BACKGROUND: Painful peripheral nerve injury results in disordered sensory neuron function that contributes to the pathogenesis of neuropathic pain. However, the relative roles of neurons with transected axons versus intact adjacent neurons have not been resolved. An essential first step is identification of electrophysiologic changes in these two neuronal populations after partial nerve damage. METHODS: Twenty days after spinal nerve ligation (SNL), intracellular recordings were obtained from axotomized fifth lumbar (L5) dorsal root ganglion neurons and adjacent, intact L4 neurons, as well as from control neurons and others subjected to sham-SNL surgery. RESULTS: Pronounced electrophysiologic changes were seen only in L5 neurons after SNL. Both Aalpha/beta and Adelta neuron types showed increased action potential duration, decreased afterhyperpolarization amplitude and duration, and decreased current threshold for action potential initiation. Aalpha/beta neurons showed resting membrane potential depolarization, and increased repetitive firing during sustained depolarization developed in Adelta neurons. The afterhyperpolarization duration in neurons with C fibers shortened after axotomy. In contrast to the axotomized L5 neurons, neighboring L4 neurons showed no changes in action potential duration, afterhyperpolarization dimensions, or excitability after SNL. Depolarization rate (dV/dt) increased after SNL in L4 Aalpha/beta and Adelta neurons but decreased in L5 neurons. Time-dependent rectification during hyperpolarizing current injection (sag) was greater after SNL in Aalpha/beta L4 neurons compared with L5. Sham-SNL surgery produced only a decreased input resistance in Aalpha/beta neurons and a decreased conduction velocity in medium-sized cells. In the L5 ganglion after axotomy, a novel set of neurons, consisting of 24% of the myelinated population, exhibited long action potential durations despite myelinated neuron conduction velocities, particularly depolarized resting membrane potential, low depolarization rate, and absence of sag. CONCLUSIONS: These findings indicate that nerve injury-induced electrical instability is restricted to axotomized neurons and is absent in adjacent intact neurons.
BACKGROUND: Painful peripheral nerve injury results in disordered sensory neuron function that contributes to the pathogenesis of neuropathic pain. However, the relative roles of neurons with transected axons versus intact adjacent neurons have not been resolved. An essential first step is identification of electrophysiologic changes in these two neuronal populations after partial nerve damage. METHODS: Twenty days after spinal nerve ligation (SNL), intracellular recordings were obtained from axotomized fifth lumbar (L5) dorsal root ganglion neurons and adjacent, intact L4 neurons, as well as from control neurons and others subjected to sham-SNL surgery. RESULTS: Pronounced electrophysiologic changes were seen only in L5 neurons after SNL. Both Aalpha/beta and Adelta neuron types showed increased action potential duration, decreased afterhyperpolarization amplitude and duration, and decreased current threshold for action potential initiation. Aalpha/beta neurons showed resting membrane potential depolarization, and increased repetitive firing during sustained depolarization developed in Adelta neurons. The afterhyperpolarization duration in neurons with C fibers shortened after axotomy. In contrast to the axotomized L5 neurons, neighboring L4 neurons showed no changes in action potential duration, afterhyperpolarization dimensions, or excitability after SNL. Depolarization rate (dV/dt) increased after SNL in L4 Aalpha/beta and Adelta neurons but decreased in L5 neurons. Time-dependent rectification during hyperpolarizing current injection (sag) was greater after SNL in Aalpha/beta L4 neurons compared with L5. Sham-SNL surgery produced only a decreased input resistance in Aalpha/beta neurons and a decreased conduction velocity in medium-sized cells. In the L5 ganglion after axotomy, a novel set of neurons, consisting of 24% of the myelinated population, exhibited long action potential durations despite myelinated neuron conduction velocities, particularly depolarized resting membrane potential, low depolarization rate, and absence of sag. CONCLUSIONS: These findings indicate that nerve injury-induced electrical instability is restricted to axotomized neurons and is absent in adjacent intact neurons.
Authors: Geza Gemes; Marcel Rigaud; Paul D Weyker; Stephen E Abram; Dorothee Weihrauch; Mark Poroli; Vasiliki Zoga; Quinn H Hogan Journal: Anesthesiology Date: 2009-08 Impact factor: 7.892