Analgesic Effects of Topical Amitriptyline in Patients With Chemotherapy-Induced Peripheral Neuropathy: Mechanistic Insights From Studies in Mice
| العنوان: | Analgesic Effects of Topical Amitriptyline in Patients With Chemotherapy-Induced Peripheral Neuropathy: Mechanistic Insights From Studies in Mice |
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| المؤلفون: | Paola Principe, Virginie Penalba, Myriam Ducrocq, Séverine Hatton, Patrick Delmas, Jérôme Ruel, Camille Petitfils, Gilles Dietrich, Céline Greco, Anne-Laure Genevois |
| المساهمون: | Département de Pathologie [CHU Necker], Université Sorbonne Paris Cité (USPC)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPC), Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), AlgoTherapeutix, Modèles de Cellules Souches Malignes et Thérapeutiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Sante Active Edition, Ecole de l’Inserm Liliane-Bettencourt, Fondation Bettencourt-Schueller, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) |
| المصدر: | The Journal of Pain The Journal of Pain, 2021, 22 (4), pp.440-453. ⟨10.1016/j.jpain.2020.11.002⟩ |
| بيانات النشر: | HAL CCSD, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Administration, Topical, Pharmacology, Nociceptive Pain, Mice, 0302 clinical medicine, 030202 anesthesiology, voltage-gated sodium channels, Amitriptyline, Child, TRPA1 Cation Channel, Aged, 80 and over, Voltage-Gated Sodium Channel Blockers, Behavior, Animal, NAV1.7 Voltage-Gated Sodium Channel, Chronic pain, Peripheral Nervous System Diseases, Analgesics, Non-Narcotic, Middle Aged, 3. Good health, Neurology, Chemotherapy-induced peripheral neuropathy, Neuropathic pain, Nociceptor, analgesics, Female, medicine.drug, chemotherapy-induced peripheral neuropathy, Adult, Adolescent, Amitriptyline Hydrochloride, Analgesic, Antineoplastic Agents, NAV1.8 Voltage-Gated Sodium Channel, Young Adult, 03 medical and health sciences, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, medicine, Animals, Humans, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, NAV1.9 Voltage-Gated Sodium Channel, Aged, business.industry, nociceptive sensory neurons, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, Anesthesiology and Pain Medicine, Peripheral neuropathy, nociceptors, topical adminis-tration, Neurology (clinical), transient receptor potentialankyrin 1, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| الوصف: | International audience; Oral amitriptyline hydrochloride (amitriptyline) is ineffective against some forms of chronic pain and is often associated with dose-limiting adverse events. We evaluated the potential effectiveness of high-dose topical amitriptyline in a preliminary case series of chemotherapy-induced peripheral neuropathy patients and investigated whether local or systemic adverse events associated with the use of amitriptyline were present in these patients. We also investigated the mechanism of action of topically administered amitriptyline in mice. Our case series suggested that topical 10% amitriptyline treatment was associated with pain relief in chemotherapy-induced peripheral neuropathy patients, without the side effects associated with systemic absorption. Topical amitriptyline significantly increased mechanical withdrawal thresholds when applied to the hind paw of mice, and inhibited the firing responses of C-, Aβ- and Aδ-type peripheral nerve fibers in ex vivo skin-saphenous nerve preparations. Whole-cell patch-clamp recordings on cultured sensory neurons revealed that amitriptyline was a potent inhibitor of the main voltage-gated sodium channels (Nav1.7, Nav1.8, and Nav1.9) found in nociceptors. Calcium imaging showed that amitriptyline activated the transient receptor potential cation channel, TRPA1. Our case series indicated that high-dose 10% topical amitriptyline could alleviate neuropathic pain without adverse local or systemic effects. This analgesic action appeared to be mediated through local inhibition of voltage-gated sodium channels. Perspective: Our preliminary case series suggested that topical amitriptyline could provide effective pain relief for chemotherapy-induced peripheral neuropathy patients without any systemic or local adverse events. Investigation of the mechanism of this analgesic action in mice revealed that this activity was mediated through local inhibition of nociceptor Nav channels. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7a486a29f11f3dea5fd086fd5fd6a0e3Test https://hal.inrae.fr/hal-03084518/documentTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7a486a29f11f3dea5fd086fd5fd6a0e3 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |