Axotomy- and autotomy-induced changes in the excitability of rat dorsal root ganglion neurons

The spontaneous, ectopic activity in sensory nerves that is induced by peri pheral nerve injury is thought to contribute to the generation of "neuropat hic" pain in humans. To examine the cellular mechanisms that underlie this activity, neurons in rat L-4-L-5 dorsal root ganglion (DRG) were first grou ped as "large," "medium," or "small" on the basis of their size (input capa citance) and action potential (AP) shape. A fourth group of cells that exhi bited a pronounced afterdepolarization (ADP) were defined as AD-cells. Whol e cell recording was used to compare the properties of control neurons with those dissociated from rats in which the sciatic nerve had been sectioned ("axotomy" group) and with neurons from rats that exhibited self-mutilatory behavior in response to sciatic nerve section ("autotomy" group). Increase s in excitability in all types of DRG neuron were seen within 2-7 wk of axo tomy. Resting membrane potential (RMP) and the amplitude and duration of th e afterhyperpolarization (AHP) that followed the AP were unaffected. Effect s of axotomy were greatest in the small, putative nociceptive cells and lea st in the large cells. Moderate changes were seen in the medium and AD-cell s. Compared to control neurons, axotomized neurons exhibited a higher frequ ency of evoked AP discharge in response to 500-ms depolarizing current inje ctions; i.e., "gain" was increased and accommodation was decreased. The min imum current required to discharge an AP (rheobase) was reduced. There were significant increases in spike width in small cells and significant increa ses in spike height in small, medium, and AD-cells. The electrophysiologica l changes promoted by axotomy were intensified in animals that exhibited au totomy; spike height, and spike width were significantly greater than contr ol for all cell types. Under our experimental conditions, spontaneous activ ity was never encountered in neurons dissociated from animals that exhibite d autotomy. Thus changes in the electrical properties of cell bodies alone may not entirely account for injury-induced spontaneous activity in sensory nerves. The onset of autotomy coincided with alterations in the excitabili ty of large, putative nonnociceptive, neurons. Thus large cells from the au totomy group were much more excitable than those from the axotomy group, wh ereas small cells from the autotomy group were only slightly more excitable . This is consistent with the hypothesis that the onset of autotomy is asso ciated with changes in the properties of myelinated fibers. Changes in Ca2 and K+ channel conductances that contribute to axotomy- and autotomy-induc ed changes in excitability are addressed in the accompanying paper.