Evidence map›Paper›PMID 39301592›Full record

ArticleBrain : a journal of neurology2025

A role for leucine-rich, glioma inactivated 1 in regulating pain sensitivity.

Adham Farah, Ryan Patel, Piotr Poplawski, Benjamin J Wastie, Mandy Tseng, Allison M Barry, Omar Daifallah, Akash Dubb, Ivan Paul, Hoi Lao Cheng and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain : a journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Recent advances in autoantibody-mediated pain.Current opinion in supportive and palliative care · 2026
    Review
  2. Article
  3. Autoantibodies as drivers of neuropathic pain.Trends in molecular medicine · 2026
    Review
  4. Article
  5. Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Adham FarahNuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Ryan PatelWolfson Sensory, Pain & Regeneration Centre, Guy's Campus, Kings College London, London SE1 1UL, UK.
Piotr PoplawskiNuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Benjamin J WastieNuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Mandy TsengNuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Allison M BarryCenter for Advanced Pain Studies, School of Behavioral and Brain Sciences, Department of Neuroscience, University of Texas at Dallas, Richardson, TX 75080, USA.
Omar DaifallahNuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Akash DubbNuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Ivan PaulNuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Hoi Lao ChengNuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Faisal FerozNuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Yuhe SuNuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Marva ChanNuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Hanns Ulrich ZeilhoferInstitute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland.
Theodore J PriceCenter for Advanced Pain Studies, School of Behavioral and Brain Sciences, Department of Neuroscience, University of Texas at Dallas, Richardson, TX 75080, USA.ORCID 0000-0002-6971-6221
David L BennettNuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.ORCID 0000-0002-7996-2696
Kirsty BannisterWolfson Sensory, Pain & Regeneration Centre, Guy's Campus, Kings College London, London SE1 1UL, UK.ORCID 0000-0002-3043-3574
John M DawesNuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.

Funding

Medical Research Council MR/V003534/1MRC MR/V003534/1
6 · The paper itself

Abstract

Neuronal hyperexcitability is a key driver of persistent pain states, including neuropathic pain. Leucine-rich, glioma inactivated 1 (LGI1) is a secreted protein known to regulate excitability within the nervous system and is the target of autoantibodies from neuropathic pain patients. Therapies that block or reduce antibody levels are effective at relieving pain in these patients, suggesting that LGI1 has an important role in clinical pain. Here we have investigated the role of LGI1 in regulating neuronal excitability and pain-related sensitivity by studying the consequences of genetic ablation in specific neuron populations using transgenic mouse models. LGI1 has been well studied at the level of the brain, but its actions in the spinal cord and peripheral nervous system are poorly understood. We show that LGI1 is highly expressed in dorsal root ganglion (DRG) and spinal cord dorsal horn neurons in both mouse and human. Using transgenic mouse models, we genetically ablated LGI1, either specifically in nociceptors (LGI1fl/Nav1.8+) or in both DRG and spinal neurons (LGI1fl/Hoxb8+). On acute pain assays, we found that loss of LGI1 resulted in mild thermal and mechanical pain-related hypersensitivity when compared with littermate controls. In LGI1fl/Hoxb8+ mice, we found loss of Kv1 currents and hyperexcitability of DRG neurons. LGI1fl/Hoxb8+ mice displayed a significant increase in nocifensive behaviours in the second phase of the formalin test (not observed in LGI1fl/Nav1.8+ mice), and extracellular recordings in LGI1fl/Hoxb8+ mice revealed hyperexcitability in spinal dorsal horn neurons, including enhanced wind-up. Using the spared nerve injury model, we found that LGI1 expression was dysregulated in the spinal cord. LGI1fl/Nav1.8+ mice showed no differences in nerve injury-induced mechanical hypersensitivity, brush-evoked allodynia or spontaneous pain behaviour compared with controls. However, LGI1fl/Hoxb8+ mice showed a significant exacerbation of mechanical hypersensitivity and allodynia. Our findings point to effects of LGI1 at the level of both the DRG and the spinal cord, including an important impact of spinal LGI1 on pathological pain. Overall, we find a novel role for LGI1 with relevance to clinical pain.

Indexed as

NeuralgiaPainPain ThresholdProteinsAnimalsDisease Models, AnimalFemaleGanglia, SpinalHumansHyperalgesiaIntracellular Signaling Peptides and ProteinsMaleMiceMice, Inbred C57BLMice, TransgenicNociceptorsIntracellular Signaling Peptides and ProteinsLGI1 protein, humanLgi1 protein, mouseProteinshyperexcitabilityleucine-rich, glioma inactivated 1 (LGI1)mechanical pain hypersensitivityneuropathic painwind-up

Identifiers

PMID39301592
PMCPMC11884686

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Registered trials

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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.