Analysis of spontaneous activity of superficial dorsal horn neurons in vitro: neuropathy-induced changes.

Abstract

The superficial dorsal horn contains large numbers of interneurons which process afferent and descending information to generate the spinal nociceptive message. Here, we set out to evaluate whether adjustments in patterns and/or temporal correlation of spontaneous discharges of these neurons are involved in the generation of central sensitization caused by peripheral nerve damage. Multielectrode arrays were used to record from discrete groups of such neurons in slices from control or nerve damaged mice. Whole-cell recordings of individual neurons were also obtained. A large proportion of neurons recorded extracellularly showed well-defined patterns of spontaneous firing. Clock-like neurons (CL) showed regular discharges at ∼6Hz and represented 9% of the sample in control animals. They showed a tonic-firing pattern to direct current injection and depolarized membrane potentials. Irregular fast-burst neurons (IFB) produced short-lasting high-frequency bursts (2-5 spikes at ∼100Hz) at irregular intervals and represented 25% of the sample. They showed bursting behavior upon direct current injection. Of the pairs of neurons recorded, 10% showed correlated firing. Correlated pairs always included an IFB neuron. After nerve damage, the mean spontaneous firing frequency was unchanged, but the proportion of CL increased significantly (18%) and many of these neurons appeared to acquire a novel low-threshold A-fiber input. Similarly, the percentage of IFB neurons was unaltered, but synchronous firing was increased to 22% of the pairs studied. These changes may contribute to transform spinal processing of nociceptive inputs following peripheral nerve damage. The specific roles that these neurons may play are discussed.