title: Spinal vs. supraspinal antinociceptive activity of the adenosine A(1) receptor agonist cyclopentyl-adenosine in rats with inflammation.
abstract: The adenosine A(1) receptor is involved in spinal cord antinociception. As its role at supraspinal sites is not well known, we studied the systemic effects of its agonist N-cyclopentyl-adenosine (CPA) in single motor units from adult-spinalized, intact and sham-spinalized rats. CPA was not effective after spinalization, but it was very effective in intact animals (ID50: 92+/-1.3 microg/kg, noxious pinch) and over 10-fold more potent in sham-spinalized animals (ID50 of 8.3+/-1 microg/kg). Wind-up was also inhibited by CPA. We also studied the effect of CPA in the immature spinal cord preparation, where CPA dose-dependently inhibited responses to low (IC50s: 9+/-0.7 and 7.7+/-1.3 nM) and high intensity stimulation (IC50s: 4.9+/-0.5 and 12.1+/-2 nM). We conclude that the integrity of the spinal cord is crucial for the antinociceptive activity of systemic CPA in adult rats but not in immature rats, not yet influenced by a completely developed supraspinal control.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad de Alcalá, Alcalá de Henares, 28871 Madrid, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Ramos-Zepeda
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schröder
authors.forename: Silke
authors.initials: S
authors.lastname: Rosenow
authors.forename: Juan F
authors.initials: JF
authors.lastname: Herrero
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D019054:Evoked Potentials, Motor / Q000187:drug effects; D005260:Female; D006930:Hyperalgesia / Q000503:physiopathology / Q000517:prevention & control; D066298:In Vitro Techniques; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000502:physiology; D012023:Reflex, Monosynaptic / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000503:physiopathology; D013314:Stress, Mechanical; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D000700:Analgesics; D043682:Receptor, Adenosine A1; C053907:8-cyclopentyl-1,3-dimethylxanthine; C048599:N(6)-cyclopentyladenosine; D013806:Theophylline; D000241:Adenosine