Related Experiment Video
Updated: May 13, 2026
Use of In Vivo Single-fiber Recording and Intact Dorsal Root Ganglion with Attached Sciatic Nerve to Examine the Mechanism of Conduction Failure
Published on: August 27, 2019
Axotomy-induced changes in activity-dependent slowing in peripheral nerve fibres: role of
I Mazo1, I Rivera-Arconada, C Roza
1Dpto. Fisiología, Edificio de Medicina Universidad de Alcalá, Madrid, Spain.
Background:
Slowing refers to the gradual decrease in conduction velocity evoked by repetitive electrical stimuli. The underlying mechanisms are still poorly understood, and its physiological/pathological relevance scarcely discussed; however, changes in axonal conduction properties might unmask abnormal nociceptor function and alter the encoding time window at the spinal cord.
Methods:
Here, we characterized and compared the slowing in isolated units recorded from intact and axotomized saphenous nerves from mice, in vitro. We evaluated the role of hyperpolarization-activated/HCN channel current, Ih , in the generation of slowing, by examining the effect of the specific Ih blocker ZD7288.
Results:
Based on their degree of slowing, intact C-fibres were classified as presumed nociceptors or non-nociceptors (>13% or <7% latency increase, respectively). Upon ZD7288 treatment, slowing was significantly augmented in 19/25 of the presumed C-nociceptors. In nerve-end neuromas, axotomized C-fibres could not be classified by their degree of slowing, which, in addition, was unrelated to the presence of ectopic mechanosensitivity. Axotomized fibres showed a ∼2.5-fold reduction in their slowing as compared with intact units and the effects of ZD7288 were more prominent, both in magnitude and percentage of sensitive fibres. Interestingly, in control conditions, all fibres sensitive to ZD7288 were more resistant to slowing.
Conclusions:
Under our experimental conditions, slowing seems largely dependent on functional Ih . The marked decrease in slowing after axotomy in C-fibres fits with the increased expression of functional hyperpolarization-activated/HCN channel current and may underlie the analgesic effects of the specific Ih blocker ZD7288 previously described in neuropathic pain models.
Related Concept Videos
01:41Action Potentials
01:24Local Anesthetics: Differential Sensitivity of Nerve Fibers
01:14Action Potential
Membrane potential in neurons
Neurons typically have a resting membrane potential of about -70 millivolts (mV). When they receive...
01:14Action Potential
Membrane potential in neurons
Neurons typically have a resting membrane potential of about -70 millivolts (mV). When they receive...
01:28Action Potential: Phases of Stimulation
Resting Phase:
In this phase, the cell's membrane is at its resting potential, typically around -70 millivolts (mV) for neurons. Inside the cell, there is a higher concentration of potassium ions (K+) and a lower concentration of sodium ions (Na+). Voltage-gated sodium channels are closed, and...
01:19The Role of Ion Channels in Neuronal Computation
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential.