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Endocannabinoids control spasticity in a multiple sclerosis model
Author(s) -
Baker David,
Pryce Gareth,
Croxford J. Ludovic,
Brown Peter,
Pertwee Roger G.,
Makriyannis Alexandros,
Khanolkar Atmaram,
Layward Lorna,
Fezza Filomena,
Bisogno Tiziana,
Marzo Vincenzo Di
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0399fje
Subject(s) - endocannabinoid system , palmitoylethanolamide , anandamide , spasticity , cannabinoid receptor , experimental autoimmune encephalomyelitis , multiple sclerosis , cannabinoid , medicine , pharmacology , neuroscience , agonist , receptor , biology , anesthesia , immunology
Spasticity is a complicating sign in multiple sclerosis that also develops in a model of chronic relapsing experimental autoimmune encephalomyelitis (CREAE) in mice. In areas associated with nerve damage, increased levels of the endocannabinoids, anandamide (arachidonoylethanolamide, AEA) and 2‐arachidonoyl glycerol (2‐AG), and of the AEA congener, palmitoylethanolamide (PEA), were detected here, whereas comparable levels of these compounds were found in normal and non‐spastic CREAE mice. While exogenously administered endocannabinoids and PEA ameliorate spasticity, selective inhibitors of endocannabinoid re‐uptake and hydrolysis—probably through the enhancement of endogenous levels of AEA, and, possibly, 2‐arachidonoyl glycerol—significantly ameliorated spasticity to an extent comparable with that observed previously with potent cannabinoid receptor agonists. These studies provide definitive evidence for the tonic control of spasticity by the endocannabinoid system and open new horizons to therapy of multiple sclerosis, and other neuromuscular diseases, based on agents modulating endocannabinoid levels and action, which exhibit little psychotropic activity.