RT Journal Article
SR Electronic
T1 Allosteric Adenosine Receptor Modulation Reduces Hypersensitivity Following Peripheral Inflammation by a Central Mechanism
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 950
OP 955
DO 10.1124/jpet.102.047951
VO 305
IS 3
A1 Xinhui Li
A1 Dawn Conklin
A1 Hui-Lin Pan
A1 James C. Eisenach
YR 2003
UL http://jpet.aspetjournals.org/content/305/3/950.abstract
AB Activation of adenosine A1 receptors by endogenous adenosine or synthetic agonists produces antinociception in animal models of acute pain and also reduces hypersensitivity in models of inflammatory and nerve-injury pain. Allosteric adenosine modulators facilitate and potentate the action of adenosine agonists at the A1 receptors. The purpose of the current study was to examine the effect and site of action for an allosteric adenosine modulator, T62 [2-amino-3-(4-chlorobenzoyl)-5,6, 7,8-tetrahydrobenzothiophene], in rat models of acute pain and inflammation. Intrathecal (i.t.) T62 did not change the withdrawal latency or threshold of normal rats to acute heat or to acute paw pressure. In contrast, i.t. T62 reversed thermal hypersensitivity in carrageenin-inflamed rats. Subcutaneous (s.c.) injection of T62 into the inflamed paw had no such effect. To investigate a potential site of action on nociceptors, single-unit afferent activity to mechanical stimuli on Aδ- and C-fibers was examined in normal or carrageenin-inflamed rats before and after intravenous (i.v.) T62 administration. Intravenous T62, 3 mg/kg, had no significant effect in either normal or inflamed conditions. These results support previous studies to suggest that adenosine receptor modulators lack efficacy to acute nociceptive stimuli in the normal condition, but reduce hypersensitivity during inflammation through a central mechanism. The American Society for Pharmacology and Experimental Therapeutics