Alterations of the endocannabinoid system in an animal model of migraine: evaluation in cerebral areas of rat
R Greco
IRCCS Neurological Institute ‘C. Mondino Foundation’,
University Centre for the Study of Adaptive Disorder and Headache (UCADH), University of Pavia, Pavia,
Search for more papers by this authorV Gasperi
Department of Experimental Medicine and Biochemical Sciences & ‘Mondino-Tor Vergata’ Centre for Experimental Neurobiology, University of Tor Vergata,
Search for more papers by this authorG Sandrini
IRCCS Neurological Institute ‘C. Mondino Foundation’,
University Centre for the Study of Adaptive Disorder and Headache (UCADH), University of Pavia, Pavia,
Search for more papers by this authorG Bagetta
Department of Pharmacobiology and University Centre for the Study of Adaptive Disorder and Headache (UCADH), Section of Neuropharmacology of Normal and Pathological Neuronal Plasticity, University of Calabria, Rende (CS) and
Search for more papers by this authorG Nappi
IRCCS Neurological Institute ‘C. Mondino Foundation’,
University Centre for the Study of Adaptive Disorder and Headache (UCADH), University of Pavia, Pavia,
Department of Neurology and Otorhinolaryngology, University of Rome ‘La Sapienza’, Rome,
Search for more papers by this authorM Maccarrone
Department of Biomedical Sciences, University of Teramo, Teramo, Italy
Search for more papers by this authorCorresponding Author
C Tassorelli
IRCCS Neurological Institute ‘C. Mondino Foundation’,
University Centre for the Study of Adaptive Disorder and Headache (UCADH), University of Pavia, Pavia,
Cristina Tassorelli MD, PhD, IRCCS ‘C. Mondino Institute of Neurology’ Foundation, Via Mondino, 2, 27100 Pavia, Italy. Tel. + 0039-0382-38-0479, fax + 0039-0382-38-0286, e-mail [email protected]Search for more papers by this authorR Greco
IRCCS Neurological Institute ‘C. Mondino Foundation’,
University Centre for the Study of Adaptive Disorder and Headache (UCADH), University of Pavia, Pavia,
Search for more papers by this authorV Gasperi
Department of Experimental Medicine and Biochemical Sciences & ‘Mondino-Tor Vergata’ Centre for Experimental Neurobiology, University of Tor Vergata,
Search for more papers by this authorG Sandrini
IRCCS Neurological Institute ‘C. Mondino Foundation’,
University Centre for the Study of Adaptive Disorder and Headache (UCADH), University of Pavia, Pavia,
Search for more papers by this authorG Bagetta
Department of Pharmacobiology and University Centre for the Study of Adaptive Disorder and Headache (UCADH), Section of Neuropharmacology of Normal and Pathological Neuronal Plasticity, University of Calabria, Rende (CS) and
Search for more papers by this authorG Nappi
IRCCS Neurological Institute ‘C. Mondino Foundation’,
University Centre for the Study of Adaptive Disorder and Headache (UCADH), University of Pavia, Pavia,
Department of Neurology and Otorhinolaryngology, University of Rome ‘La Sapienza’, Rome,
Search for more papers by this authorM Maccarrone
Department of Biomedical Sciences, University of Teramo, Teramo, Italy
Search for more papers by this authorCorresponding Author
C Tassorelli
IRCCS Neurological Institute ‘C. Mondino Foundation’,
University Centre for the Study of Adaptive Disorder and Headache (UCADH), University of Pavia, Pavia,
Cristina Tassorelli MD, PhD, IRCCS ‘C. Mondino Institute of Neurology’ Foundation, Via Mondino, 2, 27100 Pavia, Italy. Tel. + 0039-0382-38-0479, fax + 0039-0382-38-0286, e-mail [email protected]Search for more papers by this authorR.G. and V.G. contributed equally to this work.
Abstract
Endocannabinoids are involved in the modulation of pain and hyperalgesia. In this study we investigated the role of the endocannabinoid system in the migraine model based on nitroglycerin-induced hyperalgesia in the rat. Male rats were injected with nitroglycerin (10 mg/kg, i.p.) or vehicle and sacrificed 4 h later. The medulla, the mesencephalon and the hypothalamus were dissected out and utilized for the evaluation of activity of fatty acid amide hydrolase (that degrades the endocannabinoid anandamide), monoacylglycerol lipase (that degrades the endocannabinoid 2-arachidonoylglycerol), and binding sites specific for cannabinoid (CB) receptors. The findings obtained show that nitroglycerin-induced hyperalgesia is associated with increased activity of both hydrolases and increased density of CB binding sites in the mesencephalon. In the hypothalamus we observed an increase in the activity of fatty acid amide hydrolase associated with an increase in density of CB binding sites, while in the medulla only the activity of fatty acid amide hydrolase was increased. Anandamide also proved effective in preventing nitroglycerin-induced activation (c-Fos) of neurons in the nucleus trigeminalis caudalis. These data strongly support the involvement of the endocannabinoid system in the modulation of nitroglycerin-induced hyperalgesia, and, possibly, in the pathophysiological mechanisms of migraine.
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