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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| Format: | Article |
| Language: | English |
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Elsevier
2021-08-01
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| Series: | Neurobiology of Pain |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452073X21000180 |
| _version_ | 1818403873774108672 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T08:31:11Z |
| format | Article |
| id | doaj.art-29e345b034294985b0e4b26dc6a669bd |
| institution | Directory Open Access Journal |
| issn | 2452-073X |
| language | English |
| last_indexed | 2024-12-14T08:31:11Z |
| publishDate | 2021-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Pain |
| spelling | doaj.art-29e345b034294985b0e4b26dc6a669bd2022-12-21T23:09:31ZengElsevierNeurobiology of Pain2452-073X2021-08-0110100077An adolescent rat model of vincristine-induced peripheral neuropathyAi-Ling Li0Jonathon D. Crystal1Yvonne Y. Lai2Tammy J. Sajdyk3Jamie L. Renbarger4Andrea G. Hohmann5Psychological and Brain Sciences, Indiana University, Bloomington, IN, USAPsychological and Brain Sciences, Indiana University, Bloomington, IN, USA; Program in Neuroscience, Indiana University, Bloomington, IN, USAPsychological and Brain Sciences, Indiana University, Bloomington, IN, USADepartment of Pediatrics, School of Medicine, Indiana University, Indianapolis, IN, USADepartment of Pediatrics, School of Medicine, Indiana University, Indianapolis, IN, USAPsychological and Brain Sciences, Indiana University, Bloomington, IN, USA; Gill Center for Biomolecular Science, Indiana University, Bloomington, IN, USA; Program in Neuroscience, Indiana University, Bloomington, IN, USA; Corresponding author at: Department of Psychological and Brain Sciences, Indiana University, 1101 E 10th Street, Bloomington, IN 47405-7007, USA.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.http://www.sciencedirect.com/science/article/pii/S2452073X21000180Chemotherapy-induced peripheral neuropathyAdolescenceExerciseObesityNeuropathic pain |
| spellingShingle | 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 Neurobiology of Pain Chemotherapy-induced peripheral neuropathy Adolescence Exercise Obesity Neuropathic pain |
| title | 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_short | An adolescent rat model of vincristine-induced peripheral neuropathy |
| title_sort | adolescent rat model of vincristine induced peripheral neuropathy |
| topic | Chemotherapy-induced peripheral neuropathy Adolescence Exercise Obesity Neuropathic pain |
| url | http://www.sciencedirect.com/science/article/pii/S2452073X21000180 |
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