Effect of spinal cord stimulation on tactile hypersensitivity in mononeuropathic rats is potentiated by simultaneous GABA(B) and adenosine receptor activation.
In rats with abnormally low withdrawal thresholds ('allodynia') in one hindpaw induced by a photochemical sciatic lesion, an intrathecal catheter was inserted to the lumber enlargement and an epidural electrode was implanted at T11. I.t. administration of GABA(B) or adenosine A1 receptor agonists (baclofen, R(-)-N6-(2-phenylisopropyl)adenosine (R-PIA)) suppressed allodynia in a dose-dependent fashion. When the two agonists were given together, each in an ineffective dose, there was a normalization of the thresholds. Rats, in which spinal cord stimulation (SCS) could not suppress the allodynia (non-responders), were transformed into SCS-responders by injection of baclofen and R-PIA in low, ineffective doses, combined with SCS. In SCS responding rats, combination of a selective GABA(B) and an adenosine A1 receptor antagonist (CGP 55845, CPT) in low, ineffective doses abolished the SCS-induced threshold normalization. These results indicate that GABAergic and adenosine-dependent mechanisms are involved in the SCS effect and further suggest a strategy for enhancing the therapeutic efficacy of SCS.
Cui
J G
JG
Department of Neurosurgery, Karolinska Institute Center for Pain Research, Karolinska Institute/Hospital, Stockholm, Sweden.
Meyerson
B A
BA
Sollevi
A
A
Linderoth
B
B
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004558:Electric Stimulation; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D006614:Hindlimb / Q000503:physiopathology; D006941:Hyperesthesia / Q000503:physiopathology*; D008297:Male; D010721:Phosphinic Acids / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology*; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology*; D012584:Sciatic Nerve / Q000293:injuries* / Q000503:physiopathology; D012684:Sensory Thresholds / Q000187:drug effects*; D013116:Spinal Cord / Q000503:physiopathology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D018755:GABA Agonists; D018756:GABA Antagonists; D010721:Phosphinic Acids; D011412:Propanolamines; D018080:Receptors, GABA-B; D018047:Receptors, Purinergic P1; C085075:CGP 55845A; C047235:N-(1-methyl-2-phenylethyl)adenosine; C053907:8-cyclopentyl-1,3-dimethylxanthine; D005680:gamma-Aminobutyric Acid; D013806:Theophylline; D001418:Baclofen; D000241:Adenosine