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      • Record: found
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      Topical Treatments for Localized Neuropathic Pain

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          Abstract

          Purpose of Review

          Topical therapeutic approaches in localized neuropathic pain (LNP) syndromes are increasingly used by both specialists and general practitioners, with a potentially promising effect on pain reduction. In this narrative review, we describe the available compounds for topical use in LNP syndromes and address their potential efficacy according to the literature.

          Recent Findings

          Local anaesthetics (e.g., lidocaine, bupivacaine and mepivacaine), as well as general anaesthetic agents (e.g., ketamine), muscle relaxants (e.g., baclofen), capsaicin, anti-inflammatory drugs (e.g., diclofenac), salicylates, antidepressants (e.g., amitriptyline and doxepin), α2 adrenergic agents (e.g., clonidine), or even a combination of them have been tested in various applications for the treatment of LNP. Few of them have reached a sufficient level of evidence to support systematic use as treatment options.

          Summary

          Relatively few systemic side effects or drug–drug interactions and satisfactory efficacy seem to be the benefits of topical treatments. More well-organized and tailored studies are necessary for the further conceptualization of topical treatments for LNP.

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          Most cited references83

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          A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons.

          A Akopian, L Sivilotti, J Wood (1996)
          Dorsal root ganglion sensory neurons associated with C-fibres, many of which are activated by tissue-damage, express an unusual voltage-gated sodium channel that is resistant to tetrodotoxin. We report here that we have identified a 1,957 amino-acid sodium channel in these cells that shows 65% identity with the rat cardiac tetrodotoxin-insensitive sodium channel, and is not expressed in other peripheral and central neurons, glia or non-neuronal tissues. In situ hybridization shows that the channel is expressed only by small-diameter sensory neurons in neonatal and adult dorsal root and trigeminal ganglia. The channel is resistant to tetrodotoxin when expressed in Xenopus oocytes. The electrophysiological and pharmacological properties of the expressed channel are similar to those described for the small-diameter sensory neuron tetrodotoxin-resistant sodium channels. As some noxious input into the spinal cord is resistant to tetrodotoxin, block of expression or function of such a C-fibre-restricted sodium channel may have a selective analgesic effect.
          Article 0 comments Cited 175 times – based on 0 reviews     Review now
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            alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role.

            Sohrab Z. Khan, Jonathan Jones, Mhairi C. Ferguson (1999)
            Clonidine has proved to be a clinically useful adjunct in clinical anaesthetic practice as well as in chronic pain therapy because it has both anaesthetic and analgesic-sparing activity. The more selective alpha-2 adrenoceptor agonists, dexmedetomidine and mivazerol, may also have a role in providing haemodynamic stability in patients who are at risk of peri-operative ischaemia. The side-effects of hypotension and bradycardia have limited the routine use of alpha-2 adrenoceptor agonists. Investigations into the molecular pharmacology of alpha-2 adrenoceptors have elucidated their role in the control of wakefulness, blood pressure and antinociception. We discuss the pharmacology of alpha-2 adrenoceptors and their therapeutic role in this review. The alpha-2 adrenoceptor agonists are agonists at imidazoline receptors which are involved in central blood pressure control. Selective imidazoline agonists are now available for clinical use as antihypertensive agents and their pharmacology is discussed.
            Article 0 comments Cited 133 times – based on 0 reviews     Review now
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              Contribution of Na(v)1.8 sodium channels to action potential electrogenesis in DRG neurons.

