CELL-TYPE-SPECIFIC CHANGES OF THE MEMBRANE-PROPERTIES OF PERIPHERALLY-AXOTOMIZED DORSAL-ROOT GANGLION NEURONS IN A RAT MODEL OF NEUROPATHICPAIN

Recent evidence indicates that neuropathic pain from partial periphera l nerve injury is maintained by electrophysiologically abnormal signal s from injured sensory neurons. To gain an insight into the mechanisms underlying this electrophysiological abnormality, we examined the eff ects of S-1 spinal nerve transection on the membrane properties of S-1 dorsal root ganglion neurons one to two weeks after injury. This inju ry produced significant action potential broadening [40% (1 ms) in C-, 149% (1.5 ms) in A delta- and 84% (0.5 ms) in A alpha/beta-cells], wh ich was primarily due to the enhancement of the ''shoulder'' appearing on the falling phase of the action potential in C-and AG-cells and th e emergence of a shoulder in A alpha/beta-cells, and significant cell- type specific changes in the time-course of the rising phase of the ac tion potential; i.e. an increase in rise time (A delta: 35%, 0.15 ms; A alpha/beta: 13%, 0.04 ms) and a decrease in the maximal rate of rise (A delta: 17%, 77 V/s; A alpha/beta: 13%, 79 V/s). In addition, the n erve injury led to a significant reduction of the rheobase, an index o f neuronal excitability, in all types of cells (by 41% in C-, 71% in A delta- and 59% in A alpha/beta-cells). The reduction of rheobase in A -cells was associated with a concomitant increase in apparent input re sistance (by 269% in A delta- and 192% in A alpha/beta-cells), which w as measured near the resting membrane potential. By contrast, the rheo base reduction in C-cells was associated with a concurrent depolarizin g shift (similar to 4 mV) of the resting membrane potential. The nerve injury-induced reduction of rheobase was not accompanied by related c hange in input resistance or threshold potential in any of the cell po pulations. The present results indicate that chronic peripheral axotom y of dorsal root ganglion neurons, which gives rise to neuropathic pai n, produces profound changes in the action potential waveform of dorsa l root ganglion neurons in a cell type-specific fashion. Furthermore, the results suggest that the axotomy increases the excitability of dor sal root ganglion neurons not by altering input resistance (i.e. leak conductance) or threshold potential, but by increasing apparent input resistance near the resting membrane potential in A-cells and decreasi ng the resting membrane potential in C-cells. (C) 1998 IBRO. Published by Elsevier Science Ltd.