L5 spinal nerve axotomy induces sensitization of cutaneous L4 Aβ-nociceptive dorsal root ganglion neurons in the rat in vivo

Neurosci Lett. 2016 Jun 15:624:72-7. doi: 10.1016/j.neulet.2016.05.008. Epub 2016 May 9.


Partial nerve injury often leads to peripheral neuropathic pain (PNP), a major health problem that lacks effective drug treatment. PNP is characterized by ongoing/spontaneous pain, and hypersensitivity to noxious (hyperalgesia) and innocuous (allodynia) stimuli. Preclinical studies using the L5 spinal nerve ligation/axotomy (SNL/SNA) model of PNP suggest that this type of chronic pain results partly from sensitization of ipsilateral L4C-and Aδ-fiber nociceptive dorsal root ganglion (DRG) neurons, but whether L4 β-nociceptors, which constitute a substantial group of DRG neurons, also become sensitized remains unanswered. To address this issue, intracellular recordings from somata of cutaneous Aβ-nociceptors (classified according to their dorsal root conduction velocities (>6.5m/s), and physiologically based on their responses to noxious (but not innocuous) mechanical stimuli) were made from L4-DRGs in normal (control) rats and in rats seven days after L5 SNA in vivo. Compared with control, cutaneous L4 Aβ-nociceptive DRG neurons in SNA rats (that developed mechanical hypersensitivity) exhibited sensitization indicated by: a) decreased mean mechanical threshold (from 57.8±7.1 to 10.3±1.7mN), b) decreased mean dorsal root electrical threshold (from 11.4±0.7 to 4.3±0.4V), c) increased mean response to a suprathreshold mechanical stimulus (from 18.5±1.8 to 34±3.7spikes/sec) and d) an obvious, but non-significant, increase in the incidence of ongoing/spontaneous activity (from 3% to 18%). These findings suggest that cutaneous L4 Aβ-nociceptors also become sensitized after L5 SNA, and that sensitization of this subclass of A-fiber nociceptors may contribute both directly and indirectly to nerve injury-induced PNP.

Keywords: Myelinated nerve fibers; Neuropathic pai; Nociceptors; Primary sensory neurons; Uninjured neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Axotomy
  • Female
  • Ganglia, Spinal / physiopathology*
  • Lumbosacral Region
  • Nerve Fibers, Myelinated / physiology*
  • Neuralgia / physiopathology*
  • Nociceptors / physiology*
  • Pain Threshold
  • Physical Stimulation
  • Rats
  • Rats, Wistar
  • Spinal Nerves / injuries*