Julie Gardener
New Member
Endocannabinoids Control Spasticity In A Multiple Sclerosis Model
David Baker,* Gareth Pryce,* J. Ludovic Croxford,* Peter Brown,† Roger G. Pertwee, ‡ Alexandros Makriyannis, § Atmaram Khanolkar, § Lorna Layward, Filomena Fezza, # Tiziana Bisogno, # and Vincenzo Di Marzo#*Neuroinflammation Group, Institute of Neurology, University College London, U.K.; † The Medical Research Council Human Movement and Balance Unit, National Hospital for Neurology and Neurosurgery, London, U.K.; ‡ Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, U.K.; § Department of Pharmaceutical Sciences and Molecular and Cell Biology, Center for Drug Discovery, University of Connecticut, Storrs, Conn.; Multiple Sclerosis Society of Great Britain and Northern Ireland, London, U.K.; # Endocannabinoid Research Group, Instituto per la Chimica di Molecole di Interesse Biologico, Consiglio Nazionale delle Ricerche, Arco Felice, Naples, Italy.
Corresponding author: Dr. David Baker Neuroinflammation Group, Department of Neurochemistry, Institute of Neurology, University College London, 1 Wakefield Street, London, WC1N 1PJ, U.K. E-mail: d.baker@ion.ucl.ac.uk; and Dr. Vincenzo Di Marzo, Endocannabinoid Research Group, Instituto per la Chimica di Molecole di Interesse Biologico, Consiglio Nazionale delle Ricerche, via Toiano 6, 80072, Arco Felice, Naples, Italy. E-mail: vdimarzo@icmib.na.cnr.it
The FASEB Journal express article 10.1096/fj.00-0399fje. Published online December 8, 2000.
ABSTRACT
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.
Source: Endocannabinoids control spasticity in a multiple sclerosis model
