Imperial College London
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ProfessorYuriKorchev

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor of Biophysics
 
 
 
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Contact

 

+44 (0)20 3313 3080y.korchev

 
 
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Location

 

BN5, Nanomedicine LabCommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Anand:2020,
author = {Anand, U and Jones, B and Korchev, Y and Bloom, S and Pacchetti, B and Anand, P and Sodergren, M},
journal = {Journal of Pain Research},
pages = {2269--2278},
title = {CBD effects on TRPV1 signaling pathways in cultured DRG neurons},
url = {http://hdl.handle.net/10044/1/82342},
volume = {2020},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Introduction: Cannabidiol (CBD) is reported to produce pain relief, but the clinically relevant cellular and molecular mechanisms remain uncertain.  The TRPV1 receptor integrates noxious stimuli and plays a key role in pain signaling.  Hence, we conducted in vitro studies, to elucidate the efficacy and mechanisms of CBD for inhibiting neuronal hypersensitivity in cultured rat sensory neurons, following activation of TRPV1.  Methods: Adult rat dorsal root ganglion (DRG) neurons were cultured, and supplemented with the neurotrophic factors NGF and GDNF, in an established model of neuronal hypersensitivity. 48 h after plating, neurons were stimulated with CBD (Adven 150, EMMAC Life Sciences) at 1, 10, 100 nMol/L and 1, 10 and 50 µMol/L.  In separate experiments, DRG neurons were also stimulated with capsaicin with or without CBD (1 nMol/L to10 µMol/L), in a functional calcium imaging assay.  The effects of the adenylyl cyclase activator forskolin and the calcineurin inhibitor cyclosporin were determined.  We also measured forskolin-stimulated cAMP levels, without and after treatment with CBD, using a homogenous time resolved fluorescence (HTRF) assay. The results were analysed using Student’s t-test. Results:  DRG neurons treated with 10 and 50 µMol/L CBD showed calcium influx, but not at lower doses. Neurons treated with capsaicin demonstrated robust calcium influx, which was dose-dependently reduced in the presence of low dose CBD (IC50 = 100 nMol/L).  The inhibition or desensitization by CBD was reversed in the presence of forskolin and cyclosporin.  Forskolin stimulated cAMP levels were significantly reduced in CBD treated neurons.Conclusions: CBD at low doses corresponding to plasma concentrations observed physiologically, inhibits or desensitizes neuronal TRPV1 signalling by inhibiting the adenylyl cyclase – cAMP pathway, which is essential for maintaining TRPV1 phosphorylation and sensitization.  CBD also facilitated calcineurin-med
AU  - Anand,U
AU  - Jones,B
AU  - Korchev,Y
AU  - Bloom,S
AU  - Pacchetti,B
AU  - Anand,P
AU  - Sodergren,M
EP  - 2278
PY  - 2020///
SN  - 1178-7090
SP  - 2269
TI  - CBD effects on TRPV1 signaling pathways in cultured DRG neurons
T2  - Journal of Pain Research
UR  - http://hdl.handle.net/10044/1/82342
VL  - 2020
ER  -
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