L5 Spinal Nerve Axotomy Induces Distinct Electrophysiological Changes in Axotomized L5- and Adjacent L4-Dorsal Root Ganglion Neurons in Rats <i>In Vivo</i>

Peripheral neuropathic pain (PNP) is a major health problem for which effective drug treatment lacking. Its underlying neuronal mechanisms are still illusive, but pre-clinical studies using animal models of PNP including the L5-spinal nerve axotomy (L5-SNA) model, suggest that it partly caused by excitability changes in dorsal root ganglion (DRG) neurons. L5-SNA results two DRG groups: (1) axotomized/damaged neurons L5- plus some L4-DRGs, and (2) ipsilateral L4-neurons with intact/uninjured fibers intermingling degenerating L5-fibers. The axotomized deprived peripherally derived trophic factors degenerate causing neuroinflammation, whereas uninjured L4-neuorns subject to increased neuroinflammation associated Wallerian degeneration L5-nerve fibers. Whether these groups exhibit similar or distinct electrophysiological after remains unresolved. Conflicting evidence this may result from assuming all L4-fibers undamaged. Here, we recorded somatic action potentials (APs) intracellularly C- A-fiber L4/L5 vivo, examine our hypothesis would induce populations Consistent hypothesis, found (7 days post-SNA), SNA rats established hypersensitivity, slower AP kinetics L5-neurons faster L4-nociceptive decreased rise time Aδ-and Aβ-fiber nociceptors, after-hyperpolarization duration nociceptors. We also several not neurons, L5-neurons. (decreased refractory period) consistent their reported hyperexcitability lead repetitive firing thus provide enhanced afferent input necessary initiating and/or maintaining development. contribute central via neurotransmitter release nervous system (CNS).