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Early life vincristine exposure evokes mechanical pain hypersensitivity in the developing rat

Schappacher, Katie A.a,b; Styczynski, Laurena; Baccei, Mark L.a,*

doi: 10.1097/j.pain.0000000000000953
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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.

Vincristine administration to rats during the early postnatal period evokes a selective increase in mechanical pain sensitivity that persists into adulthood.

aPain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA

bDepartments of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

Corresponding author. Address: Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA. E-mail address: mark.baccei@uc.edu (M. L. Baccei).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

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Received March 17, 2017

Received in revised form May 09, 2017

Accepted May 10, 2017

© 2017 International Association for the Study of Pain