BibTex format
@article{Farah:2025:brain/awae302,
author = {Farah, A and Patel, R and Poplawski, P and Wastie, BJ and Tseng, M and Barry, AM and Daifallah, O and Dubb, A and Paul, I and Cheng, HL and Feroz, F and Su, Y and Chan, M and Zeilhofer, HU and Price, TJ and Bennett, DL and Bannister, K and Dawes, JM},
doi = {brain/awae302},
journal = {Brain},
pages = {1001--1014},
title = {A role for leucine-rich, glioma inactivated 1 in regulating pain sensitivity.},
url = {http://dx.doi.org/10.1093/brain/awae302},
volume = {148},
year = {2025}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - 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 hype
AU - Farah,A
AU - Patel,R
AU - Poplawski,P
AU - Wastie,BJ
AU - Tseng,M
AU - Barry,AM
AU - Daifallah,O
AU - Dubb,A
AU - Paul,I
AU - Cheng,HL
AU - Feroz,F
AU - Su,Y
AU - Chan,M
AU - Zeilhofer,HU
AU - Price,TJ
AU - Bennett,DL
AU - Bannister,K
AU - Dawes,JM
DO - brain/awae302
EP - 1014
PY - 2025///
SP - 1001
TI - A role for leucine-rich, glioma inactivated 1 in regulating pain sensitivity.
T2 - Brain
UR - http://dx.doi.org/10.1093/brain/awae302
UR - https://www.ncbi.nlm.nih.gov/pubmed/39301592
VL - 148
ER -