Role of adenosine receptors in spinal G-protein activation after peripheral nerve injury.
BACKGROUND
Spinally injected adenosine induces antinociception in animal models of neuropathic but not acute pain. The reasons for this discrepancy remain unclear. Adenosine receptors are coupled to G proteins, and increased efficiency of adenosine-induced G-protein activity in neuropathic pain could contribute to the antinociceptive effect of adenosine. In this study the authors used [(35)S]guanosine-5'-O-(3-thiotriphosphate) ([(35)S]GTP gamma S) autoradiography in rat spinal cord sections to test this possibility.


METHODS
The spinal cords of normal animals and those that underwent left L5 and L6 spinal nerve ligation (SNL) were removed and immediately frozen. Horizontal spinal cord sections were cut and mounted on chrom-alum gelatin-subbed slides. Sections were incubated with guanosine diphosphate, [(35)S]GTP gamma S, the adenosine A1 agonist R-N6-phenylisopropyladenosine, and various other drugs, apposed to films, and analyzed.


RESULTS
Baseline and R-N6-phenylisopropyladenosine-stimulated [(35)S]GTP gamma S binding was predominantly localized to the superficial dorsal horns of both normal and SNL animals. This binding was significantly increased in SNL compared with normal animals. In contrast, no difference in R-N6-phenylisopropyladenosine-stimulated [(35)S]GTP gamma S binding was observed between SNL and normal animals. Blockade of adenosine A1 receptors by 1,3-dipropyl-8-cyclopentylxanthine, or adenosine destruction by added adenosine deaminase, reduced the increased basal activity in SNL to baseline levels of normal dorsal horns, whereas atropine and naloxone had no effect.


CONCLUSIONS
This study shows an increased basal G-protein activity in lumbar spinal cords during conditions of SNL. The data suggest that increased adenosine release during conditions of SNL results in an increased basal activity of G proteins in the spinal cord during neuropathic pain.
Bantel
Carsten
C
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Childers
Steven R
SR
Eisenach
James C
JC
D000241:Adenosine / Q000502:physiology; D000818:Animals; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D013127:Spinal Nerves / Q000293:injuries*
D018047:Receptors, Purinergic P1; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019204:GTP-Binding Proteins; D000241:Adenosine