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Body temperature homeostasis is accurately regulated by complex feedback-driven neuronal mechanisms, which involve a multitude of thermoregulatory pathways. Thus, core temperature is constantly maintained within a narrow range. As one of the most effective regulatory systems skin temperature is dependent on skin blood flow. Skin blood flow in turn is highly dependent on sympathetic activity. Regional anaesthesia leads to blockade not only of somatosensory and motor nerve fibres but also of sympathetic fibres. As a consequence, vasoconstrictor tonic activity is abrogated and a vasodilation leads to an increase in skin blood flow and temperature. The aim of this review was to summarize the general physiology of thermoregulation and skin temperature as well as the alterations during regional anaesthesia. The main focus was the usefulness of measuring skin temperature as an indicator of regional anaesthesia success. According to the available literature, assessment of skin temperature can indeed serve to predict success of regional anaesthesia. Hence, it is important to realize that relevant and reliable temperature increase is only seen in the most distal body parts, ie fingers and toes. More proximally, temperature changes are frequently small and inconsistent, which means that assessment of block levels is not possible by temperature measurement. Furthermore, relevant skin temperature increases will only be observed in patients, which are initially vasoconstricted. In conclusion, measurement of skin temperature represents a reliable and feasible diagnostic tool to assess and predict the success or failure of regional anaesthesia procedures, especially in patients in which sensory testing is impossible. [ABSTRACT FROM AUTHOR]

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Background and Purpose: The non-selective sodium channel inhibitor mexiletine has been found to be effective in several animal models of chronic pain and has become popular in the clinical setting as an orally available alternative to lidocaine. It remains unclear why patients with monogenic pain disorders secondary to gain-of-function SCN9a mutations benefit from a low systemic concentration of mexiletine, which does not usually induce adverse neurological side effects. The aim of this study was, therefore, to investigate the biophysical effects of mexiletine on the L858F primary erythromelalgia NaV 1.7 mutation in vitro.Experimental Approach: Human wild-type and L858F-mutated NaV 1.7 channels were expressed in HEK293A cells. Whole-cell currents were recorded by voltage-clamp techniques to characterize the effect of mexiletine on channel gating properties.Key Results: While the concentration-dependent tonic block of peak currents by mexiletine was similar in wild-type and L858F channels, phasic block was more pronounced in cells transfected with the L858F mutation. Moreover, mexiletine substantially shifted the pathologically-hyperpolarized voltage-dependence of steady-state activation in L858F-mutated channels towards wild-type values and the voltage-dependence of steady-state fast inactivation was shifted to more hyperpolarized potentials, leading to an overall reduction in window currents.Conclusion and Implications: Mexiletine has a normalizing effect on the pathological gating properties of the L858F gain-of-function mutation in NaV 1.7, which, in part, might explain the beneficial effects of systemic treatment with mexiletine in patients with gain-of-function sodium channel disorders. [ABSTRACT FROM AUTHOR]

Background and Purpose The non-selective sodium channel inhibitor mexiletine has been found to be effective in several animal models of chronic pain and has become popular in the clinical setting as an orally available alternative to lidocaine. It remains unclear why patients with monogenic pain disorders secondary to gain-of-function SCN9a mutations benefit from a low systemic concentration of mexiletine, which does not usually induce adverse neurological side effects. The aim of this study was, therefore, to investigate the biophysical effects of mexiletine on the L858 F primary erythromelalgia NaV1.7 mutation in vitro. Experimental Approach Human wild-type and L858 F-mutated NaV1.7 channels were expressed in HEK293A cells. Whole-cell currents were recorded by voltage-clamp techniques to characterize the effect of mexiletine on channel gating properties. Key Results While the concentration-dependent tonic block of peak currents by mexiletine was similar in wild-type and L858 F channels, phasic block was more pronounced in cells transfected with the L858 F mutation. Moreover, mexiletine substantially shifted the pathologically-hyperpolarized voltage-dependence of steady-state activation in L858 F-mutated channels towards wild-type values and the voltage-dependence of steady-state fast inactivation was shifted to more hyperpolarized potentials, leading to an overall reduction in window currents. Conclusion and Implications Mexiletine has a normalizing effect on the pathological gating properties of the L858 F gain-of-function mutation in NaV1.7, which, in part, might explain the beneficial effects of systemic treatment with mexiletine in patients with gain-of-function sodium channel disorders. [ABSTRACT FROM AUTHOR]