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      Electroporation technique for joint pain – Pilot feasibility study on TMD patients

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          Abstract

          Objective(s)

          It is well appreciated that traditional analgesic delivery routes used to treat pain associated with temporomandibular disorder (TMD) often have harmful unintended side effects as a consequence of systemic distribution. Further, localized delivery of analgesic medication via intra‐articular injections involves a different set of issues limiting their clinical viability. As an option, transdermal analgesic delivery provides for prolonged pain relief and flexibility in dose administration, while limiting systemic exposure and minimizing adverse events. Incorporation of a novel electroporation technique may further increase transdermal drug penetration into synovial tissue/fluid and enhance pain reduction. The present feasibility study compares the effectiveness of an electroporation‐enhanced transdermal application of diclofenac sodium to a conventional intra‐articular injection of triamcinolone acetonide suspension (corticosteroids) to treat patients with TMD associated pain.

          Methods

          Pre‐ and post‐treatment maximal incisal mouth opening (MIO), pain visual analog scale (VAS) and surface electromyography (EMG) of 22 patients treated with electroporation‐enhanced diclofenac and 37 patients treated with corticosteroids injections were collected and analyzed.

          Results

          In general, patients treated with electroporation exhibited better results in terms of pain improvement (corrected p‐value = .01) compared to the standard treatment, but both methods were similarly effective for improvement of MIO (corrected p‐value = .71) and improvement of all EMG indices (corrected p‐values ≥ .05).

          Conclusion

          The enhancing effect of electroporation in transdermal delivery of diclofenac sodium was demonstrated by decreased pain, increase MIO and EMG improvement to normal values. Its analgesic and inflammatory results are comparable with standard treatment offered by corticosteroids.

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          Most cited references27

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          Electroporation-based technologies for medicine: principles, applications, and challenges.

          When high-amplitude, short-duration pulsed electric fields are applied to cells and tissues, the permeability of the cell membranes and tissue is increased. This increase in permeability is currently explained by the temporary appearance of aqueous pores within the cell membrane, a phenomenon termed electroporation. During the past four decades, advances in fundamental and experimental electroporation research have allowed for the translation of electroporation-based technologies to the clinic. In this review, we describe the theory and current applications of electroporation in medicine and then discuss current challenges in electroporation research and barriers to a more extensive spread of these clinical applications.
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            Temporomandibular disorders and oral health-related quality of life. A systematic review.

            Oral health-related quality of life (OHRQoL) is considered an important aspect of different oral conditions. It has also gained increased attention in temporomandibular disorders (TMDs) in recent years. The purpose of this study was to systematically review the literature on OHRQoL and TMDs. A systematic search of the dental literature was performed using the Medline and Cochrane Library databases, supplemented by a hand search. Various combinations of search terms related to OHRQoL and TMDs were used. Among numerous titles found in Medline, abstracts and eventually full papers of potential interest were reviewed. Twelve papers fulfilled the inclusion criteria and were included in the review. Most studies used the Oral Health Impact Profile, an instrument with good psychometric properties, for evaluation. All articles described a substantial impact on OHRQoL in TMD patients. Only a small proportion of all patients, a few percent, reported no impact at all. The difference between men and women was small and not significant. The impact appeared to be more pronounced in patients with more signs and symptoms. The perceived impact of pain on OHRQoL seems to be substantial. Two studies found that the impact increased with age among TMD patients. The reviewed studies convincingly demonstrated that OHRQoL was negatively affected among TMD patients.
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              Skin electroporation for transdermal and topical delivery.

              Electroporation is the transitory structural perturbation of lipid bilayer membranes due to the application of high voltage pulses. Its application to the skin has been shown to increase transdermal drug delivery by several orders of magnitude. Moreover, electroporation, used alone or in combination with other enhancement methods, expands the range of drugs (small to macromolecules, lipophilic or hydrophilic, charged or neutral molecules) which can be delivered transdermally. Molecular transport through transiently permeabilized skin by electroporation results mainly from enhanced diffusion and electrophoresis. The efficacy of transport depends on the electrical parameters and the physicochemical properties of drugs. The in vivo application of high voltage pulses is well tolerated but muscle contractions are usually induced. The electrode and patch design is an important issue to reduce the discomfort of the electrical treatment in humans.
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                Author and article information

                Contributors
                gmtartaglia@gmail.com
                Journal
                Clin Exp Dent Res
                Clin Exp Dent Res
                10.1002/(ISSN)2057-4347
                CRE2
                Clinical and Experimental Dental Research
                John Wiley and Sons Inc. (Hoboken )
                2057-4347
                14 October 2020
                December 2020
                : 6
                : 6 ( doiID: 10.1002/cre2.v6.6 )
                : 642-649
                Affiliations
                [ 1 ] Department of Medicine, Surgery and Dentistry, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico University of Milan Milano Italy
                [ 2 ] SST Dental Clinic Segrate Italy
                [ 3 ] San Francisco Veterans Affairs Health Care System, Department of Oral & Maxillofacial Surgery University of California, San Francisco San Francisco California USA
                Author notes
                [*] [* ] Correspondence

                Gianluca Martino Tartaglia, Department of Medicine, Surgery and Dentistry, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, University of Milan, Milano, Italy.

                SST Dental Clinic, Segrate, Italy.

                Email: gmtartaglia@ 123456gmail.com

                Author information
                https://orcid.org/0000-0001-7062-5143
                Article
                CRE2327
                10.1002/cre2.327
                7745067
                33280278
                74350fa0-cffb-4d4e-9542-b70e64a34e58
                © 2020 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 March 2020
                : 12 August 2020
                : 24 August 2020
                Page count
                Figures: 2, Tables: 2, Pages: 8, Words: 5781
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                December 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.5 mode:remove_FC converted:17.12.2020

                anti‐inflammatory,electroporation,temporomandibular joint,transdermal drug delivery

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