Activity-dependent slowing of conduction velocity provides a method for identifying different functional classes of c-fibre in the rat saphenous nerve

Gee, Michelle; Lynn, Bruce; Cotsell, B.

doi:10.1016/0306-4522(96)00070-x

Cited by 88 publications

(110 citation statements)

References 20 publications

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“…The A␣␤-and A␦-fibers were stimulated at 0.5-1 Hz. The C-fibers were stim-ulated at 0.1 Hz because stimulations of our preparation at higher frequencies of 1, 0.5, and 0.2 Hz evoked responses with latencies progressively increasing with the number of stimulus (Gee et al 1996) …”

Section: Stimulationmentioning

confidence: 99%

“…3B). To account for the temporal dispersion of the C-fiber CAPC, we analyzed changes in its integrated area as a measure of block (Gokin et al 2001;Huang et al 1997). At each TTX concentration, the stimulation with increasing intensity was done and the corresponding maximum response was determined during the offline analysis (Fig.…”

Section: Capc Block By Ttxmentioning

confidence: 99%

“…Many of them convey nociceptive inputs and are involved in the establishment and maintenance of pathophysiological states, including neuropathic pain, caused by abnormal change in the expression of ion channels. A number of studies have shown a pivotal role of voltage-gated Na ϩ channels in both normal nerve conduction (Hille 2001) and development of neuropathic states Devor and Seltzer 1999;Gold et al 2003;Lai et al 2002;Novakovic et al 1998;Zhang et al 1997).…”

Section: Introductionmentioning

confidence: 99%

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Role of TTX-Sensitive and TTX-Resistant Sodium Channels in Aδ- and C-Fiber Conduction and Synaptic Transmission

Pinto

Derkach

Safronov³

2008

Journal of Neurophysiology

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Pinto V, Derkach VA, Safronov BV. Role of TTX-sensitive and TTX-resistant sodium channels in A␦-and C-fiber conduction and synaptic transmission. J Neurophysiol 99: 617-628, 2008. First published December 5, 2007 doi:10.1152/jn.00944.2007. Thin afferent axons conduct nociceptive signals from the periphery to the spinal cord. Their somata express two classes of Na ϩ channels, TTXsensitive (TTX-S) and TTX-resistant (TTX-R), but their relative contribution to axonal conduction and synaptic transmission is not well understood. We studied this contribution by comparing effects of nanomolar TTX concentrations on currents associated with compound action potentials in the peripheral and central branches of A␦-and C-fiber axons as well as on the A␦-and C-fiber-mediated excitatory postsynaptic currents (EPSCs) in spinal dorsal horn neurons of rat. At room temperature, TTX completely blocked A␦-fibers (IC 50 , 5-7 nM) in dorsal roots (central branch) and spinal, sciatic, and sural nerves (peripheral branch). The C-fiber responses were blocked by 85-89% in the peripheral branch and by 65-66% in dorsal roots (IC 50 , 14 -33 nM) with simultaneous threefold reduction in their conduction velocity. At physiological temperature, the degree of TTX block in dorsal roots increased to 93%. The A␦-and C-fiber-mediated EPSCs in dorsal horn neurons were also sensitive to TTX. At room temperature, 30 nM blocked completely A␦-input and 84% of the C-fiber input, which was completely suppressed at 300 nM TTX. We conclude that in mammals, the TTX-S Na ϩ channels dominate conduction in all thin primary afferents. It is the only type of functional Na ϩ channel in A␦-fibers. In C-fibers, the TTX-S Na ϩ channels determine the physiological conduction velocity and control synaptic transmission. TTX-R Na ϩ channels could not provide propagation of full-amplitude spikes able to trigger synaptic release in the spinal cord.

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Section: Stimulationmentioning

confidence: 99%

Section: Capc Block By Ttxmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role of TTX-Sensitive and TTX-Resistant Sodium Channels in Aδ- and C-Fiber Conduction and Synaptic Transmission

Pinto

Derkach

Safronov³

2008

Journal of Neurophysiology

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“…Previous investigators have noted that nociceptive C fibers have significantly greater slowing than cold fibers, mechano-receptors, and sympathetic efferents (Thalhammer et al, 1994;Gee et al, 1996;Serra et al, 1999). All fibers in our study exhibited activity-dependent slowing of conduction.…”

Section: Two Populations Of Fibers Based On Activity-dependent Slowingmentioning

confidence: 96%

“…The bimodal appearance of these histograms is consistent with the presence of two distinct populations. Other investigators have reported that different classes of unmyelinated nerve fibers in the rat exhibit different amounts of activity-dependent slowing; low levels of activity-dependent slowing are associated with sympathetics, mechanoreceptors, and cold fibers, whereas high levels of activity-dependent slowing are associated with nociceptors (Raymond et al, 1990;Gee et al, 1996). Based on these studies, we have used activity-dependent slowing to separate our data into two populations.…”

Section: Activity-dependent Conduction Velocity Changes Reveal Two DImentioning

confidence: 99%

Activity-dependent slowing of conduction velocity in uninjured L4 C fibers increases after an L5 spinal nerve injury in the rat

Shim

Ringkamp

Lambrinos

et al. 2007

Pain

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Growing evidence suggests that uninjured afferents may play an important role in neuropathic pain following nerve injury. The excitability of nociceptive neurons in the L4 spinal nerve appears to be enhanced following an injury to the adjacent L5 spinal nerve. In this study, we investigated whether the action-potential conduction properties of unlesioned, unmyelinated fibers are also altered. A teased-fiber technique was used to record from single C fibers from the L4 spinal nerve of the rat in vitro. Repeated electrical stimulation of the tibial nerve was used to investigate activity-dependent slowing of conduction velocity. Twin pulse stimulation at a 50 ms interpulse interval allowed investigation of supranormal conduction velocity. Blinded experiments were performed 8-10 days after sham surgery and after an L5 spinal nerve ligation (L5 SNL). Activity-dependent slowing revealed two populations of C fibers, a "nociceptor" population with a large degree of activitydependent slowing and a "non-nociceptor" population with a smaller degree of activity-dependent slowing. Both populations showed enhanced activity-dependent slowing of conduction velocity and enhanced supranormal conduction velocities in lesioned animals compared to sham animals. Activity-dependent slowing was also enhanced after an L5 SNL in the mouse. These alterations in conduction velocity may reflect changes in expression of ion channels responsible for the membrane excitability. These data provide additional evidence that a nerve injury leads to persistent alterations in the properties of adjacent uninjured, unmyelinated fibers.

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Identification of mechano‐sensitive C fibre sensitization and contribution to nerve injury‐induced mechanical hyperalgesia

Hulse

2015

European Journal of Pain

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Background: C fibre hyperexcitability is fundamental to chronic pain development in humans and rodents; therefore, peripheral sensory neuronal sensitization plays a role in the development of mechanical hyperalgesia. However, the axonal properties and underlying mechanisms that are associated to these chronic pain states still require investigation. Methods: Teased fibre electrophysiology of the saphenous nerve was used to identify C fibres in na€ ıve and nerve-injured rats. C fibres were identified using electrical stimulation which further provided conduction velocity slowing profiles. From these nerve filaments evoked responses to mechanical stimuli were recorded. Vehicle or galanin were applied directly to the saphenous nerve trunk prior to stimulation. Results: Increased levels of mechanically evoked activity in mechanosensitive C fibres was associated to reduced conduction failure, enhanced conduction velocity latency recovery and reduced conduction velocity slowing. Mechanical hyperalgesia developed in nerve-injured animals in which mechano-sensitive C fibres demonstrated increased mechanically evoked responses and reduced rate of adaptation. Mechano-sensitive C fibres in nerve-injured animals had reduced levels of conduction velocity slowing, enhanced rate of conduction velocity recovery and reduced firing frequency failure versus na€ ıve animals; all hallmarks of enhanced sensory neuronal excitability. Directly applying the antinociceptive agent galanin to the saphenous nerve trunk in naive animals led to increased conduction failure, reduced latency recovery rate and increased levels of conduction velocity slowing. Discussion: Nerve injury-induced enhanced neural responses to mechanical stimulation are associated to defined parameters setout by conduction velocity slowing, mediated via axonal processing. Application of galanin inhibits axonal excitability.

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Activity-dependent slowing of conduction velocity provides a method for identifying different functional classes of c-fibre in the rat saphenous nerve

Cited by 88 publications

References 20 publications

Role of TTX-Sensitive and TTX-Resistant Sodium Channels in Aδ- and C-Fiber Conduction and Synaptic Transmission

Role of TTX-Sensitive and TTX-Resistant Sodium Channels in Aδ- and C-Fiber Conduction and Synaptic Transmission

Activity-dependent slowing of conduction velocity in uninjured L4 C fibers increases after an L5 spinal nerve injury in the rat

Identification of mechano‐sensitive C fibre sensitization and contribution to nerve injury‐induced mechanical hyperalgesia

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