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Allopregnanolone and Progesterone in Experimental Neuropathic Pain: Former and New Insights with a Translational Perspective

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Abstract

In the last decades, an active and stimulating area of research has been devoted to explore the role of neuroactive steroids in pain modulation. Despite challenges, these studies have clearly contributed to unravel the multiple and complex actions and potential mechanisms underlying steroid effects in several experimental conditions that mimic human chronic pain states. Based on the available data, this review focuses mainly on progesterone and its reduced derivative allopregnanolone (also called 3α,5α-tetrahydroprogesterone) which have been shown to prevent or even reverse the complex maladaptive changes and pain behaviors that arise in the nervous system after injury or disease. Because the characterization of new related molecules with improved specificity and enhanced pharmacological profiles may represent a crucial step to develop more efficient steroid-based therapies, we have also discussed the potential of novel synthetic analogs of allopregnanolone as valuable molecules for the treatment of neuropathic pain.

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Acknowledgements

This work was supported by Grants from Consejo Nacional de Investigaciones Científicas y Tecnológicas (PIP 112 20150100266), Fundación René Barón and Fundación Williams, Université de Strasbourg, Institut National de la Santé et de la Recherche Médicale, and Association Ti’toine de Normandie. These funding institutions/organizations had no role in the collection, analysis, and interpretation of data, in writing the report, and in the decision to submit the article for publication.

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Authors and Affiliations

  1. Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, C1121ABG, Buenos Aires, Argentina

    Susana Laura González

  2. Laboratorio de Nocicepción y Dolor Neuropático, Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490, C1428ADN, Buenos Aires, Argentina

    Susana Laura González, María Celeste Raggio & María Florencia Coronel

  3. Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques, INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Bâtiment 3 de la Faculté de Médicine, 11 rue Humann, 67 000, Strasbourg, France

    Laurence Meyer, Omar Taleb, Christine Patte-Mensah & Ayikoe Guy Mensah-Nyagan

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  1. Susana Laura González
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  2. Laurence Meyer
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  7. Ayikoe Guy Mensah-Nyagan
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Contributions

S.L.G and A.G.M-N conceived, designed, and wrote the manuscript. L.M., M.C.R., and C.P-M designed the figures. L.M., M.C.R., O.T., M.F.C., and C.P-M revised and critically contributed to the approved final version.

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Correspondence to Susana Laura González or Ayikoe Guy Mensah-Nyagan.

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González, S.L., Meyer, L., Raggio, M.C. et al. Allopregnanolone and Progesterone in Experimental Neuropathic Pain: Former and New Insights with a Translational Perspective. Cell Mol Neurobiol 39, 523–537 (2019). https://doi.org/10.1007/s10571-018-0618-1

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