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Beneficial effects of Gelsemium-based treatment against paclitaxel-induced painful symptoms

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Abstract

Chemotherapeutic drugs induce various side effects including painful peripheral neuropathy that represents a major concern. The widely used anticancer drug paclitaxel causes neurological side effects such as burning pain, allodynia, and hyperalgesia. Neuroprotective substances that may effectively counteract paclitaxel-induced neuropathic symptoms are needed. Here, we investigated the potential of Gelsemium sempervirens (GS) to counteract paclitaxel-evoked painful neuropathy in rats. Using the von Frey hair and acetone behavioral tests, we investigated the potential of GS centesimal (C) dilutions 3, 5, and 9C to prevent or to correct paclitaxel-induced cold allodynia and mechanical allodynia/hyperalgesia involved in neuropathic pain. We found that a prophylactic or corrective treatment with GS dilutions prevented or suppressed PAC-evoked cold allodynia and mechanical allodynia/hyperalgesia, by reversing to normal, decreased cold thermal and mechanical pain thresholds of PAC-treated rats. In particular, preventive or corrective treatments with GS dilution 3C counteracted PAC-evoked allodynic and hyperalgesic responses. Also, GS dilution 5C (in a lesser extent than 3C) significantly reduced PAC-induced mechanical allodynia/hyperalgesia while GS dilution 9C was ineffective. PAC-evoked neuropathic symptoms were efficiently reduced after 1 week treatment with GS dilutions 3 or 5C and the beneficial action increased after 2 weeks. GS dilutions, particularly 3C, also counteracted or prevented PAC-induced sciatic nerve axon alterations and decreased the density of intraepidermal nerve fibers. Altogether, these results obtained in the rat preclinical model suggest that GS dilution-based treatment may constitute an interesting option to explore for the long-term management of pain without undesirable effects.

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Abbreviations

C:

Centesimal

GS:

Gelsemium sempervirens

PAC:

Paclitaxel

SC:

Spinal cord

W:

Water

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Acknowledgements

This work was supported by grants from the University of Strasbourg and INSERM.

Funding

The study was granted by the University of Strasbourg and INSERM.

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Authors and Affiliations

  1. 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 Médecine, 11 rue Humann, 67000, Strasbourg, France

    Ludivine Vitet, Christine Patte-Mensah, Ayikoé-Guy Mensah-Nyagan & Laurence Meyer

  2. Laboratoires BOIRON, Sainte-Foy-lès-Lyon, France

    Naoual Boujedaini

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  1. Ludivine Vitet
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  2. Christine Patte-Mensah
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  3. Naoual Boujedaini
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  4. Ayikoé-Guy Mensah-Nyagan
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  5. Laurence Meyer
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Correspondence to Ayikoé-Guy Mensah-Nyagan or Laurence Meyer.

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Conflict of interest

BOIRON financially supported the project, provided the treatments, but did not take legal responsibility for the study, which was sponsored by the University of Strasbourg and INSERM. NB from BOIRON contributed to the study design but did not participate in the realization of the study or in data analysis and interpretation.

Ethical approval

Animal care and manipulations were performed according to The European Community Council Directives (2010/63/UE) and under the supervision of authorized investigators. All experiments performed minimized the number of animals used and their suffering in accordance with the Alsace Department of Veterinary Public Health Guide for the Care and Use of Laboratory Animals. A national project authorization was delivered by the French Ministry of Higher Education and Research and by CREMEAS a local ethical committee (Project authorization number 9373). The experiments also followed the International Association for the Study of Pain ethical guidelines.

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Ayikoé-Guy Mensah-Nyagan and Laurence Meyer have co-seniority

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Vitet, L., Patte-Mensah, C., Boujedaini, N. et al. Beneficial effects of Gelsemium-based treatment against paclitaxel-induced painful symptoms. Neurol Sci 39, 2183–2196 (2018). https://doi.org/10.1007/s10072-018-3575-z

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