title: Chronic activation of spinal adenosine A1 receptors results in hypersensitivity.
abstract: Spinally administered adenosine reduces hypersensitivity in animals and humans with nerve injury, but also causes transient pain in humans and reduces tonic inhibition in spinal neurons. Nerve injury results in increased tonic spinal cord adenosine A1 receptor activation, consistent with a role for adenosine to generate hypersensitivity. Here, we demonstrate that chronic intrathecal adenosine induces hypersensitivity in normal animals and that chronic blockade of spinal adenosine A1 receptors by the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine partially prevents nerve injury-induced hypersensitivity. In contrast, chronic blockade of spinal adenosine A1 receptors failed to reduce increased tonic G-protein signaling in the spinal cord after nerve injury. These data support a role for chronic adenosine A1 receptor stimulation after nerve injury to result in hypersensitivity.
authors.affiliation: Department of Anesthesiology and Physiology/Pharmacology and the Center for the Study of Pharmacologic Plasticity in the Presence of Pain, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Martin
authors.forename: James C
authors.initials: JC
authors.lastname: Eisenach
authors.forename: Jaime
authors.initials: J
authors.lastname: Misler
authors.forename: Steven R
authors.initials: SR
authors.lastname: Childers
mesh_terms: D000241:Adenosine / Q000009:adverse effects; D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D004334:Drug Administration Schedule; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D010812:Physical Stimulation / Q000379:methods; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D012684:Sensory Thresholds / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013118:Spinal Cord Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D013460:Sulfur Isotopes / Q000493:pharmacokinetics; D013806:Theophylline / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D013460:Sulfur Isotopes; C053907:8-cyclopentyl-1,3-dimethylxanthine; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D013806:Theophylline; D000241:Adenosine