Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord.
To clarify whether inhibitory transmission in the superficial dorsal horn of the spinal cord is reduced after peripheral nerve injury, we have studied synaptic transmission in lamina II neurons of an isolated adult rat spinal cord slice preparation after complete sciatic nerve transection (SNT), chronic constriction injury (CCI), or spared nerve injury (SNI). Fast excitatory transmission remains intact after all three types of nerve injury. In contrast, primary afferent-evoked IPSCs are substantially reduced in incidence, magnitude, and duration after the two partial nerve injuries, CCI and SNI, but not SNT. Pharmacologically isolated GABA(A) receptor-mediated IPSCs are decreased in the two partial nerve injury models compared with naive animals. An analysis of unitary IPSCs suggests that presynaptic GABA release is reduced after CCI and SNI. Partial nerve injury also decreases dorsal horn levels of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD) 65 kDa ipsilateral to the injury and induces neuronal apoptosis, detected by terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining in identified neurons. Both of these mechanisms could reduce presynaptic GABA levels and promote a functional loss of GABAergic transmission in the superficial dorsal horn.
Moore
Kimberly A
KA
Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Kohno
Tatsuro
T
Karchewski
Laurie A
LA
Scholz
Joachim
J
Baba
Hiroshi
H
Woolf
Clifford J
CJ
D000818:Animals; D015153:Blotting, Western; D016923:Cell Death; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D008026:Ligation; D008297:Male; D009433:Neural Inhibition; D009437:Neuralgia / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D010525:Peripheral Nerves / Q000503:physiopathology*; D010523:Peripheral Nervous System Diseases / Q000473:pathology / Q000503:physiopathology*; D020671:Posterior Horn Cells / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D012585:Sciatica / Q000503:physiopathology; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology*; D009435:Synaptic Transmission; D020429:Tibial Neuropathy / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D007527:Isoenzymes; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2