Early life vincristine exposure evokes mechanical pain hypersensitivity in the developing rat
- PMID: 28722694
- PMCID: PMC5643007
- DOI: 10.1097/j.pain.0000000000000953
Early life vincristine exposure evokes mechanical pain hypersensitivity in the developing rat
Abstract
Vincristine (VNC) is commonly used to treat pediatric cancers, including the most prevalent childhood malignancy, acute lymphoblastic leukemia. Although clinical evidence suggests that VNC causes peripheral neuropathy in children, the degree to which pediatric chemotherapeutic regimens influence pain sensitivity throughout life remains unclear, in part because of the lack of an established animal model of chemotherapy-induced neuropathic pain during early life. Therefore, this study investigated the effects of VNC exposure between postnatal days (P) 11 and 21 on mechanical and thermal pain sensitivity in the developing rat. Low doses of VNC (15 or 30 μg/kg) failed to alter nociceptive withdrawal reflexes at any age examined compared with vehicle-injected littermate controls. Meanwhile, high dose VNC (60 μg/kg) evoked mechanical hypersensitivity in both sexes beginning at P26 that persisted until adulthood and included both static and dynamic mechanical allodynia. Hind paw withdrawal latencies to noxious heat and cold were unaffected by high doses of VNC, suggesting a selective effect of neonatal VNC on mechanical pain sensitivity. Gross and fine motor function appeared normal after VNC treatment, although a small decrease in weight gain was observed. The VNC regimen also produced a significant decrease in intraepidermal nerve fiber density in the hind paw skin by P33. Overall, the present results demonstrate that high-dose administration of VNC during the early postnatal period selectively evokes a mechanical hypersensitivity that is slow to emerge during adolescence, providing further evidence that aberrant sensory input during early life can have prolonged consequences for pain processing.
Conflict of interest statement
The authors declare that they have no conflicts of interest with any of the work presented in this manuscript.
Figures






Comment in
-
New model of vincristine-induced neuropathic pain in children: a first step towards prediction and prevention.Pain. 2017 Sep;158(9):1627-1628. doi: 10.1097/j.pain.0000000000000981. Pain. 2017. PMID: 28817415 Free PMC article. No abstract available.
Similar articles
-
Early life vincristine fails to prime developing pain pathways.Neurosci Lett. 2020 Feb 16;720:134764. doi: 10.1016/j.neulet.2020.134764. Epub 2020 Jan 17. Neurosci Lett. 2020. PMID: 31958538 Free PMC article.
-
Antiallodynic and anti-inflammatory effects of intrathecal R-PIA in a rat model of vincristine-induced peripheral neuropathy.Korean J Anesthesiol. 2020 Oct;73(5):434-444. doi: 10.4097/kja.19481. Epub 2020 Feb 12. Korean J Anesthesiol. 2020. PMID: 32046474 Free PMC article.
-
Neonatal vincristine administration modulates intrinsic neuronal excitability in the rat dorsal root ganglion and spinal dorsal horn during adolescence.Pain. 2019 Mar;160(3):645-657. doi: 10.1097/j.pain.0000000000001444. Pain. 2019. PMID: 30681983 Free PMC article.
-
Vincristine hyperalgesia in the rat: a model of painful vincristine neuropathy in humans.Neuroscience. 1996 Jul;73(1):259-65. doi: 10.1016/0306-4522(96)00020-6. Neuroscience. 1996. PMID: 8783247
-
Antinociceptive effect of Butea monosperma on vincristine-induced neuropathic pain model in rats.Toxicol Ind Health. 2013 Feb;29(1):3-13. doi: 10.1177/0748233711432573. Epub 2012 Jan 27. Toxicol Ind Health. 2013. PMID: 22287618
Cited by
-
New model of vincristine-induced neuropathic pain in children: a first step towards prediction and prevention.Pain. 2017 Sep;158(9):1627-1628. doi: 10.1097/j.pain.0000000000000981. Pain. 2017. PMID: 28817415 Free PMC article. No abstract available.
-
Critical Pronociceptive Role of Family 2 Voltage-Gated Calcium Channels in a Novel Mouse Model of HIV-Associated Sensory Neuropathy.Mol Neurobiol. 2023 May;60(5):2954-2968. doi: 10.1007/s12035-023-03244-8. Epub 2023 Feb 9. Mol Neurobiol. 2023. PMID: 36754911
-
Insights into Vincristine-Induced Peripheral Neuropathy in Aged Rats: Wallerian Degeneration, Oxidative Damage, and Alterations in ATPase Enzymes.ACS Chem Neurosci. 2024 Nov 6;15(21):3954-3969. doi: 10.1021/acschemneuro.4c00342. Epub 2024 Aug 29. ACS Chem Neurosci. 2024. PMID: 39207203 Free PMC article.
-
An adolescent rat model of vincristine-induced peripheral neuropathy.Neurobiol Pain. 2021 Nov 11;10:100077. doi: 10.1016/j.ynpai.2021.100077. eCollection 2021 Aug-Dec. Neurobiol Pain. 2021. PMID: 34841128 Free PMC article.
-
Monoclonal Antibody Targeting the Matrix Metalloproteinase 9 Prevents and Reverses Paclitaxel-Induced Peripheral Neuropathy in Mice.J Pain. 2019 May;20(5):515-527. doi: 10.1016/j.jpain.2018.11.003. Epub 2018 Nov 22. J Pain. 2019. PMID: 30471427 Free PMC article.
References
-
- Aley KO, Reichling DB, Levine JD. Vincristine hyperalgesia in the rat: a model of painful vincristine neuropathy in humans. Neuroscience. 1996;73(1):259–265. - PubMed
-
- Asahina A, Hosoi J, Grabbe S, Granstein RD. Modulation of Langerhans cell function by epidermal nerves. J Allergy Clin Immunol. 1995;96(6, Supplement):1178–1182. - PubMed
-
- Authier N, Gillet J-P, Fialip J, Eschalier A, Coudore F. A New Animal Model of Vincristine-Induced Nociceptive Peripheral Neuropathy. NeuroToxicology. 2003;24(6):797–805. - PubMed
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources