An adolescent rat model of vincristine-induced peripheral neuropathy

Childhood acute lymphoblastic leukemia (ALL) is a significant clinical problem that can be effectively treated with vincristine, a vinca alkaloid-based chemotherapeutic agent. However, nearly all children receiving vincristine treatment develop vincristine-induced peripheral neuropathy (VIPN). The i...

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Autores principales:	Ai-Ling Li, Jonathon D. Crystal, Yvonne Y. Lai, Tammy J. Sajdyk, Jamie L. Renbarger, Andrea G. Hohmann
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Chemotherapy-induced peripheral neuropathy Adolescence Exercise Obesity Neuropathic pain Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/29e345b034294985b0e4b26dc6a669bd
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spelling	oai:doaj.org-article:29e345b034294985b0e4b26dc6a669bd2021-11-18T04:50:53ZAn adolescent rat model of vincristine-induced peripheral neuropathy2452-073X10.1016/j.ynpai.2021.100077https://doaj.org/article/29e345b034294985b0e4b26dc6a669bd2021-08-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2452073X21000180https://doaj.org/toc/2452-073XChildhood acute lymphoblastic leukemia (ALL) is a significant clinical problem that can be effectively treated with vincristine, a vinca alkaloid-based chemotherapeutic agent. However, nearly all children receiving vincristine treatment develop vincristine-induced peripheral neuropathy (VIPN). The impact of adolescent vincristine treatment across the lifespan remains poorly understood. We, consequently, developed an adolescent rodent model of VIPN which can be utilized to study possible long term consequences of vincristine treatment in the developing rat. We also evaluated the therapeutic efficacy of voluntary exercise and potential impact of obesity as a genetic risk factor in this model on the development and maintenance of VIPN. Out of all the dosing regimens we evaluated, the most potent VIPN was produced by fifteen consecutive daily intraperitoneal (i.p.) vincristine injections at 100 µg/kg/day, throughout the critical period of adolescence from postnatal day 35 to 49. With this treatment, vincristine-treated animals developed hypersensitivity to mechanical and cold stimulation of the plantar hind paw surface, which outlasted the period of vincristine treatment and resolved within two weeks following the cessation of vincristine injection. By contrast, impairment in grip strength gain was delayed by vincristine treatment, emerging shortly following the termination of vincristine dosing, and persisted into early adulthood without diminishing. Interestingly, voluntary wheel running exercise prevented the development of vincristine-induced hypersensitivities to mechanical and cold stimulation. However, Zucker fa/fa obese animals did not exhibit higher risk of developing VIPN compared to lean rats. Our studies identify sensory and motor impairments produced by vincristine in adolescent animals and support the therapeutic efficacy of voluntary exercise for suppressing VIPN in developing rats.Ai-Ling LiJonathon D. CrystalYvonne Y. LaiTammy J. SajdykJamie L. RenbargerAndrea G. HohmannElsevierarticleChemotherapy-induced peripheral neuropathyAdolescenceExerciseObesityNeuropathic painNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENNeurobiology of Pain, Vol 10, Iss , Pp 100077- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Chemotherapy-induced peripheral neuropathy Adolescence Exercise Obesity Neuropathic pain Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Chemotherapy-induced peripheral neuropathy Adolescence Exercise Obesity Neuropathic pain Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Ai-Ling Li Jonathon D. Crystal Yvonne Y. Lai Tammy J. Sajdyk Jamie L. Renbarger Andrea G. Hohmann An adolescent rat model of vincristine-induced peripheral neuropathy
description	Childhood acute lymphoblastic leukemia (ALL) is a significant clinical problem that can be effectively treated with vincristine, a vinca alkaloid-based chemotherapeutic agent. However, nearly all children receiving vincristine treatment develop vincristine-induced peripheral neuropathy (VIPN). The impact of adolescent vincristine treatment across the lifespan remains poorly understood. We, consequently, developed an adolescent rodent model of VIPN which can be utilized to study possible long term consequences of vincristine treatment in the developing rat. We also evaluated the therapeutic efficacy of voluntary exercise and potential impact of obesity as a genetic risk factor in this model on the development and maintenance of VIPN. Out of all the dosing regimens we evaluated, the most potent VIPN was produced by fifteen consecutive daily intraperitoneal (i.p.) vincristine injections at 100 µg/kg/day, throughout the critical period of adolescence from postnatal day 35 to 49. With this treatment, vincristine-treated animals developed hypersensitivity to mechanical and cold stimulation of the plantar hind paw surface, which outlasted the period of vincristine treatment and resolved within two weeks following the cessation of vincristine injection. By contrast, impairment in grip strength gain was delayed by vincristine treatment, emerging shortly following the termination of vincristine dosing, and persisted into early adulthood without diminishing. Interestingly, voluntary wheel running exercise prevented the development of vincristine-induced hypersensitivities to mechanical and cold stimulation. However, Zucker fa/fa obese animals did not exhibit higher risk of developing VIPN compared to lean rats. Our studies identify sensory and motor impairments produced by vincristine in adolescent animals and support the therapeutic efficacy of voluntary exercise for suppressing VIPN in developing rats.
format	article
author	Ai-Ling Li Jonathon D. Crystal Yvonne Y. Lai Tammy J. Sajdyk Jamie L. Renbarger Andrea G. Hohmann
author_facet	Ai-Ling Li Jonathon D. Crystal Yvonne Y. Lai Tammy J. Sajdyk Jamie L. Renbarger Andrea G. Hohmann
author_sort	Ai-Ling Li
title	An adolescent rat model of vincristine-induced peripheral neuropathy
title_short	An adolescent rat model of vincristine-induced peripheral neuropathy
title_full	An adolescent rat model of vincristine-induced peripheral neuropathy
title_fullStr	An adolescent rat model of vincristine-induced peripheral neuropathy
title_full_unstemmed	An adolescent rat model of vincristine-induced peripheral neuropathy
title_sort	adolescent rat model of vincristine-induced peripheral neuropathy
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/29e345b034294985b0e4b26dc6a669bd
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An adolescent rat model of vincristine-induced peripheral neuropathy

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