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Modulation of Spinal GABAergic Inhibition and Mechanical Hypersensitivity following Chronic Compression of Dorsal Root Ganglion in the Rat

 Moon Chul Lee  ;  Taick Sang Nam  ;  Se Jung Jung  ;  Young S. Gwak  ;  JoongWoo Leem 
 NEURAL PLASTICITY, Vol.2015 : 924728, 2015 
Journal Title
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Animals ; Behavior, Animal/drug effects ; Benzylamines/therapeutic use ; Bicuculline/therapeutic use ; GABA Antagonists/therapeutic use* ; GABA-A Receptor Antagonists/therapeutic use ; GABA-B Receptor Antagonists/therapeutic use ; Ganglia, Spinal/physiopathology* ; Hindlimb/innervation ; Hindlimb/pathology ; Hyperalgesia/drug therapy* ; Hyperalgesia/etiology ; Hyperalgesia/physiopathology ; Male ; Pain Measurement/drug effects ; Phosphinic Acids/therapeutic use ; Rats ; Rats, Sprague-Dawley ; Spinal Cord/physiopathology* ; Spinal Cord Compression/drug therapy* ; Spinal Cord Compression/etiology ; Spinal Cord Compression/physiopathology ; gamma-Aminobutyric Acid/metabolism
Chronic compression of dorsal root ganglion (CCD) results in neuropathic pain. We investigated the role of spinal GABA in CCD-induced pain using rats with unilateral CCD. A stereological analysis revealed that the proportion of GABA-immunoreactive neurons to total neurons at L4/5 laminae I-III on the injured side decreased in the early phase of CCD (post-CCD week 1) and then returned to the sham-control level in the late phase (post-CCD week 18). In the early phase, the rats showed an increase in both mechanical sensitivity of the hind paw and spinal WDR neuronal excitability on the injured side, and such increase was suppressed by spinally applied muscimol (GABA-A agonist, 5 nmol) and baclofen (GABA-B agonist, 25 nmol), indicating the reduced spinal GABAergic inhibition involved. In the late phase, the CCD-induced increase in mechanical sensitivity and neuronal excitability returned to pre-CCD levels, and such recovered responses were enhanced by spinally applied bicuculline (GABA-A antagonist, 15 nmol) and CGP52432 (GABA-B antagonist, 15 nmol), indicating the regained spinal GABAergic inhibition involved. In conclusion, the alteration of spinal GABAergic inhibition following CCD and leading to a gradual reduction over time of CCD-induced mechanical hypersensitivity is most likely due to changes in GABA content in spinal GABA neurons.
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1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
Leem, Joong Woo(임중우) ORCID logo https://orcid.org/0000-0002-1605-2230
Jung, Se Jung(정세정)
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