Tactile allodynia in the absence of C-fiber activation: altered firing properties of DRG neurons following spinal nerve injury

We examined the relation between ectopic afferent firing and tactile allody nia in the Chung model of neuropathic pain. Transection of the L5 spinal ne rve in rats triggered a sharp, four- to six-fold increase in the spontaneou s ectopic discharge recorded in vivo in sensory axons in the ipsilateral L5 dorsal root (DR). The increase, which was not yet apparent 16 h postoperat ively, was complete by 24 h. This indicates rapid modification of the elect rical properties of the neurons. Qnly A-neurons, primarily rapidly conducti ng A-neurons, contributed to the discharge. No spontaneously active C-neuro ns were encountered. Tactile allodynia in hindlimb skin emerged during prec isely the same time window after spinal nerve section as the ectopia, sugge sting that ectopic activity in injured myelinated afferents can trigger cen tral sensitization, the mechanism believed to be responsible for tactile al lodynia in the Chung model. Most of the spike activity originated in the so mata of axotomized DRG neurons; the spinal nerve end neuroma accounted for only a quarter of the overall ectopic barrage. Intracellular recordings fro m afferent neuron somata in excised DRGs in vitro revealed changes in excit ability that closely paralleled those seen in the DR axon recordings in viv o. Corresponding changes in biophysical characteristics of the axotomized n eurons were catalogued. Axotomy carried out at a distance from the DRG, in the mid-portion of the sciatic nerve, also triggered increased afferent exc itability. However, this increase occurred at a later time following axotom y, and the relative contribution of DRG neuronal somata, as opposed to neur oma endings, was smaller. Axotomy triggers a wide variety of changes in the neurochemistry and physiology of primary afferent neurons. Investigators s tudying DRG neurons in culture need to be alert to the rapidity with which axotomy, an inevitable consequence of DRG excision and dissociation, alters key properties of these neurons. Our identification of a specific populati on of neurons whose firing properties change suddenly and synchronously fol lowing axotomy, and whose activity is associated with tactile allodynia, pr ovides a powerful vehicle for defining the specific cascade of cellular and molecular events that underlie neuropathic pain. (C) 2000 International As sociation for the Study of Pain. Published by Elsevier Science B.V. All rig hts reserved.