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Enhancement of wind-up by the combined administration of adenosine A1 receptor ligands on spinalized rats with carrageenan-induced inflammation.

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.
AuthorsGuillermo Ramos-Zepeda, Juan F Herrero
JournalNeuroscience letters (Neurosci Lett) 2005 Aug 12-19 Vol. 384 Issue 1-2 Pg. 177-82 ISSN: 0304-3940 [Print] Ireland
PMID15893424 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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
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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