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The Journal of Neuroscience, August 1, 2002, 22(15):6724-6731
Partial Peripheral Nerve Injury Promotes a Selective Loss of
GABAergic Inhibition in the Superficial Dorsal Horn of the Spinal
Cord
Kimberly A.
Moore*,
Tatsuro
Kohno*,
Laurie A.
Karchewski,
Joachim
Scholz,
Hiroshi
Baba, and
Clifford J.
Woolf
Neural Plasticity Research Group, Department of Anesthesia and
Critical Care, Massachusetts General Hospital and Harvard Medical
School, Charlestown, Massachusetts 02129
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 GABAA
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.
Key words:
neuropathic pain; GAD; CCI; SNI; cell death; disinhibition
*
K.A.M. and T.K. contributed equally to this work.
Copyright © 2002 Society for Neuroscience 0270-6474/02/22156724-08$05.00/0
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