title: Excitability of Aβ sensory neurons is altered in an animal model of peripheral neuropathy.
abstract: BACKGROUND
  Causes of neuropathic pain following nerve injury remain unclear, limiting the development of mechanism-based therapeutic approaches. Animal models have provided some directions, but little is known about the specific sensory neurons that undergo changes in such a way as to induce and maintain activation of sensory pain pathways. Our previous studies implicated changes in the Aβ, normally non-nociceptive neurons in activating spinal nociceptive neurons in a cuff-induced animal model of neuropathic pain and the present study was directed specifically at determining any change in excitability of these neurons. Thus, the present study aimed at recording intracellularly from Aβ-fiber dorsal root ganglion (DRG) neurons and determining excitability of the peripheral receptive field, of the cell body and of the dorsal roots.
  
  
  METHODS
  A peripheral neuropathy was induced in Sprague Dawley rats by inserting two thin polyethylene cuffs around the right sciatic nerve. All animals were confirmed to exhibit tactile hypersensitivity to von Frey filaments three weeks later, before the acute electrophysiological experiments. Under stable intracellular recording conditions neurons were classified functionally on the basis of their response to natural activation of their peripheral receptive field. In addition, conduction velocity of the dorsal roots, configuration of the action potential and rate of adaptation to stimulation were also criteria for classification. Excitability was measured as the threshold to activation of the peripheral receptive field, the response to intracellular injection of depolarizing current into the soma and the response to electrical stimulation of the dorsal roots.
  
  
  RESULTS
  In control animals mechanical thresholds of all neurons were within normal ranges. Aβ DRG neurons in neuropathic rats demonstrated a mean mechanical threshold to receptive field stimulation that were significantly lower than in control rats, a prolonged discharge following this stimulation, a decreased activation threshold and a greater response to depolarizing current injection into the soma, as well as a longer refractory interval and delayed response to paired pulse electrical stimulation of the dorsal roots.
  
  
  CONCLUSIONS
  The present study has demonstrated changes in functionally classified Aβ low threshold and high threshold DRG neurons in a nerve intact animal model of peripheral neuropathy that demonstrates nociceptive responses to normally innocuous cutaneous stimuli, much the same as is observed in humans with neuropathic pain. We demonstrate further that the peripheral receptive fields of these neurons are more excitable, as are the somata. However, the dorsal roots exhibit a decrease in excitability. Thus, if these neurons participate in neuropathic pain this differential change in excitability may have implications in the peripheral drive that induces central sensitization, at least in animal models of peripheral neuropathic pain, and Aβ sensory neurons may thus contribute to allodynia and spontaneous pain following peripheral nerve injury in humans.
authors.affiliation: Farncombe Family Digestive Health Research Institute, McMaster University, 1280 Main St. West, HSC 3N5C, Hamilton, Ontario, Canada.
authors.forename: Yong Fang
authors.initials: YF
authors.lastname: Zhu
authors.forename: James L
authors.initials: JL
authors.lastname: Henry
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D019771:Axotomy; D001703:Biophysics; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005727:Ganglia, Spinal / Q000473:pathology*; D006930:Hyperalgesia / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012585:Sciatica / Q000473:pathology* / Q000503:physiopathology*; D011984:Sensory Receptor Cells / Q000502:physiology*