title: Tactile allodynia in the absence of C-fiber activation: altered firing properties of DRG neurons following spinal nerve injury.
abstract: We examined the relation between ectopic afferent firing and tactile allodynia in the Chung model of neuropathic pain. Transection of the L5 spinal nerve in rats triggered a sharp, four- to six-fold increase in the spontaneous ectopic discharge recorded in vivo in sensory axons in the ipsilateral L5 dorsal root (DR). The increase, which was not yet apparent 16 h postoperatively, was complete by 24 h. This indicates rapid modification of the electrical properties of the neurons. Only A-neurons, primarily rapidly conducting A-neurons, contributed to the discharge. No spontaneously active C-neurons were encountered. Tactile allodynia in hindlimb skin emerged during precisely the same time window after spinal nerve section as the ectopia, suggesting that ectopic activity in injured myelinated afferents can trigger central sensitization, the mechanism believed to be responsible for tactile allodynia in the Chung model. Most of the spike activity originated in the somata of axotomized DRG neurons; the spinal nerve end neuroma accounted for only a quarter of the overall ectopic barrage. Intracellular recordings from afferent neuron somata in excised DRGs in vitro revealed changes in excitability that closely paralleled those seen in the DR axon recordings in vivo. Corresponding changes in biophysical characteristics of the axotomized neurons were catalogued. Axotomy carried out at a distance from the DRG, in the mid-portion of the sciatic nerve, also triggered increased afferent excitability. However, this increase occurred at a later time following axotomy, and the relative contribution of DRG neuronal somata, as opposed to neuroma endings, was smaller. Axotomy triggers a wide variety of changes in the neurochemistry and physiology of primary afferent neurons. Investigators studying 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 population of neurons whose firing properties change suddenly and synchronously following axotomy, and whose activity is associated with tactile allodynia, provides a powerful vehicle for defining the specific cascade of cellular and molecular events that underlie neuropathic pain.
authors.affiliation: Department of Cell and Animal Biology, Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91904, Israel Department of Physiology, Medical School, St. Thomas', London, UK Physiologisches Institut, Christian-Albrechts Universitat, 24098 Kiel, Germany.
authors.forename: Chang-Ning
authors.initials: CN
authors.lastname: Liu
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Wall
authors.forename: Efrat
authors.initials: E
authors.lastname: Ben-Dor
authors.forename: Martin
authors.initials: M
authors.lastname: Michaelis
authors.forename: Ron
authors.initials: R
authors.lastname: Amir
authors.forename: Marshall
authors.initials: M
authors.lastname: Devor
mesh_terms: D000818:Animals; D019771:Axotomy; D001522:Behavior, Animal / Q000502:physiology; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000473:pathology / Q000502:physiology*; D008297:Male; D009409:Nerve Crush; D009412:Nerve Fibers / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010146:Pain / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D013127:Spinal Nerves / Q000293:injuries*; D013997:Time Factors