eprintid: 1476086 rev_number: 38 eprint_status: archive userid: 608 dir: disk0/01/47/60/86 datestamp: 2016-03-03 15:33:25 lastmod: 2021-09-19 23:28:07 status_changed: 2016-03-03 15:33:25 type: article metadata_visibility: show creators_name: Minett, MS creators_name: Pereira, V creators_name: Sikandar, S creators_name: Matsuyama, A creators_name: Lolignier, S creators_name: Kanellopoulos, AH creators_name: Mancini, F creators_name: Iannetti, GD creators_name: Bogdanov, YD creators_name: Santana-Varela, S creators_name: Millet, Q creators_name: Baskozos, G creators_name: MacAllister, R creators_name: Cox, JJ creators_name: Zhao, J creators_name: Wood, JN title: Endogenous opioids contribute to insensitivity to pain in humans and mice lacking sodium channel Nav1.7 ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D09 divisions: G02 divisions: C10 divisions: D17 divisions: G95 note: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ 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. date: 2015-12-04 date_type: published official_url: http://dx.doi.org/10.1038/ncomms9967 oa_status: green full_text_type: pub pmcid: PMC4686868 language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1094485 doi: 10.1038/ncomms9967 pii: ncomms9967 language_elements: eng lyricists_name: Baskozos, Georgios lyricists_name: Cox, James lyricists_name: Iannetti, Giandomenico lyricists_name: Macallister, Raymond lyricists_name: Mancini, Flavia lyricists_name: Millet, Queensta lyricists_name: Pereira, Vanessa lyricists_name: Santana Varela, Sonia lyricists_name: Sikandar, Shafaq lyricists_name: Wood, John lyricists_name: Zhao, Jing lyricists_id: GBASK41 lyricists_id: JCOXX25 lyricists_id: GDIAN90 lyricists_id: RMCAL39 lyricists_id: FMANC34 lyricists_id: QMILL66 lyricists_id: VPERE03 lyricists_id: SSANT41 lyricists_id: SSIKA79 lyricists_id: JNWOO78 lyricists_id: JZHAO52 actors_name: Barczynska, Patrycja actors_id: PBARC91 actors_role: owner full_text_status: public publication: Nature Communications volume: 6 article_number: 8967 event_location: England issn: 2041-1723 citation: Minett, MS; Pereira, V; Sikandar, S; Matsuyama, A; Lolignier, S; Kanellopoulos, AH; Mancini, F; ... Wood, JN; + view all <#> Minett, MS; Pereira, V; Sikandar, S; Matsuyama, A; Lolignier, S; Kanellopoulos, AH; Mancini, F; Iannetti, GD; Bogdanov, YD; Santana-Varela, S; Millet, Q; Baskozos, G; MacAllister, R; Cox, JJ; Zhao, J; Wood, JN; - view fewer <#> (2015) Endogenous opioids contribute to insensitivity to pain in humans and mice lacking sodium channel Nav1.7. Nature Communications , 6 , Article 8967. 10.1038/ncomms9967 <https://doi.org/10.1038/ncomms9967>. Green open access document_url: https://discovery-pp.ucl.ac.uk/id/eprint/1476086/1/Endogenous%20opioids%20contribute%20to%20insensitivity%20to%20pain%20in%20humans%20and%20mice%20lacking%20sodium%20channel%20Nav1.7.pdf