Antinociceptive Effect of Memantine and Morphine on Vincristine-induced Peripheral Neuropathy in Rats

Abstract

BackgroundVincristine-induced peripheral neuropathy is a major dose limiting side effect and thus effective therapeutic strategy is required. In this study, we investigated the antinociceptive effect of memantine and morphine on a vincristine-induced peripheral neuropathy model in rats.MethodsMale Sprague-Dawley rats weighing 220-240 g were used in all experiments. Rats subsequently received daily intraperitoneal injections of either vincristine sulfate (0.1 ml/kg/day) or saline (0.1 ml/kg/day) over 12 days, immediately following behavioral testing. For assessment of mechanical allodynia, mechanical stimuli using von Frey filament was applied to the paw to measure withdrawal threshold. The effects of N-methyl-D-aspartate receptors antagonist (memantine; 2.5, 5, 10 mg/kg intraperitoneal), opioid agonist (morphine; 2.5, 5, 10 mg/kg intraperitoneal) and vehicle (saline) on vicristine-induced neuropathy were evaluated.ResultsMechanical allodynia developed over the course of ten daily injections of vincristine relative to groups receiving saline at the same time. Morphine abolished the reduction in paw withdrawal threshold compared to vehicle and produced dose-responsiveness. Only the highest dose of memantine (10 mg/kg) was able to increase paw withdrawal threshold compared to vehicle.ConclusionsSystemic morphine and memantine have an antinociceptive effect on the vincristine-induced peripheral neuropathy model in rats. These results suggest morphine and memantine may be an alternative approach for the treatment of vincristine-induced peripheral neuropathic pain.

Antinociceptive effect of Matricaria chamomilla on vincristine-induced peripheral neuropathy in mice

“…In this study, systemic morphine significantly Nouri et al 27 decreased pain responses in both phases of formalin in vincristine induced neuropathic test of 10 mg/kg, that is, similar results have been published with other models of neuropathic pain (Bulka et al, 2002;Erichsen et al, 2005;Park et al, 2010). In contrast, another study found opioid agonists, such as morphine (5 mg/kg, i.p.)…”

“…Better understanding of the underlying mechanisms is critical to allow identification of therapeutic targets, especially if these drugs produce their neurotoxic effects by mechanisms different from those by which they kill tumor cells (Park et al, 2010). Thus, although it is generally held that the therapeutic effects of vincristine is preventing tumor cell replication through alteration of cytoskeletal structure and disorientation of microtubules (Himes et al, 1976;Owellen et al, 1976), the mechanism by which they produce painful peripheral neuropathy, a major doselimiting side effect for this class of therapeutic agents, is not well understood (Park et al, 2010).…”

“…The volume was adjusted to 1 ml/kg for intravenous and 5 ml/paw for intradermal administration. Dose selection of each agent was based on the results of previous studies (Aley and Levine, 2002;Levine, 2004, 2006;Park et al, 2010). …”

Comparison of the Analgesic Activity of Antiparkinsonian Aminoadamantane Derivatives Amantadine and Hemantane

“…Memantine, a 1-aminoadamantane derivative and an uncompetitive NMDA receptor antagonist, had an antinociceptive effect in the vincristine-induced peripheral neuropathy model in rats at a dose of 10 mg/kg [35]. Some derivatives of 1-aminoadamantane are investigated as potential analgesic compounds because of their agonist activity at CB 2 or/and CB 1 cannabinoid receptors [36] [37].…”

Neuropathy Secondary to Chemotherapy: A Real Issue for Cancer Survivors

“…Some cases have been also described of vincristine-induced CIPN with neuropathic pain, which are very distressing and painful with very difficult treatments. The study by by Park et al (2010) investigated the antinociceptive effect of memantine and morphine on a vincristine-induced CIPN model in rats. The authors concluded that systemic morphine and memantine have an antinociceptive effect in animal models.…”