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      Peripheral Nerve Conduction Block by High-Frequency Alternating Currents: A Systematic Review

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          Antiepileptic drugs for neuropathic pain and fibromyalgia - an overview of Cochrane reviews.

          Antiepileptic drugs have been used for treating different types of neuropathic pain, and sometimes fibromyalgia. Our understanding of quality standards in chronic pain trials has improved to include new sources of potential bias. Individual Cochrane reviews using these new standards have assessed individual antiepileptic drugs. An early review from this group, originally published in 1998, was titled 'Anticonvulsants for acute and chronic pain'. This overview now covers the neuropathic pain aspect of that original review, which was withdrawn in 2009. To provide an overview of the relative analgesic efficacy of antiepileptic drugs that have been compared with placebo in neuropathic pain and fibromyalgia, and to report on adverse events associated with their use. We included reviews published in theCochrane Database of Systematic Reviews up to August 2013 (Issue 7). We extracted information from each review on measures of efficacy and harm, and methodological details concerning the number of participants, the duration of studies, and the imputation methods used, in order to judge potential biases in available data.We analysed efficacy data for each painful condition in three tiers, according to outcome and freedom from known sources of bias. The first tier met current best standards - at least 50% pain intensity reduction over baseline (or its equivalent), without the use of last observation carried forward (LOCF) for dropouts, an intention-to-treat (ITT) analysis, in parallel group studies with at least 200 participants lasting eight weeks or more. The second tier used data from at least 200 participants where one or more of the above conditions were not met. The third tier of evidence related to data from fewer than 200 participants, or with several important methodological problems that limited interpretation. No studies reported top tier results.For gabapentin and pregabalin only we found reasonably good second tier evidence for efficacy in painful diabetic neuropathy and postherpetic neuralgia. In addition, for pregabalin, we found evidence of efficacy in central neuropathic pain and fibromyalgia. Point estimates of numbers needed to treat for an additional beneficial effect (NNTs) were in the range of 4 to 10 for the important outcome of pain intensity reduction over baseline of 50% or more.For other antiepileptic drugs there was no evidence (clonazepam, phenytoin), so little evidence that no sensible judgement could be made about efficacy (valproic acid), low quality evidence likely to be subject to a number of biases overestimating efficacy (carbamazepine), or reasonable quality evidence indicating little or no effect (lamotrigine, oxcarbazepine, topiramate). Lacosamide recorded such a trivial statistical superiority over placebo that it was unreliable to conclude that it had any efficacy where there was possible substantial bias.Any benefits of treatment came with a high risk of adverse events and withdrawal because of adverse events, but serious adverse events were not significantly raised, except with oxcarbazepine. Clinical trial evidence supported the use of only gabapentin and pregabalin in some neuropathic pain conditions (painful diabetic neuropathy, postherpetic neuralgia, and central neuropathic pain) and fibromyalgia. Only a minority of people achieved acceptably good pain relief with either drug, but it is known that quality of life and function improved markedly with the outcome of at least 50% pain intensity reduction. For other antiepileptic drugs there was no evidence, insufficient evidence, or evidence of a lack of effect; this included carbamazepine. Evidence from clinical practice and experience is that some patients can achieve good results with antiepileptics other than gabapentin or pregabalin.There is no firm evidence to answer the important pragmatic questions about which patients should have which drug, and in which order the drugs should be used. There is a clinical effectiveness research agenda to provide evidence about strategies rather than interventions, to produce the overall best results in a population, in the shortest time, and at the lowest cost to healthcare providers.
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            Reversible nerve conduction block using kilohertz frequency alternating current.

            The features and clinical applications of balanced-charge kilohertz frequency alternating currents (KHFAC) are reviewed. Preclinical studies of KHFAC block have demonstrated that it can produce an extremely rapid and reversible block of nerve conduction. Recent systematic analysis and experimentation utilizing KHFAC block have resulted in a significant increase in interest in KHFAC block, both scientifically and clinically.
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              Nerve conduction block utilising high-frequency alternating current.

              High-frequency alternating current (AC) waveforms have been shown to produce a quickly reversible nerve block in animal models, but the parameters and mechanism of this block are not well understood. A frog sciatic nerve/gastrocnemius muscle preparation was used to examine the parameters for nerve conduction block in vivo, and a computer simulation of the nerve membrane was used to identify the mechanism for block. The results indicated that a 100% block of motor activity can be accomplished with a variety of waveform parameters, including sinusoidal and rectangular waveforms at frequencies from 2 kHz to 20 kHz. A complete and reversible block was achieved in 34 out of 34 nerve preparations tested. The most efficient waveform for conduction block was a 3-5 kHz constant-current biphasic sinusoid, where block could be achieved with stimulus levels as low as 0.01 microCphase(-1). It was demonstrated that the block was not produced indirectly through fatigue. Computer simulation of high-frequency AC demonstrated a steady-state depolarisation of the nerve membrane, and it is hypothesised that the conduction block was due to this tonic depolarisation. The precise relationship between the steady-state depolarisation and the conduction block requires further analysis. The results of this study demonstrated that high-frequency AC can be used to produce a fast-acting, and quickly reversible nerve conduction block that may have multiple applications in the treatment of unwanted neural activity.
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                Author and article information

                Journal
                IEEE Transactions on Neural Systems and Rehabilitation Engineering
                IEEE Trans. Neural Syst. Rehabil. Eng.
                Institute of Electrical and Electronics Engineers (IEEE)
                1534-4320
                1558-0210
                June 2018
                June 2018
                : 26
                : 6
                : 1131-1140
                Article
                10.1109/TNSRE.2018.2833141
                29877837
                e8269e3c-6e0f-4346-b1c5-749801a69b5a
                © 2018
                History

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