title: 5'-Chloro-5'-deoxy-(±)-ENBA, a potent and selective adenosine A(1) receptor agonist, alleviates neuropathic pain in mice through functional glial and microglial changes without affecting motor or cardiovascular functions.
abstract: This study was undertaken in order to investigate the effect of chronic treatment with 5&#8242;-chloro-5&#8242;-deoxy-(&#177;)-ENBA, a potent and highly selective agonist of human adenosine A(1) receptor, on thermal hyperalgesia and mechanical allodynia in a mouse model of neuropathic pain, the Spared Nerve Injury (SNI) of the sciatic nerve. Chronic systemic administration of 5&#8242;-chloro-5&#8242;-deoxy-(&#177;)-ENBA (0.5 mg/kg, i.p.) reduced both mechanical allodynia and thermal hyperalgesia 3 and 7 days post-SNI, in a way prevented by DPCPX (3 mg/kg, i.p.), a selective A(1) adenosine receptor antagonist, without exerting any significant change on the motor coordination or arterial blood pressure. In addition, a single intraperitoneal injection of 5&#8242;-chloro-5&#8242;-deoxy-(&#177;)-ENBA (0.5 mg/kg, i.p.) 7 days post-SNI also reduced both symptoms for at least two hours. SNI was associated with spinal changes in microglial activation ipsilaterally to the nerve injury. Activated, hypertrophic microglia were significantly reduced by 5&#8242;-chloro-5&#8242;-deoxy-(&#177;)-ENBA chronic treatment. Our results demonstrated an involvement of adenosine A(1) receptor in the amplified nociceptive thresholds and in spinal glial and microglial changes occurred in neuropathic pain, without affecting motor coordination or blood pressure. Our data suggest a possible use of adenosine A(1) receptor agonist in neuropathic pain symptoms.
authors.affiliation: Section of Pharmacology L. Donatelli, Department of Experimental Medicine, Faculty of Medicine and Surgery, II University of Naples, via Costantinopoli 16, 80138 Naples, Italy. livio.luongo@gmail.com
authors.forename: Livio
authors.initials: L
authors.lastname: Luongo
authors.forename: Riccardo
authors.initials: R
authors.lastname: Petrelli
authors.forename: Luisa
authors.initials: L
authors.lastname: Gatta
authors.forename: Catia
authors.initials: C
authors.lastname: Giordano
authors.forename: Francesca
authors.initials: F
authors.lastname: Guida
authors.forename: Patrizia
authors.initials: P
authors.lastname: Vita
authors.forename: Palmarisa
authors.initials: P
authors.lastname: Franchetti
authors.forename: Mario
authors.initials: M
authors.lastname: Grifantini
authors.forename: Vito
authors.initials: V
authors.lastname: de Novellis
authors.forename: Loredana
authors.initials: L
authors.lastname: Cappellacci
authors.forename: Sabatino
authors.initials: S
authors.lastname: Maione
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D058907:Adenosine A1 Receptor Agonists / Q000008:administration & dosage*; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D009437:Neuralgia / Q000188:drug therapy*; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009636:Norbornanes / Q000008:administration & dosage*; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries; D014970:Xanthines / Q000008:administration & dosage
chemical_list: D058907:Adenosine A1 Receptor Agonists; C089285:N(6)-(2-endo-norbornyl)adenosine; D009636:Norbornanes; D043682:Receptor, Adenosine A1; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine