Results: 6-hr acute restraint stress caused severe anxiety like behavior, antinociception and impaired locomotor activity as compared to unstressed animals. Biochemical analyses revealed an increase in malondialdehyde, nitrites concentration, depletion of reduced glutathione and catalase activity as compared to unstressed animal brain. Five days St. John's Wort treatment in a dose of 50 mg/kg and 100 mg/kg significantly attenuated restraint stress-induced behavioral (improved locomotor activity, reduced tail flick latency and antianxiety like effect) and oxidative damage as compared to control (restraint stress).
ABSTRACT: Aim and Objectives: To study the analgesic activity of telmisartan in graded doses, in tail flick method and acetic acid induced writhing method in rats and mice respectively. Materials and Methods: Analgesic activity of telmisartan was evaluated in graded doses tail flick model (for central action) and acetic acid induced writhing model (for peripheral action) of analgesia. Aspirin & tramadol were used as standard drugs. Results were analyzed by one way ANOVA followed by Bonferroni’s post hoc test. Results: In tail flick method telmisartan showed dose dependent analgesic activity. The tail flick latency time increased from 0 to 60 min. The analgesic activity of telmisartan at dose of 1.5mg/kg was not statistically significant, however it was statistically significant at dose 3mg/kg and 4.5 mg/kg. At the dose of 3mg/kg; telmisartan showed highly significant activity p<0.01 at 30, 60 as well as 90 min with maximum effect at 90min, where as the most significant effect p<0.001 was observed at the dose of 4.5mg/kg at 60 and 90min. In acetic acid induced writhing method, the telmisartan possessed significant analgesic activity at all three doses (1.5mg/kg, 3mg/kg and 4.5mg/kg) with maximum activity at the dose of 4.5mg/kg. Conclusion: Telmisartan an angiotensin II AT1 receptor antagonist possess significant analgesic activity. It should be investigated further as potential treatment option for painful conditions in hypertensive patients.
The prescreened animals (reaction time: 6- 7 seconds) were divided into IV groups as described above. After administration of extract or vehicle or standard, the tail flick latency was assessed at 15, 30, 45, 60, and 120 minute by analgesiometer. The strength of current passing through naked nichrome wire was kept constant at 4 amps. The site of application of the radiant heat in the tail was maintained at 2.5 cm, measured from the root of the tail. The cut off time was fixed 15 seconds to avoid any tissue damage. [24, 25]
Anti-nociception was assessed by the tail flick latency (TFL) test using an automatic analgesiometer (Tail flick; Borj Sanat, Tehran, Iran), (Fig. 1). The TFLs were measured as the time between tail exposure to radiant heat and tail withdrawal. An intensity setting of 25 on a scale of 1 to 100 and a cut-off time of 15 sec, to prevent tissue damage, was used throughout the study. 8 The light beam was focused on
Our results showed that chronic swimming exercise increased pain threshold in tail flick test. This result is in agreement with previous studies showing altered nociceptive threshold following physical exercise. A considerable number of studies in laboratory animals and also in humans have demonstrated that exercise is associated with decreased pain perception [21, 22]. However, the precise mechanisms underlying the hypo nociceptive effect of exercise remained to be clearly understood. Probably the most widely considered mechanism which explains exercise-induced hypoalgesia is the activation of the endogenous opioid system. It has been shown that exercise of sufficient intensity and duration results in the release of peripheral and central opioid peptides, which have been associated with changes in pain rating . The results of present study are in line with previous human and animal studies showed the involvement of opioidergic system in the hypo nociceptive effect of exercise [24, 25]. However, it is important to note that plasma level of opioid peptides gives limited information about behavioral consequence . Therefore behavioral assessment of pain perception also needed to verify central or peripheral effects of opioidergic mechanism. Interestingly, we found that changes in plasma opioids level were consistent with behavioral results; tail flick latency also increased in exercised rats.
reported to occur in Djibouti, Uganda and Sudan . It is known by different vernacular names such as “Shiferaw” (Amharic), “Halako” (Gamo & Wollayita) , “Shelchada” (Konso), and “Cabbage tree” (English) . Traditionally, the leaves boiled in water, can treat and cure headache, malaria, hypertension and stomach pain . Recently, the in-vivo analgesic and anti- inflammatory activity of the crude leaf extract of the plant has been confirmed by Geremew et al. . This study aimed to further evaluate the analgesic and anti- inflammatory activities of the solvent fractions of M. ste- nopetala in Swiss albino mice models using radiant tail flick latency, acetic acid induced writhing and carrageenan induced paw edema. Radiant tail flick latency, and acetic acid induced writhing which are proven methods to test central and peripheral analgesic activity respectively, while carrageenan induced paw edema model is suitable for test- ing acute inflammatory responses. In addition to their cost effectiveness, Rodent models of pain have played a domin- ant role in the study of pain mechanisms .
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Mice were divided into four groups, six animals in each group. Group I: Distilled water (DW) 10 ml/kg,(p.o).Group II:Diclofenac sodium injection in dose of 25mg/kg (S.C).Group III:Petroleum ether Extract injection in dose of 200mg/kg (S.C).Group IV: Ethanol Extract injection in dose of 200mg/kg (S.C).Mice divided in the groups of six each, were held in position in a suitable restrainer with the tail extending out. 2-3 cm area of the tail was marked and immersed in the water bath thermo-statistically maintained at 51°C. The withdrawal time of the tail from hot water (in seconds) was noted as the reaction time or tail flick latency. The maximum cut off time for immersion was 180 seconds to avoid the injury of the tissues of tail. 0.2 ml of 0.9% NaCl solution was administered to control animals; plant extracts in doses of 300, 500 and 1000 mg/kg were given orally by intubation. The initial reading was taken immediately before administration of test and standard drugs and then 60, 90, 120,150 and 180 minutes after the administration. The criterion for analgesia was post drug latency which was greater than two times. Tail flick latency difference or mean increase in latency after drug administration was used to indicate the analgesia produced by test and standard drugs 14 .
plate test. Therefore, the magnitude of nociceptive stimulus is higher in the hot plate test than in the tail flick test. As the extract produced antinociception in all the tests, it can be inferred that the compound(s) in the extract may have both a peripheral and central effect A. aspera was shown to contain alkaloids like andrachcinine and andrachcinidine, (+)- allosedridine, (-)-8-epi-8-ethylnorlobelol and (-)-8-epihalosaline (16), and many alkaloids have been shown to possess antinociceptive effects (17). Although further work is needed, the antinociceptive activity may reside in the alkaloids.
Chemicals: (+)-Alpha-pinene, (+)-limonene, (-)-fenchone, trans-anethol and alpha-copaen were all in liquid form and each was used at the doses of 0.05, 0.1 and 0.2 ml.kg -1 , i.p. for tail-flick test. Alpha-pinene and fenchone were used at the dose of 0.2 ml.kg -1 , i.p. for rotarod test. Alpha-copaen was purchased from Fluka (Switzerland) and the others from Sigma-Aldrich (Steinheim,Germany). Morphine (10 mg.kg -1 ), given subcutaneously, was used as a standard for comparison and obtained from Galen (Istanbul, Turkey).
The analgesic activity of stem bark of Moringa oleifera carried out using acetic acid-induced writhing in mice and tail flick test in rats. The anti-inflammatory activity was evaluated using carrageenan-induced rat paw edema and cotton pellet-granuloma formation in rats. The effects of the administration of reference standard (diclofenac) were also evaluated. Two different extracts (Petroleum ether and Methanolic) of Moringa oleifera at the dose level of 100,200 and 400 mg/kg, p.o. were tested. Treatment with Methanol extract (100, 200, and 400 mg/kg, p.o.) showed significant (p<0.01) inhibition of carrageenan induced rat paw edema. Maximum inhibition was observed at 400 mg/kg dose as compared to the control , cotton pellet granuloma formation and acetic acid-induced writhing; however, pet ether and methanolic extracts (400 mg/kg, p.o.) were found to be more effective in increasing latency period in tail flick method. The results obtained indicate that Moringa oleifera has analgesic and antiinflammatory activities that supports the folk medicinal use of the plant.
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Ethyl acetate extract of heartwood of Aquilaria agallocha (EAA) (Family: Thymelaceceae) was tested for analgesic and anti-inflammatory activities using established methods and models reported in literature. Inhibition of the Acetic Acid induced abdominal constriction was observed at the doses of EAA 50 (34.51 %), 100 (55.65 %) and 200 (65.29 %) mg/kg as compared to the control group. EAA reduced the pain in the early (neurogenic) phase at doses of 50 (26.68 %), 100 (39.49 %) and 200 (59.87 % ) mg/kg and late (inflammatory) phase at doses of 50 (21.9 %), 100 (58.1 %) and 200 (80.2 % ) mg/kg of formalin induced paw licking in mice. EAA 50 (34.3 %), 100 (44.44 %) and 200 (82.68 %) mg/kg showed significant increase in latency time for thermal stimulation in tail flick test. On the anti-inflammatory front, EAA 50 (51.38 %), 100 (55.09 %), 200 (56.25 %) showed a significant decrease in edema induced by carrageenan in the third hour of the assay (edema peak) when compared to the normal control. In cotton pellet granuloma formation, EAA 50 (43.46 %), 100 (68.24 %), 200 (77.18 %) showed a significant reduction in the weight of granuloma in rats. The potential to cause ulcers by EAA (50, 100 and 200 mg/kg, p.o.) was comparatively less than that of diclofenac. In conclusion, heartwood of Aquilaria agallocha has analgesic as well as anti-inflammatory activities.
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Methods: Ninety-six male Wistar rats classified as responders were arbitrarily allocated into 16 groups of six rats each. Six groups received EA with uninsulated acupuncture needles (type I) or needles that were immersed in varnish and had the varnish circularly peeled 0.2 mm from the tip (type II), 0.2 mm at 3 mm (type III) or 5 mm (type IV) from the tip, or 0.2 mm at 5 and 1 mm from the tip (type V), or EA sham for 20 min. Five groups received injection of formalin into the acupoint bilaterally at 5 mm or 1 mm deep into ST36, 5 mm below ST36 but inserting the needle at 45° to the skin surface, or 5 mm deep into non-acupoints. The remaining groups received intraplantar injection of saline, 1% or 2.5% formalin. The analgesic effects were measured by the rat tail-flick test. Results: The bilateral stimulation of ST36 and SP6 by uninsulated or insulated needles produced analgesia in the rat tail-flick test. The stronger and longer lasting effects occurred after EA with the types I and V needles, or injection of formalin 5 mm deep into ST36. The remaining needles produced weaker and shorter lasting effects. Slow analgesic effect also occurred after formalin injection at 1 mm or 5 mm below ST36 by inserting the needle at 45° to the skin surface.
values within the same drug treated groups. The extract and Diclofenac sodium caused significant increase (P<0.01) in the percentage reaction time whilst the control and lower dose of extract (200 mg/kg) caused no change. The percentage increase in reaction time was dose dependent. At all the specified time intervals, the percentage of tail flick elongation time differed significantly (P<0.001) between the extract and Diclofenac sodium at both the doses of plant extract, being greater for Diclofenac sodium. At the peak of activity, 200mg/kg and 300mg/kg extract showed 43.66% (P<0.001) and 46.76% (P<0.001) percentages of tail flick elongation time respectively, whilst Diclofenac sodium gave 80.08% (P< 0.001) elongation of tail flicking time (Table: II). Time to reach peak activity was same (+30 min) for the extract and Diclofenac sodium.
In the current work, tail flick and hot plate tests were used to estimate sensory responses as a result of thermal stimuli. STZ-diabetic rats exhibited significantly shorter tail withdrawal latency than that observed in normal animals. In addition, STZ injection showed significant hyperalgesia appeared in the hot-plate test. Hyperalgesia induced by STZ was tested in different experimental models and was found to produce various pathophysiological symptoms (Courteix et al., 1994; Hounsom and Tomlinson, 1997; Kamei et al., 2001). This also is in parallel with other previous studies that described thermal hyperalgesia resulted when the tail of STZ-diabetic animals was exposed to noxious stimuli (Ohsawa and Kamei, 1999; Kamboj et al., 2010). This induced nociception in the current study was accompanied with increased blood glucose in STZ group. Treatment with aqueous, methanolic and ethanolic extracts of Ah decreased blood glucose level and increased tail withdrawal latency and retention time. Mechanisms of induced diabetic neuropathy are complicated and overlapped. However, hyperglycemia is considered a primary factor in pain hypersensitivity accompanies diabetes as it causes direct toxicity in the peripheral nervous system. It enhances the activity of primary afferent fibers, potentiates glutamate release and diminishes the opioidergic and GABAergic inhibitory systems activities (Nourooz-Zadeh et al., 1997). Chronic hyperglycemia also causes alteration in sensitivity of the dopaminergic receptors as well as responsiveness of the dopaminergic system due to inclusion of the enkephalinergic system (Wohaieb and Godin, 1987). It affects L-type Ca2+ channels that are directly responsible for modulation of nociception in diabetic rats (Feillet-Coudray et al., 1999). In parallel, Ah extracts enhanced locomotor activity indicating that it was protective against neuronal damage. It was noticed that all groups showed reduction in their final locomotor
The tail immersion test is considered to be selective for the drugs acting centrally like morphine. It has been reportedly established that any agent that causes a prolongation of pain latency using this test must be acting centrally 21 . In the present study, hydromethanolic leaves extract of Ficus polita exhibited significantly prolonged pain reaction time thereby suggesting a mechanism involving central pain pathways. Narcotic analgesics are known to inhibit both peripheral and central mechanism of pain, while NSAIDs inhibit only peripheral pain. The leaves extracts of Ficus polita exhibited both types of pain inhibition. The analgesic effect of the plants in both models suggests that they may be acting through the central and peripheral mechanism.
The traditional phytomedicine: Meiocarpidium lepidotum (Oliv.) Engl. & Diels (Annonaceae) has been used in Fang community to treat illness. This study was designed to verify the antinociceptive, antidepressant, anti-inflammatory and acute toxicity of Meiocarpidium lepidotum (ML) extract in rats and mice. The crude aqueous extract of plant containing triterpene was used in different studies. Phytochemical qualitative analysis was performed using classical and UV methods. The analgesic activity was assessed by employing different pain models, such as tail flick tests for central analgesia, acetic acid- induced writhing (peripheral analgesic model), carrageenan-induced hyperalgesia (inflammation model) in mice. In rats, an antidepressant activity was assessed by swimming test. Our study demonstrated that the crude aqueous extract of ML containing triterpene was not toxic, was capable of preventing nociception, inflammation and depression at a concentration of nearly 1 mg/kg of bodyweight. In mice, ML induced reduction of swelling of the edema paws. This anti-inflammatory effect is similar to the one obtained with 150 mg of acetylsalicylic acid (ASA) and 10 mg of indomethacin for 3 hours. It significantly reduces after 4 hours (p<0.001). The analgesic effect of 1 mg/kg of ML was similar to the effect of 0.1 mg/kg of morphine (Mph) in tail-flick tests (p<0.001) and that of 150 mg of ASA in acetic acid-induced writhing test. In addition, this study showed that 1 mg/kg of ML exhibited antidepressant effect similar to the one obtained with 32 mg/kg of Fluoxetine (p<0.01). To our knowledge, this is the first demonstration of the pronounced analgesic, anti-inflammatory and antidepressant effect of ML in vivo studies. This work validates the traditional use of ML in the Congo Basin forest as phytomedicine.
In the tail flick test, all the three doses, 50, 100 and 200 mg of the extract exhibited highly significant antinociceptive effects (p < 0.001) compared to the vehicle which was comparable to aspirin. However morphine showed higher level of activity than the herbal doses (Fig. 2; Table 2). The tail flick test is a spinally mediated nociceptive test commonly used to study pain mechanism (Bar L et al., 2001). In this study the extract was found to prolong the latency withdrawal time after radiant heat was directed to the tail of the test mice. Since the tail flick is a spinally mediated reflex, it is likely that C. megalocarpus extract acted via the central nervous system by blocking pain pathway at spinal level.
The procedure used was similar to that used by Alviano et al. in 2004  with slight modifications. The appa- ratus used consisted of a circulating immersion water heater. The thermostat was adjusted so that a constant temperature of 52˚C ± 2˚C was maintained in the water bath. Before treatment, the terminal 3 cm of each mouse’s tail was immersed in the water bath and the time in seconds taken to flick the tail was recorded. Only mice showing a pre-treatment reaction time less or equal to 4 seconds were selected for the study. Immediately after basal latency assessment, the three aqueous extract doses (190, 380 and 570 mg/kg p.o.), the two methanol extract doses (100 and 200 mg/kg p.o.), the four methanol extract fractions at 100 and 200 mg/kg p.o. each, the positive control morphine (10 mg/kg i.p.) or 3% 80 tween p.o. (negative control) were administered to groups of six mice and the reaction time was again measured 1 and 2 h after the treatment, except for morphine where measurement began 30 minutes after administration. Cut-off time was limited to 6 seconds for tail flick meas- urements to minimize tissue injury.
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Experimental analgesia was produced by placing the tip (last 1-2 cm) of the tail over radiant heat, 50ºC; withdrawal of the tail from the heat (flicking response) was taken as the end point. Normally a mouse withdraws its tail in 3-5 seconds. A cut- off period of 10-12 seconds was observed to prevent damage to the tail.
In tail flick method, Buprenorphine showed increase in reaction time at 15 minutes and maximum reaction time at 90 minutes. With neem root extract 200 mg/kg and 400 mg/kg there was no significant analgesic effect. But with dose 800 mg/kg showed maximum increase in reaction time at 60 minutes which was statistically significant (P < 0.05)