Mechanisms of Differential Nerve Block

Raymond, Scott B.; Gissen, Aaron J.

doi:10.1007/978-3-642-71110-7_4

Cited by 38 publications

(24 citation statements)

References 151 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Inactivated Na + channels cannot contribute to the action potential and are more sensitive to local anesthetics, thus, block of impulse propagation is enhanced. This mechanism may be a possible explanation for the clinically well-known differential block of motor and sensory nerve fibers, the so-called differential nerve block (Raymond and Gissen, 1987).…”

Section: Introductionmentioning

confidence: 93%

“…In our study with amphibian myelinated nerve, flicker K + channels are more frequently found in thin nerve fibers ( < 5 Ixm) which in general conduct pain. Therefore, a specific blockade of these fibers may lead to a predominant block of pain, a so-called differential nerve block (Rosenberg and Heinonen, 1983;Raymond and Gissen, 1987). In fact, bupivacaine and ropivacaine in low concentrations are clinically used for this purpose.…”

Section: A New Mode Of Nerve Blockmentioning

confidence: 99%

See 1 more Smart Citation

Local anesthetics potently block a potential insensitive potassium channel in myelinated nerve.

Bräu

Nau

Hempelmann

et al. 1995

The Journal of General Physiology

View full text Add to dashboard Cite

A B S T R A C T Effects of some local anesthetics were studied in patch clamp experiments on enzymatically demyelinated peripheral amphibian nerve fibers. Micromolar concentrations of external bupivacaine depolarized the excised membrane considerably. The flicker K § channel was found to be the most sensitive ion channel to local anesthetics in this preparation. Half-maximum inhibiting concentrations (IC50) for extracellular application of bupivacaine, ropivacaine, etidocaine, mepivacaine, lidocaine, and QX-314 were 0.21, 4.2, 8.6, 56, 220, and > 10,000 ~M, respectively. The corresponding concentration-effect curves could be fitted under the assumption of a 1:1 reaction. Application from the axoplasmic side resulted in clearly lower potencies with IC5o values of 2.1, 6.6, 16, 300, 1,200, and 1,250 ~M, respectively. The log(IC 50)-values of the local anesthetics linearly depended on the logarithm of their octanol:buffer distribution coefficients with two regression lines for the piperidine derivatives and the standard amino-amides indicating an inherently higher potency of the cyclic piperidine series. Amide-linked local anesthetics did not impair the amplitude of the single-channel current but prolonged the time of the channel to be in the closed state derived as time constants "re from closed-time histograms. With etidocaine and lidocaine ~c was 133 and 7.2 ms, and proved to be independent of concentration. With the most potent bupivacaine time constants of wash in and wash out were 1.8 and 5.2 s for 600 nM bupivacaine. After lowering the extracellular pH from 7.4 to 6.6, externally applied bupivacaine showed a reduced potency, whereas at higher pH of 8.2 the block was slightly enhanced. Intracellular pH of 6.4, 7.2, 8.0 had almost no effect on internal bupivacaine block.It is concluded that local anesthetics block the flicker K + channel by impeding its gating but not its conductance. The slow blocker bupivacaine and the fast blocker lidocaine compete for the same receptor. Lipophilic interactions are of importance for blockade but besides a hydrophobic pathway, there exists also a hydrophilic pathway to the binding site which could only be reached from the cytoplasmic side of the membrane. Under physiological conditions, blockade of the flicker K § channel which is more sensitive to bupivacaine than the Na § channel might lead via

show abstract

Section: Introductionmentioning

confidence: 93%

Section: A New Mode Of Nerve Blockmentioning

confidence: 99%

Local anesthetics potently block a potential insensitive potassium channel in myelinated nerve.

Bräu

Nau

Hempelmann

et al. 1995

The Journal of General Physiology

View full text Add to dashboard Cite

show abstract

“…Transients do not occur during exposure to lidocaine (Raymond & Gissen, 1987), which, like halothane, preferentially inhibits Na+ currents, and also inhibits gq in frog node (Arhem & Frankenhaeuser, 1974).…”

Section: General Anaesthetics and Axon Excitability Threshold Transiementioning

confidence: 99%

Effects of halothane and enflurane on firing threshold of frog myelinated axons.

