Vincristine-induced allodynia in the rat

Abstract

The aims of this study were two-fold: first, to simplify the method for creating a recently described neuropathic pain model in the rat, and second, to evaluate the effects of a number of drugs with analgesic or antihyperalgesic properties, in this model. Continuous intravenous vincristine infusion (1-100 microg kg(-1) day (-1)) for 14 days resulted in a dose dependent tactile allodynia (as measured by von Frey filaments) by 7 days at doses between 30 - 100 microg kg(-1) day (-1), with a hindlimb motor deficit observed at doses greater than 50 microg kg(-1) day (-1). No thermal hyperalgesia was observed. Systemic morphine, lidocaine, mexiletine and pregabalin (given intraperitoneally) produced significant reduction of the allodynia, while tetrodotoxin was without effect. Continuous intravenous infusion of vincristine in rats thus provides a reliable model of chemotherapy induced neuropathy which may be used in defining the mechanism and pharmacology of this clinically relevant condition.

Animal Models of Chemotherapy-Evoked Painful Peripheral Neuropathies

“…Single injection of morphine, anticonvulsant drugs (lamotrigine, ethosuximide, carbamazepin, pregabalin), but also venlafaxine (antidepressant), mexiletine and lidocaine (Na channel blockers), clonidine (␣ 1 agonist), dextrometorphan (glutamate receptor blockers), and acetaminophen totally reversed vincristine-induced tactile allodynia. 18,19,[53][54][55] On the other hand, some nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., aspirin, ibuprofen, celecoxib) and also desipramine (tricyclic antidepressant) did not present a curative effect on this nociceptive symptom after a single injection. 19 According to specific studies on gabapentin, 56 it seems to be effective only after repeated injection on vincristine-induced mechanical allodynia/hyperalgesia.…”

Paclitaxel- and vincristine-evoked painful peripheral neuropathies: Loss of epidermal innervation and activation of Langerhans cells

“…Animal experiments using relatively high systemic doses of paclitaxel, or injections of paclitaxel directly into a peripheral nerve, have provided evidence of axonal degeneration, but in these experiments, the animals are hypoesthetic or anesthetic (e.g., Cliffer et al, 1998;Lauria et al, 2005a). In contrast, relatively low systemic doses of paclitaxel and vincristine produce signs of pain hypersensitivity, including allodynia and hyper-algesia (Aley et al, 1996;Authier et al, 1999Authier et al, , 2000Authier et al, , 2003Polomano et al, 2001;Nozaki-Taguchi et al, 2001;Siau and Bennett, 2006). Light-and electron microscopic studies of peripheral nerves from rats with low-dose paclitaxel-and vincristine-evoked painful peripheral neuropathies have failed to find any axonal degeneration in peripheral nerve (Tanner et al, 1998a;Polomano et al, 2001;Topp et al, 2000;.…”

Animal Models of Cancer Pain

“…65 whereas cold allodynia occurred 1 wk after the infusion. 99 This mechanical hyperalgesia could be attenuated by morphine or lidocaine administration 126 but not by the μ opioid agonist DAM-GO. 1 Because vincristine treatment produces different results in different experimental paradigms-hyperalgesia, hypoalgesia and allodynia, its mechanisms of action remain to be identified.…”

“…166 Continuous infusion of vincristine led to dose-dependent mechanical allodynia but not thermal hyperalgesia. 126 Mechanical allodynia started after 1 wk of vincristine infusion and returned to the baseline values by 4 wk, This study was conducted by targeting DRG axons expressing TRPV1. The hypothesis behind this investigation was that selectively ablating the DRG neurons expressing TRPV1 receptors would control chronic bone cancer pain, while leaving other sensory functions intact.…”