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
Background DPP-4 inhibitors showed analgesic and anti-inflammatory activity in human and animal-studies. DPP-4 inhibitors improved nerve function and thermal nociception in animal models. Aim of the study was to explore analgesic activity of single and multiple doses of teneligliptin 20 mg/day using hot air analgesiometer in healthy human volunteers.Methods: After IEC approval and informed consent, subjects were randomized to receive either teneligliptin 20 mg or placebo in double-blinded manner with standard breakfast. Mean pain threshold and tolerance(sec) using hot air analgesiometer were recorded at baseline and 1 hr, 2 hrs post drug on day 1, for single dose study. Subsequently drugs were administered under supervision daily for 6 days and same procedure repeated on day8 for multiple-dose study. After 2 weeks washout, subjects crossed over in period 2 to receive other formulation and same procedure repeated to determine study parameters. Fasting blood-sugar (FBS) was monitored, ADRs recorded in CRF. Statistical analysis done with SPSS20.0.Results: Twelve-healthy subjects (8 males, 4 females) with mean age 33.08±4.69 years, mean BMI 22.6±1.37kg/m2 participated. Single dose teneligliptin produced significant increase in pain threshold (35.9%) and pain tolerance (25.1%) (p<0.001) at 1hour compared to baseline. With multiple doses, pain threshold increased by 37.1% and pain tolerance by 25.4% (p<0.001) at 1hour compared to baseline. The increase in pain threshold and tolerance values at 1 and 2 hours were similar. There was no significant change in pain threshold(p=0.4135) and tolerance (p=0.4476) at baseline on day1 and day 8. Placebo showed non-significant change in study parameters. Both treatments well tolerated. FBS of volunteers within normal limits during treatment period and no hypoglycemia reported.Conclusions: Results of our study suggest that teneligliptin20mg in healthy subjects demonstrated modest analgesic activity compared to baseline and placebo. Its role in painful diabetic conditions may be further explored.
ABSTRACT
Background: Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. In spite of many advances in pain research, we are unable to deal in an effective way. The cost for new drug development is increasing day by day. Drug repurposing is an approach to look for new use in drugs that are already approved for other indications. Mexiletine is a sodium channel blockers that is being approved for treatment of arrhythmias. It is being tried in treatment of various painful conditions. The present study is to evaluate the dose-dependent analgesic activity of mexiletine with ibuprofen.Methods: The analgesic activity of mexiletine was compared at doses of 15mg/kg, 30mg/kg and 45mg/kg with the standard dose of ibuprofen at 10mg/kg in male Wistar rats in thermal model of tail flick analgesiometer.Results: At lower doses (15mg/kg) of mexiletine, analgesic activity of ibuprofen was significantly higher. At higher doses (30 mg/kg and 45 mg/kg) of mexiletine, it was observed that there is no significant difference between the analgesic activities of both drugs.Conclusions: Mexiletine demonstrated a dose-dependent analgesic activity. There was no statistically significant difference between the analgesic activities of higher doses of mexiletine when compared to ibuprofen.
ABSTRACT
Background: In the view of contradictory reporting concerning analgesic effect, it was planned to investigate the analgesic effect of ginger-juice (ZINGIBER OFFICINALE ROSCOE) on wistar albino rat. Methodology: Wistar albino rats (n=6-12) were administered ginger juice (GJ) at doses (4ml/rat, p.o) as single administration (single dose) and repeated dose over a period of 7 days. Effect of treatment with G.J single and repeated (7days) dose was assessed. Parameter used during assessment was licking of paw after placing the rate on analgesiometer heated up to 50C. Results: The single and repeated administration of GJ (4ml/rat,p.o for 7 days) did not indicate analgesic effect on hot plate model. Conclusion: administered itself did not show analgesic effect on hot plate model.