title: Suppressed GABAergic signaling in the zona incerta causes neuropathic pain in a thoracic hemisection spinal cord injury rat model.
abstract: OBJECTIVE
  Suppression of the gamma-aminobutyric acid (GABA)ergic activity of the zona incerta (ZI) reportedly plays a role in neuropathic pain after spinal cord injury (SCI). A reduction in GABAergic signaling in the ZI of a thoracic hemisection-SCI rat model has been suggested, but not clearly demonstrated. Accordingly, our objective was to investigate whether GABAergic signals influence SCI-induced neuropathic pain.
  
  
  METHODS
  In vivo, we recorded and compared single-unit, neuronal activity between hemisection-SCI and sham-operated rat models. Furthermore, we analyzed neuronal activity in both models following treatment with either a GABAA receptor agonist (muscimol) or antagonist (bicuculline).
  
  
  RESULTS
  Rats that underwent hemisection SCI exhibited reduced hindpaw withdrawal thresholds, latencies, and decreased ZI neuronal activity compared with sham-operated controls. Importantly, muscimol treatment increased, whereas bicuculline decreased, the firing rates of the ZI neurons. The muscimol treated, hemisection-SCI rats also exhibited increased hindpaw withdrawal thresholds and latencies.
  
  
  CONCLUSIONS
  These data provide evidence that neuropathic pain after SCI is caused by decreased GABAergic signaling in the ZI. Furthermore, our data demonstrate that infusion of a GABAergic drug into the ZI could restore its inhibitory action and improve neuropathic pain behaviors.
authors: Department of Medical Neuroscience and Neurosurgery, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea.
authors: Hyeong Cheol
authors: HC
authors: Moon
authors: Department of Radiology, Daejeon St. Mary's Hospital, The Catholic University of Korea, Republic of Korea.
authors: Youn Joo
authors: YJ
authors: Lee
authors: Department of Neurosurgery, Saint Vincent's Hospital, The Catholic University of Korea, Republic of Korea.
authors: Chul Bum
authors: CB
authors: Cho
authors: Department of Neurosurgery, Chungbuk National University Hospital, Chungbuk National University, College of Medicine, Cheongju, Republic of Korea. Electronic address: youngseokparkmd@gmail.com.
authors: Young Seok
authors: YS
authors: Park
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D018755:GABA Agonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology*; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009437:Neuralgia / Q000209:etiology* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000150:complications* / Q000378:metabolism; D065820:Zona Incerta / Q000187:drug effects* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018755:GABA Agonists; D058787:GABA-A Receptor Antagonists; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline
keywords: GABA; Neural cell recording; Neuropathic pain; Spinal cord injury; Zona incerta