Abstract |
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.
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Authors | Guillermo Ramos-Zepeda, Juan F Herrero |
Journal | Neuroscience letters
(Neurosci Lett)
2005 Aug 12-19
Vol. 384
Issue 1-2
Pg. 177-82
ISSN: 0304-3940 [Print] Ireland |
PMID | 15893424
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Drug Combinations
- Narcotic Antagonists
- Purinergic P1 Receptor Agonists
- Purinergic P1 Receptor Antagonists
- 8-cyclopentyl-1,3-dimethylxanthine
- Naloxone
- N(6)-cyclopentyladenosine
- Carrageenan
- Theophylline
- Adenosine
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Topics |
- Adenosine
(administration & dosage, analogs & derivatives)
- Animals
- Carrageenan
(toxicity)
- Drug Combinations
- Drug Interactions
- Inflammation
(chemically induced, complications, drug therapy)
- Male
- Naloxone
(pharmacology)
- Narcotic Antagonists
(pharmacology)
- Physical Stimulation
(methods)
- Purinergic P1 Receptor Agonists
- Purinergic P1 Receptor Antagonists
- Rats
- Rats, Wistar
- Reflex
(drug effects, radiation effects)
- Spinal Cord Injuries
(complications, drug therapy)
- Theophylline
(administration & dosage, analogs & derivatives)
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