Abstract
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.
Highlights
The activation threshold for A-fiber responses was shifted after nerve injury, when A and A␦ fibers were fully activated (100 A, 0.05 msec), EPSC amplitudes were similar in all four populations (Table 1)
In contrast to excitatory transmission that remains intact after nerve injury, the proportion of superficial dorsal horn neurons with primary afferent-evoked IPSCs was significantly decreased by 17% after constriction injury (CCI) and by 28% after spared nerve injury (SNI) (Fig. 1 A)
The IPSCs remaining in CCI and SNI animals were significantly reduced in both amplitude and duration (Fig. 1 B–D, Table 2)
Summary
Dorsal root potentials and primary afferent depolarization, indicators of presynaptic inhibition at the central terminals of low-threshold myelinated fibers, are diminished after complete sciatic nerve axotomy (Wall and Devor, 1981). Large A-fiber-mediated inhibition of C-fiber-evoked responses in dorsal horn neurons is diminished (Woolf and Wall, 1982). The primary afferent-evoked currents in lamina II neurons were recorded in slices from naive rats and after three types of peripheral nerve injury, complete sciatic nerve transection (SNT), CCI (Bennett and Xie, 1988), and spared nerve injury (SNI) (Decosterd and Woolf, 2000). Excitatory transmission remained intact in all three models, GABAergic inhibition was markedly reduced in the two partial peripheral nerve injury models, CCI and SNI
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