title: Spinal GABAergic mechanisms in the effects of spinal cord stimulation in a rodent model of neuropathic pain: is GABA synthesis involved?
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Camilla
authors.initials: C
authors.lastname: Ultenius
authors.forename: Zhiyang
authors.initials: Z
authors.lastname: Song
authors.forename: Paoyan
authors.initials: P
authors.lastname: Lin
authors.forename: Björn A
authors.initials: BA
authors.lastname: Meyerson
authors.forename: Bengt
authors.initials: B
authors.lastname: Linderoth
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D059330:GABAergic Neurons / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006930:Hyperalgesia / Q000503:physiopathology / Q000628:therapy; D008297:Male; D009437:Neuralgia / Q000628:therapy*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000166:cytology / Q000201:enzymology*; D062187:Spinal Cord Stimulation; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2