Enhancement of wind-up by the combined administration of adenosine A1 receptor ligands on spinalized rats with carrageenan-induced inflammation.
The adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) is very effective in reducing wind-up in intact but not in spinalized adult rats with carrageenan-induced inflammation, suggesting an adenosine-mediated supraspinal modulation. Since wind-up is a spinal cord mediated phenomenon but highly influenced by descending modulatory systems, especially in situations of sensitization, we assessed the possible involvement of adenosine in the modulation of wind-up. We studied the effect of the adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT) in the presence and in the absence of the adenosine A(1) receptor agonist CPA. The experiments were carried out in spinalized male Wistar rats under alpha-chloralose anaesthesia. Withdrawal reflexes, studied as single motor units, were activated by noxious mechanical and high-intensity repetitive electrical stimulation (wind-up). While CPA and CPT were not able to induce any change on wind-up when injected alone, the combination of the two drugs, in any order, lead to an important enhancement of wind-up. This enhancement not always paralleled an increase of responses to noxious mechanical stimulation, indicating that the effect is mainly located in the spinal cord. In addition, the enhancement of wind-up was not further increased by the administration of the opioid receptor antagonist naloxone. We conclude that the depression of the wind-up phenomenon observed in spinalized animals is, at least in part, dependent of adenosine systems and can be relieved by the combined administration of CPA and CPT.
Ramos-Zepeda
Guillermo
G
Departamento de Fisiología, Campus Universitario, Universidad de Alcalá, Alcalá de Henares, 28871 Madrid, Spain.
Herrero
Juan F
JF
D000241:Adenosine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000818:Animals; D002351:Carrageenan / Q000633:toxicity; D004338:Drug Combinations; D004347:Drug Interactions; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010812:Physical Stimulation / Q000379:methods; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects* / Q000528:radiation effects; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy*; D013806:Theophylline / Q000008:administration & dosage* / Q000031:analogs & derivatives*
D004338:Drug Combinations; D009292:Narcotic Antagonists; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; C053907:8-cyclopentyl-1,3-dimethylxanthine; D009270:Naloxone; C048599:N(6)-cyclopentyladenosine; D002351:Carrageenan; D013806:Theophylline; D000241:Adenosine