Conflict of Interest: Bengt Linderoth has a temporary consultant assignment with Medtronic Inc., as well as research support from Medtronic Inc. He also has been consultant to Elekta AB. Otherwise, there is no conflict of interest for any of the authors.
Spinal GABAergic Mechanisms in the Effects of Spinal Cord Stimulation in a Rodent Model of Neuropathic Pain: Is GABA Synthesis Involved?
Article first published online: 14 DEC 2012
© 2012 International Neuromodulation Society
Neuromodulation: Technology at the Neural Interface
Volume 16, Issue 2, pages 114–120, March/April 2013
How to Cite
2012. Spinal GABAergic Mechanisms in the Effects of Spinal Cord Stimulation in a Rodent Model of Neuropathic Pain: Is GABA Synthesis Involved? Neuromodulation 2012; e-pub ahead of print. DOI: 10.1111/ner.12007, , , ,
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
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Source(s) of financial support: The GAD study was supported by grants from Karolinska Institutet. Several of the studies referred to in this article also have been supported by Medtronic Inc.
- Issue published online: 1 APR 2013
- Article first published online: 14 DEC 2012
- Manuscript Accepted: 25 OCT 2012
- Manuscript Revised: 9 OCT 2012
- Manuscript Received: 8 MAY 2012
- Karolinska Institutet
- Karolinska Institutet and from Medtronic Inc
- neuropathic pain;
- spinal cord stimulation
The effects of spinal cord stimulation (SCS) on the spinal γ-amino butyric acid (GABA) system have previously been studied in animal models of neuropathic pain. These studies, confirming the pivotal role of segmental GABA actions for the efficacy of SCS, have led to the question if the disturbance of the GABA inhibitory system as demonstrated both in basal and clinical studies also encompasses malfunction of the GABA synthesis.
Rat models of neuropathic pain were submitted to SCS applied with “clinical SCS parameters.” The levels of the GABA-synthesizing enzymes, glutamic acid decarboxylase (GAD) 65 and GAD 67, in the spinal dorsal horns (DHs) were analyzed using Western blot and immunohistochemistry comparing responders and nonresponders to SCS, with and without SCS, as well as controls.
There were no significant differences in general DH GAD levels between hypersensitive, nonhypersensitive, and intact control animals. Although SCS did not significantly influence these levels, there was a significant local augmentation of GAD 65 expression in lamina II in SCS responders subjected to SCS immediately prior to tissue collection as compared with SCS nonresponders.
Although GABAergic mechanisms are closely related to the effects of SCS, the presence of neuropathic signs and their suppression by SCS are not associated with changes of the general levels of the spinal DH GABA-synthesizing enzymes. However, in SCS responding animals, there was a significant increased expression of GAD 65 in lamina II, presumably reflecting an augmented GABA synthesis following SCS.