              Muthukrishnan Renganathan, Theodore R. Cummins, Stephen G. Waxman (2001)
              C-type dorsal root ganglion (DRG) neurons can generate tetrodotoxin-resistant (TTX-R) sodium-dependent action potentials. However, multiple sodium channels are expressed in these neurons, and the molecular identity of the TTX-R sodium channels that contribute to action potential production in these neurons has not been established. In this study, we used current-clamp recordings to compare action potential electrogenesis in Na(v)1.8 (+/+) and (-/-) small DRG neurons maintained for 2-8 h in vitro to examine the role of sodium channel Na(v)1.8 (alpha-SNS) in action potential electrogenesis. Although there was no significant difference in resting membrane potential, input resistance, current threshold, or voltage threshold in Na(v)1.8 (+/+) and (-/-) DRG neurons, there were significant differences in action potential electrogenesis. Most Na(v)1.8 (+/+) neurons generate all-or-none action potentials, whereas most of Na(v)1.8 (-/-) neurons produce smaller graded responses. The peak of the response was significantly reduced in Na(v)1.8 (-/-) neurons [31.5 +/- 2.2 (SE) mV] compared with Na(v)1.8 (+/+) neurons (55.0 +/- 4.3 mV). The maximum rise slope was 84.7 +/- 11.2 mV/ms in Na(v)1.8 (+/+) neurons, significantly faster than in Na(v)1.8 (-/-) neurons where it was 47.2 +/- 1.3 mV/ms. Calculations based on the action potential overshoot in Na(v)1.8 (+/+) and (-/-) neurons, following blockade of Ca(2+) currents, indicate that Na(v)1.8 contributes a substantial fraction (80-90%) of the inward membrane current that flows during the rising phase of the action potential. We found that fast TTX-sensitive Na(+) channels can produce all-or-none action potentials in some Na(v)1.8 (-/-) neurons but, presumably as a result of steady-state inactivation of these channels, electrogenesis in Na(v)1.8 (-/-) neurons is more sensitive to membrane depolarization than in Na(v)1.8 (+/+) neurons, and, in the absence of Na(v)1.8, is attenuated with even modest depolarization. These observations indicate that Na(v)1.8 contributes substantially to action potential electrogenesis in C-type DRG neurons.
              Article 0 comments Cited 105 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Roberto Casale: robertocasale@habilita.it
                Journal
                Journal ID (nlm-ta): Curr Pain Headache Rep
                Journal ID (iso-abbrev): Curr Pain Headache Rep
                Title: Current Pain and Headache Reports
                Publisher: Springer US (New York )
                ISSN (Print): 1531-3433
                ISSN (Electronic): 1534-3081
                Publication date (Electronic): 7 March 2017
                Publication date PMC-release: 7 March 2017
                Publication date (Print): 2017
                Volume: 21
                Issue: 3
                Electronic Location Identifier: 15
                Affiliations
                [1 ]Department of High Technology Rehabilitation & Pain Rehabilitation Unit, Habilita Care and Research Hospitals, Via Bologna 1-24040, Zingonia di Ciserano (BG), Italy
                [2 ]ISNI 0000 0004 0622 8129, GRID grid.415070.7, Department of Physical and Rehabilitation Medicine, , General Hospital of Attica “KAT”, ; Athens, Greece
                [3 ]Department of Rehabilitation, Neurorehabilitation Unit, Habilita, Zingonia di Ciserano (BG), Italy
                Article
                Publisher ID: 615
                DOI: 10.1007/s11916-017-0615-y
                PMC ID: 5340828
                PubMed ID: 28271334
                SO-VID: 306bff40-d4bf-4b50-8dc0-4424e772ed8a
                Copyright © © The Author(s) 2017
                License:

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                Categories
                Subject: Neuropathic Pain (E Eisenberg, Section Editor)
                Custom metadata
                issue-copyright-statement © Springer Science+Business Media New York 2017

                ScienceOpen disciplines: Anesthesiology & Pain management
                Keywords: localized neuropathic pain,topical lidocaine,topical ketamine,topical baclofen,topical amitriptyline,topical clonidine
                Data availability:
                ScienceOpen disciplines: Anesthesiology & Pain management
                Keywords: localized neuropathic pain, topical lidocaine, topical ketamine, topical baclofen, topical amitriptyline, topical clonidine

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