CUED Publications database

Endogenous opioids contribute to insensitivity to pain in humans and mice lacking sodium channel Nav1.7.

Minett, MS and Pereira, V and Sikandar, S and Matsuyama, A and Lolignier, S and Kanellopoulos, AH and Mancini, F and Iannetti, GD and Bogdanov, YD and Santana-Varela, S and Millet, Q and Baskozos, G and MacAllister, R and Cox, JJ and Zhao, J and Wood, JN (2015) Endogenous opioids contribute to insensitivity to pain in humans and mice lacking sodium channel Nav1.7. Nat Commun, 6. 8967-.

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Abstract

Loss-of-function mutations in the SCN9A gene encoding voltage-gated sodium channel Nav1.7 cause congenital insensitivity to pain in humans and mice. Surprisingly, many potent selective antagonists of Nav1.7 are weak analgesics. We investigated whether Nav1.7, as well as contributing to electrical signalling, may have additional functions. Here we report that Nav1.7 deletion has profound effects on gene expression, leading to an upregulation of enkephalin precursor Penk mRNA and met-enkephalin protein in sensory neurons. In contrast, Nav1.8-null mutant sensory neurons show no upregulated Penk mRNA expression. Application of the opioid antagonist naloxone potentiates noxious peripheral input into the spinal cord and dramatically reduces analgesia in both female and male Nav1.7-null mutant mice, as well as in a human Nav1.7-null mutant. These data suggest that Nav1.7 channel blockers alone may not replicate the analgesic phenotype of null mutant humans and mice, but may be potentiated with exogenous opioids.

Item Type: Article
Uncontrolled Keywords: Adult Animals Enkephalins Female Humans Male Mice Mice, Knockout NAV1.7 Voltage-Gated Sodium Channel Pain Insensitivity, Congenital Sensation Sensory Receptor Cells
Subjects: UNSPECIFIED
Divisions: Div F > Computational and Biological Learning
Depositing User: Cron Job
Date Deposited: 17 Jul 2017 18:59
Last Modified: 12 Sep 2017 01:21
DOI: