title: Changes in spinal and supraspinal endocannabinoid levels in neuropathic rats.
abstract: Recent studies have shown that activation of the cannabinoid CB(1) receptor by synthetic agonists, and pharmacological elevation of endocannabinoid levels, suppress hyperalgesia and allodynia in animal models of neuropathic pain. However, the concentrations of endocannabinoids in the nervous tissues involved in pain transmission during neuropathic pain have never been measured. Here we have determined the levels of anandamide and 2-arachidonoylglycerol (2-AG), as well as of the analgesic anandamide congener, palmitoylethanolamide (PEA), in three brain areas involved in nociception, i.e. the dorsal raphe (DR), periaqueductal grey (PAG) and rostral ventral medulla (RVM), as well as in the spinal cord (SC), following chronic constriction injury (CCI) of the sciatic nerve in the rat, in comparison with sham-operated rats. After 3 days from CCI, anandamide or 2-AG levels were significantly enhanced only in the SC or PAG, respectively. After 7 days from CCI, when thermal hyperalgesia and mechanical allodynia are maximal, a strong (1.3-3-fold) increase of both anandamide and 2-AG levels was observed in the PAG, RVM and SC. At this time point, anandamide, but not 2-AG, levels were also enhanced in the DR. PEA levels were significantly decreased in the SC after 3 days, and in the DR and RVM after 7 days from CCI. These data indicate that anandamide and 2-AG, operating at both spinal and supra-spinal levels, are up-regulated during CCI of the sciatic nerve, possibly to inhibit pain. Yet to be developed substances that inhibit both endocannabinoid and PEA inactivation might be useful for the treatment of neuropathic pain.
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche (C.N.R.), Via Dei Campi Flegrei 34, Comprensorio Olivetti, Pozzuoli, Naples 80078, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrosino
authors.forename: Enza
authors.initials: E
authors.lastname: Palazzo
authors.forename: Vito
authors.initials: V
authors.lastname: de Novellis
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bisogno
authors.forename: Francesco
authors.initials: F
authors.lastname: Rossi
authors.forename: Sabatino
authors.initials: S
authors.lastname: Maione
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D004195:Disease Models, Animal; D063388:Endocannabinoids; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000502:physiology; D012585:Sciatica / Q000378:metabolism* / Q000473:pathology*; D013116:Spinal Cord / Q000378:metabolism*; D013997:Time Factors
chemical_list: D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids