ABSTRACT
Background and Objective: Metformin (MET) has been used as an antidiabetic agent for type II diabetes. At the same time, recent researches have shown that the clinical improvement of MET is useful for nerve damage. In this study, we investigated the analgesic effect of MET in paclitaxel (PAC)-induced neuropathic pain. Materials and Methods: Forty-two adult, female rats, Wistar strain weighing 220 ± 10 g were randomly divided into 5 experimental groups. PAC was intraperitoneally (IP) administered (2.0 mg/kg) for 4 groups every other day (0, 2, 4, and 6 days). By the 30th day, MET (100, 200, and 400 mg/kg) was administered to 4 groups. Before and after treatment, basal pain threshold values were measured with Randall–Selitto analgesiometer test. At the end of experiment, pathological values were measured in selected regions including brain (motor cortex, M1), spinal cord (L4-L5), sciatic nerve, and muscle. Results: According to our results, PAC-induced neuropathic pain reached to highest level at 14th day. Four hundred milligram/kilogram concentration of MET remarkably decreased PAC-induced neuropathic pain. On the other hand, pathologic features have shown that PAC had significant pathological change in the brain and spinal cord while in the peripheral nerves and muscles had not shown any pathological change. Conclusion: The pathological results of the current study for the first time demonstrated that MET beside of its antidiabetic effects reversed neuropathic pain induced by PAC. Consequently, this research can be promising for cancer patients that suffering from neuropathic pain induced by anticancer drugs.
ABSTRACT
Different neuronal cells are found in olfactory bulb, cortex and cerebellum regions. Olfactory regulates complex behaviors, cerebellum has a great role in body balance and cortex mainly coordinate complex motor and sensory behaviors. The anesthetic is given to all patients (from birth to death) who undergo surgery. Midazolam is GABA agonist and used as an anesthesia. Glutamate an excitatory neurotransmitter can reach toxic levels in traumatic brain injury to cause schizophrenia and behavior disorders. In this study, we obtained 3 different olfactories, cortex and cerebellum cell culture. Glutamate 5-10 mM was added to all culture dishes except the negative control group. Midazolam was added in 4 different doses for 24th and then evaluation was done by MTT, TAC (Total antioxidant capacity), TOS (Total oxidant status) and flow cytometry (Annxin V-apoptosis marker). Our results show that although ketamine is NMDA antagonist there is an increased toxicity level of glutamate and reduce cell viability.