title: Release of gamma-aminobutyric acid in the dorsal horn and suppression of tactile allodynia by spinal cord stimulation in mononeuropathic rats.
abstract: OBJECTIVE
  The aim of the present study is to monitor the extracellular gamma-aminobutyric acid (GABA) levels in the lumbar dorsal horn of allodynic rats, which respond to spinal cord stimulation (SCS) with a normalization of the tactile withdrawal threshold. In addition, we monitored the GABA levels in nonresponding and sham-stimulated rats.
  
  
  METHODS
  Partial constriction injury of the sciatic nerve was performed, and a permanent electrode for SCS was inserted into the spinal canal. The response to SCS was assessed with von Frey hairs in awake animals. Later, microdialysis was performed in the dorsal horn of the spinal cord under halothane anesthesia. The concentration of GABA in the microdialysate was assessed by high-performance liquid chromatography.
  
  
  RESULTS
  Extracellular GABA levels in rats with sciatic nerve lesions and allodynia (2.3 +/- 0.5 nmol/L) were significantly lower (P < 0.001) than in control rats with intact sciatic nerves (8.1 +/- 1.0 nmol/L), whereas only slightly decreased GABA levels (5.7 +/- 1.1 nmol/L) were detected in nonallodynic rats with sciatic nerve lesions. In the allodynic rats, which respond to SCS by a normalization of the tactile withdrawal threshold, significantly (P < 0.001) increased GABA levels (6.7 +/- 2.3 nmol/L) were detected after SCS. In contrast, neither the allodynic rats, which did not respond to SCS, nor the sham-stimulated allodynic rats displayed increased GABA levels in response to stimulation.
  
  
  CONCLUSIONS
  Our results indicate that the development of allodynia, a common symptom in neuropathic pain states, may be linked to a decreased spinal release of GABA. We suggest that an SCS-induced release of GABA could be important for the suppression of allodynia observed in rats after SCS. Similar mechanisms could also be involved in the SCS-induced alleviation of pain in patients with peripheral neuropathy.
authors.affiliation: Department of Neurosurgery, Karolinska Hospital, Karolinska Institute Center for Pain Research, Stockholm, Sweden.
authors.forename: C O
authors.initials: CO
authors.lastname: Stiller
authors.forename: J G
authors.initials: JG
authors.lastname: Cui
authors.forename: W T
authors.initials: WT
authors.lastname: O'Connor
authors.forename: E
authors.initials: E
authors.lastname: Brodin
authors.forename: B A
authors.initials: BA
authors.lastname: Meyerson
authors.forename: B
authors.initials: B
authors.lastname: Linderoth
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004599:Electric Stimulation Therapy / Q000295:instrumentation; D004567:Electrodes, Implanted; D005727:Ganglia, Spinal / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D017551:Microdialysis; D009437:Neuralgia / Q000473:pathology / Q000503:physiopathology*; D017288:Pain Threshold / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D012684:Sensory Thresholds / Q000502:physiology; D014110:Touch / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid