Effects of spinal cord stimulation on touch-evoked allodynia involve GABAergic mechanisms. An experimental study in the mononeuropathic rat.
There is much evidence that tactile allodynia in rat models of mononeuropathy produced by sciatic nerve constriction is linked to disturbance of spinal GABAergic functions. Spinal cord stimulation (SCS) applied to such animals via chronically implanted electrodes may in some of the animals induce a significant increase of the withdrawal threshold in response to innocuous mechanical stimulation with von Frey filaments applied to the paw of the nerve ligated leg. The present study was performed in mononeuropathic animals with definite signs of tactile allodynia, which did not respond to SCS, GABA and the GABAB-agonist baclofen were administered intrathecally, in doses per se insufficient to influence the withdrawal thresholds, together with the previously ineffective SCS. This combination resulted in a marked and long-lasting increase of the thresholds. The GABAA-agonist muscimol given together with SCS also produced a similar, but less prominent threshold increase. The GABAB-antagonist 5-aminovaleric acid (5-AVA) produced a transient suppression of the threshold increase induced by SCS together with either GABA or baclofen. In contrast, the GABAA-antagonist bicuculline had no apparent inhibitory effect on the threshold augmentation produced by SCS combined with GABA or baclofen. It is concluded that SCS may operate by upgrading the spinal GABAergic systems and that its potential for producing pain relief is dependent upon the availability of responsive GABA-containing inhibitory interneurons. Moreover, it seems that the effects of SCS are more linked to the GABAB-than to the GABAA-receptor system.
Cui
J G
JG
Karolinska Institute Center for Pain Research, Karolinska Hospital, Sweden.
Linderoth
B
B
Meyerson
B A
BA
D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000627:therapeutic use; D004558:Electric Stimulation; D018755:GABA Agonists / Q000008:administration & dosage / Q000627:therapeutic use; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D007278:Injections, Spinal; D008297:Male; D009118:Muscimol / Q000008:administration & dosage / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000503:physiopathology; D013116:Spinal Cord / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D001418:Baclofen