Proceedings of The Physiological Society

Physiology 2014 (London, UK) (2014) Proc Physiol Soc 31, PCB070

Poster Communications

Effect of Duloxetine on peripheral neuropathy induced by Vincristine in rats

S. M. Greish1, N. M. Abogresha1, S. A. Zaiton2

1. Physiology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt. 2. Pharmacology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.

Background: Neuropathic pain is a common and severely disabling state that affects millions of people worldwide (Makoto et al 2005). Vincristine-induced peripheral neuropathy models showed mixed sensory motor neuropathy (Higuera E and Luo Z, 2004). Duloxetine is the first Food and Drug Administration-approved prescription drug for the management of diabetic peripheral neuropathic pain (Wernicke et al., 2006). Aim: The present study aimed to explore the dose-dependent effect of Duloxetine on Vincristine-induced neuropathy in rats. Methods: Fifty albino Sprague Dawley rats were divided into 5 groups, 10 rats each, as following: Group 1: Saline group. Group 2: Vincristine-treated group (0.3 mg/kg/day, 3 doses) by I.P. injection to induce peripheral neuropathy (Siau and Bennett, 2006). Group 3, 4 and 5: injected with Vincristine then treated with Duloxetine daily by oral gavage at different doses (10, 20 and 30 mg/kg/day). After 6 weeks open field test for behavioural parameters (Abogresha N et al., 2013), nociceptive response was done through three tests (hot plate, tail immersion in hot and cold water) then the latency of the reaction was calculated (Bannon A and Malmberg A 2007, Ghule B et al, 2007). Animals were euthanized by inhalation of an overdose of ether; nerve conduction velocity (NCV) and histopathological examination was done for the sciatic nerve. Immunohistochemical assessment with anti-CD11b was done as a microglial marker in the spinal cord. Results: Hotplate and Tail immersion results showed significant hyperalgesia in the Vin-treated group when compared with saline (P<0.05). Moreover, a significant difference in latencies was observed between Vin-treated rats and Duloxetine 20, 30 mg/kg treated groups (P<0.05). There is a significant decrease in NCV recorded from Vin-treated group when compared to Saline group (49.66 ± 4.58 and77.92 ± 5.8P mm/s; P<0.05). NCV was significantly increased in treated groups at 20 or 30 mg/kg when compared to Vin-treated group (81.53 ± 4.06, 79.56 ± 2.35 and 49.66 ± 4.58 mm/s; P<0.05). Vin-treated group showed a decrease in ambulation, activity factor and mobility duration compared to the saline group. Treatment with Duloxetine 20, 30mg/kg improved these parameters as compared to Vin-treated group (P<0.05). The Two doses of Duloxetine (20 and 30 mg/kg) significantly ameliorated the widespread histopathological alterations which appeared apparent in the Vin-treated group (fig 1). The two doses of Duloxetine (20 or 30 mg/kg) significantly decreased the expression of microglia marker (CD11b) when compared to Vin-treated group (P<0.05). Only in Vin-treated group, there is a significant increase in the expression of microglial marker when compared to other groups (fig 2).Conclusion: Duloxetine in high doses can reverse the painful neuropathy induced by Vincristine. Spinal Microglia involvement may be considered as an assisting mechanism.Statistical analysis:The difference of mean values assessed by using ANOVA followed by Bonferroni'stest.

Where applicable, experiments conform with Society ethical requirements