Dissociation Constants of Local Anesthetics and Their Temperature Dependence

Kamaya, Hiroshi; Hayes, John J.; Ueda, I.

doi:10.1213/00000539-198311000-00012

Cited by 91 publications

(41 citation statements)

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“…10 It is possible that these effects of low temperature and local anesthetics on the kinetics of sodium channel inactivation are independent and merely additive as suggested by Harper et al 11 It is also known that cooling produces local anesthesia by itself. Moreover, Goto and Itano 12 and other researchers 13,14 have shown that the pK a of lidocaine increases as the temperature decreases. Thus, when lidocaine is injected at low temperature, a higher percentage of the local anesthetic will be present in the ionized form once the non-ionizing form of the anesthetic penetrates the neuron.…”

Section: Discussionmentioning

confidence: 88%

The Role of Temperature in the Action of Mepivacaine

Dabarakis

Tsirlis

Parisis

et al. 2006

Anesthesia Progress

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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 ...

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Section: Discussionmentioning

confidence: 88%

The Role of Temperature in the Action of Mepivacaine

Dabarakis

Tsirlis

Parisis

et al. 2006

Anesthesia Progress

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“…Based on our results, a greater pharmacological efficacy was found during the photoperiod, which was reflected by a shorter latency period and a longer duration of effect. These findings, albeit more easily explained in the context of the intrathecal block, may also be related to the influence of the increase in body temperature on the decline in the pKa of the local anaesthetic (Morf & Schibler, 2013), which therefore decreased the length of the latency period (Kamaya et al, 1983). The consequence of this decrease in the pKa is an increase in the non-ionised form of the local anaesthetic, which enhances its diffusion capacity and thus reduces the onset time of its effect, mainly at the end of the photoperiod.…”

Section: Discussionmentioning

confidence: 99%

The influence of women’s attachment style on the chronobiology of labour pain, analgesic consumption and pharmacological effect

Costa-Martins

Pereira

Martins

et al. 2014

Chronobiology International

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Circadian variation in biological rhythms has been identified as affecting both labour pain and the pharmacological properties of analgesics. In the context of pain, there is also a growing body of evidence suggesting the importance of adult attachment. The purpose of this study was to examine whether labour pain, analgesic consumption and pharmacological effect are significantly affected by the time of day, and to analyse whether this circadian variation is influenced by women's attachment style. This prospective observational study included a sample of 81 pregnant women receiving patientcontrolled epidural analgesia (PCEA). Attachment was assessed with the Adult Attachment ScaleRevised (AAS-R). The perceived intensity of labour pain in the early stage of labour (3 cm of cervical dilatation and before the administration of PCEA) was measured using a visual analogue scale (VAS).Pain was also indirectly assessed by measuring the consumption of anaesthetics. The latency period and the duration of effect were recorded for a chronopharmacology characterisation. Pain, as assessed with the VAS, was significantly higher in the night-time group than in the daytime group. An insecure attachment style was significantly associated with greater labour pain at 3 cm of cervical dilatation (p < 0.001) and before the beginning of analgesia (p < 0.001) as well as with higher analgesic consumption and lower pharmacological efficacy (p < 0.05). The time of day was significantly associated with the pharmacological effect: the latency period was longer at night, and the duration of the pharmacological effect was longer during the daytime. The interaction between time of day and attachment style was not significant for any of the study variables. Our results provide evidence of the importance of circadian variation in studying labour pain and the pharmacological effect of labour analgesia involving epidural blockage with a PCEA regimen. Moreover, although there was no evidence that attachment style influenced the circadian variation, these data emphasise that insecure attachment patterns are a risk factor for greater labour pain and analgesic consumption, which should be considered in pain management approaches.

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“…Previous studies have suggested that it may be due to an increased rate of passive diffusion across non-neural structures and/or a reduction in pKa, leading to an increase in the non-ionized fraction of local anesthetic that can cross the neural membranes [7][8][9]. Although we did not assess pKa in this study, it is possible that these values decreased with warming, thereby explaining -at least in part -the increased onset of sensory block noted in patients who received BT ropivacaine [12,[14][15][16].…”

Section: Discussionmentioning

confidence: 99%