaard
Author: John N. Wood

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