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1 Department of Pharmacology and Centre for Neuroscience, University of Alberta, Edmonton, Canada
2 School of Medical Sciences, RMIT University, Bundoora, Victoria, Australia
* To whom correspondence should be addressed. E-mail: peter.a.smith{at}ualberta.ca.
Peripheral nerve injury increases spontaneous action potential discharge in spinal dorsal horn neurons and augments their response to peripheral stimulation. This central hypersensitivity, which relates to the onset and persistence of neuropathic pain, reflects spontaneous activity in primary afferent fibers as well as long-term changes in the intrinsic properties of the dorsal horn (centralization). To isolate and investigate cellular mechanisms underlying centralization, sciatic nerves of 20d old rats were subjected to 13-25d of chronic constriction injury (CCI; Mosconi-Kruger polyethylene cuff model). Spinal cord slices were then acutely prepared from sham-operated or CCI-animals and whole-cell recording used to compare the properties of five types of substantia gelatinosa neuron. These were defined as tonic, irregular, phasic, transient or delay according to their discharge pattern in response to depolarizing current. CCI did not affect resting membrane potential, rheobase or input resistance in any neuron type but increased the amplitude and frequency of spontaneous and miniature EPSCs in delay, transient and irregular cells. These changes involved alterations in the action potential-independent neurotransmitter release machinery and possible increases in the postsynaptic effectiveness of glutamate. By contrast, in tonic cells, CCI reduced the amplitude and frequency of spontaneous and miniature EPSCs. Such changes may relate to the putative role of tonic cells as inhibitory GABAergic interneurons whereas increased synaptic drive to delay cells may relate to their putative role as the excitatory output neurons of the substantia gelatinosa. Complementary changes in synaptic excitation of inhibitory and excitatory neurons may thus contribute to pain centralization.
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