ArticleMolecular pain2008
Paroxysmal extreme pain disorder M1627K mutation in human Nav1.7 renders DRG neurons hyperexcitable.
Article in Molecular pain, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 citations in OpenAlex.
- Gene variant effects across sodium channelopathies predict function and guide precision therapy.Brain : a journal of neurology · 2022Pooled it
- Shaping the Action Potential in Dorsal Root and Trigeminal Ganglia Neurons: Relevance to Pain Mechanisms.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- Article
- Sculpting excitable membranes: voltage-gated ion channel delivery and distribution.Nature reviews. Neuroscience · 2025Review
- Voltage-Gated Ion Channels in Neuropathic Pain Signaling.Life (Basel, Switzerland) · 2025Review
- The evolution of patch-clamp electrophysiology: Robotic, multiplex, and dynamic.Molecular pharmacology · 2025Review
- Peripheral temperature dysregulation associated with functionally altered NaPflugers Archiv : European journal of physiology · 2023Article
- Cold and warmth intensify pain-linked sodium channel gating effects and persistent currents.The Journal of general physiology · 2023Article
- Peripheral mechanisms of peripheral neuropathic pain.Frontiers in molecular neuroscience · 2023Review
- Beyond CBD: Inhibitory effects of lesser studied phytocannabinoids on human voltage-gated sodium channels.Frontiers in physiology · 2023Article
- Pain triangle phenomenon in possible association with SCN9A: A case report.Molecular genetics & genomic medicine · 2022Article
- E44Q mutation in NaHeliyon · 2021Article
- The physiological function of different voltage-gated sodium channels in pain.Nature reviews. Neuroscience · 2021Review
- Hydropathicity-based prediction of pain-causing NaV1.7 variants.BMC bioinformatics · 2021Article
- Non-extensitivity and criticality of atomic hydropathicity around a voltage-gated sodium channel's pore: a modeling study.Journal of biological physics · 2021Article
- HDAC6: A Key Link Between Mitochondria and Development of Peripheral Neuropathy.Frontiers in molecular neuroscience · 2021Review
- Pain-related toxins in scorpion and spider venoms: a face to face with ion channels.The journal of venomous animals and toxins including tropical diseases · 2021Review
- Computational pipeline to probe NaV1.7 gain-of-function variants in neuropathic painful syndromes.Scientific reports · 2020Article
- Paroxysmal extreme pain disorder in family with c.3892G > T (p.Val1298Phe) in the SCN9A gene mutation - case report.BMC neurology · 2020Article
- Bisphenol A Regulates Sodium Ramp Currents in Mouse Dorsal Root Ganglion Neurons and Increases Nociception.Scientific reports · 2019Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundParoxysmal extreme pain disorder (PEPD) is an autosomal dominant painful neuropathy with many, but not all, cases linked to gain-of-function mutations in SCN9A which encodes voltage-gated sodium channel Nav1.7. Severe pain episodes and skin flushing start in infancy and are induced by perianal probing or bowl movement, and pain progresses to ocular and mandibular areas with age. Carbamazepine has been effective in relieving symptoms, while other drugs including other anti-epileptics are less effective.
resultsSequencing of SCN9A coding exons from an English patient, diagnosed with PEPD, has identified a methionine 1627 to lysine (M1627K) substitution in the linker joining segments S4 and S5 in domain IV. We confirm that M1627K depolarizes the voltage-dependence of fast-inactivation without substantially altering activation or slow-inactivation, and inactivates from the open state with slower kinetics. We show here that M1627K does not alter development of closed-state inactivation, and that M1627K channels recover from fast-inactivation faster than wild type channels, and produce larger currents in response to a slow ramp stimulus. Using current-clamp recordings, we also show that the M1627K mutant channel reduces the threshold for single action potentials in DRG neurons and increases the number of action potentials in response to graded stimuli.
conclusionM1627K mutation was previously identified in a sporadic case of PEPD from France, and we now report it in an English family. We confirm the initial characterization of mutant M1627K effect on fast-inactivation of Nav1.7 and extend the analysis to other gating properties of the channel. We also show that M1627K mutant channels render DRG neurons hyperexcitable. Our new data provide a link between altered channel biophysics and pain in PEPD patients.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.