Butterworth

Raymond

Roscoe

1989

The Journal of Physiology

View full text Add to dashboard Cite

SUMMARY1. Firing thresholds and conduction latencies of single myelinated axons in frog sciatic nerves were monitored during impulse activity in vitro. Resting threshold and the activity dependence of threshold were studied as a function of the concentration of two inhalational anaesthetic agents, halothane and enflurane.2. At concentrations comparable to those obtained during general anaesthesia both agents produced biphasic effects on the resting threshold. A step increase in the partial pressure of anaesthetic was followed first by a transient lowering of threshold, then by a slow rise to a steady-state level above the original baseline.Step decreases in anaesthetic were followed by transient rises before threshold dropped. Transients lasted 20-30 min. During these threshold transients, the average latency of impulse conduction changed monotonically. The prolongation of latency following an increase in anaesthetic was progressive, reaching steady state concurrently with threshold (20 min to > 1 h).3. The anaesthetics reduced the long-lasting increased threshold ('depression') which normally follows repetitive impulse activity in axon membrane.4. These actions of halothane at concentrations of 0-25-2-7 % (014-P154 mM) and enflurane at concentrations of 0-62-3-08 % (0-35-1-73 mM) on resting threshold and on the activity-dependent increase in threshold increased monotonically with anaesthetic concentration.5. The effects on excitability at steady state are consistent with block of voltagedependent Na+ and K+ channels by these inhalational agents. Reduced depression may occur because the anaesthetics reduce the net ion transfer per impulse, slowing the substrate-driven Na+-K+-ATPase and thereby reducing electrogenic hyperpolarization.6. The finding that general anaesthetics inhibit depression at clinically relevant concentrations supports the possibility that general anaesthesia is produced by inhibition of processes that modulate excitability of nerve membrane. We suggestThe authors' names are in alphabetical order.

show abstract

“…7 Cooling-induced alterations in the vascular distribution of local anesthetic might delay or prevent the arrival of the anesthetic at the site of action, 8 affecting the uptake of local anesthetic from the nerve membrane.…”

Section: Discussionmentioning

confidence: 99%

The Role of Temperature in the Action of Mepivacaine

Dabarakis

Tsirlis

Parisis

et al. 2006

Anesthesia Progress

View full text Add to dashboard Cite

The role of temperature in the action of local anesthetics was studied in 20 healthy young volunteers with plain 3% mepivacaine injected periapically twice in their maxillary first premolar, the first time with the solution at a temperature of 20ЊC and the second time at 4ЊC. The pulpal response was measured with a pulp tester every minute. The onset of pulp anesthesia was found to be of no statistical difference between 20ЊC and 4ЊC. On the other hand, mepivacaine at a temperature of 4ЊC was found to have a statistically significant longer duration of action. Our conclusion is that the drop in temperature of mepivacaine from 20ЊC to 4ЊC provides a longer duration of pulpal anesthesia.Key Words: Temperature; Mepivacaine; Local anesthesia; Mechanism of action, onset, duration. It is well known since ancient times that the placement of something cold (eg, ice) produces anesthesia at the specific site of its placement.1 Moreover, the effect of lidocaine in blocking nerve impulses both in vitro and in vivo is potentiated by cooling.2-4 The nerve-blocking effect of lidocaine is also reported as being potentiated by increasing the temperature above 37ЊC.2 In other studies, the potency of various tertiary amine local anesthetics in impairing the excitability of frog skeletal muscle was markedly enhanced by an increase in temperature from 20ЊC to 30ЊC, and enhancement of the local anesthetic effects was also produced by a decrease in temperature to 5ЊC.5 Temperature may thus be an interesting physical variable in the study of nerve-blocking mechanisms. Given the absence in the dental literature of studies about the implications of temperature in the action of local anesthetics, the purpose of this preliminary study is to investigate the effects on the onset and the duration of pulpal anesthesia caused by lowering the temperature of the injected plain 3% mepivacaine from 20ЊC to 4ЊC. METHODSTwenty healthy young volunteers (12 women and 8 men, age 21-23 years) who were students in the Dental School of Aristotle University of Thessaloniki were included in this study. Before agreeing to participate in the study, each subject signed a relevant consent that included a brief description of the purpose and the therapeutic procedures involved. All the experimental procedures were conducted in accordance with the protocols outlined by Aristotle University of Thessaloniki regarding the recommended standard practices for Biological Investigations.For each subject, 0.25 mL of 3% plain mepivacaine (Mepivastesin, 3M ESPE AG, ESPE Platz, D-82229 Seefeld, Germany) was slowly injected periapically with local infiltration in the maxillary first premolar (having no previous restorative treatment) in 2 appointments scheduled 1 week apart with the same tooth and by the same protocol. All injections were made with standard disposable 1-mL insulin syringes and 30-gauge needles. The quantity of 0.25 mL of mepivacaine was chosen after preliminary experiments as an appropriate dose because we did not want the total duration of the experiment to ...

show abstract

Mechanisms of Differential Nerve Block

Cited by 38 publications

References 151 publications

Local anesthetics potently block a potential insensitive potassium channel in myelinated nerve.

Local anesthetics potently block a potential insensitive potassium channel in myelinated nerve.

Effects of halothane and enflurane on firing threshold of frog myelinated axons.

The Role of Temperature in the Action of Mepivacaine

Contact Info

Product

Resources

About