Assessment Of Analgesic Activity Of Nelumbo Nucifera Fruit Ethanol Extract

Objective: Utilization of herbal remedies rich in flavonoids and vitamins have increased significantly these days to treat various disorders, thus existing research work encircled to appraise the analgesic effect of Nelumbo nucifera fruit (NNF) for evaluating its traditional use pharmacologically in disorders which are associated with pain and inflammation. Methods: Central analgesic activity in mice was assessed by tail flick test and the latency time i.e. the removal of tail from the stimulus was recorded. Similarly acetic acid induced writhing test was also conducted for the assessment of peripheral analgesic effect in mice and number of writhes was counted along with percent inhibition of writhes. Results: In tail flick test the peek anti-nociceptive effect at all doses of fruit was observed at 90 min. However, the percentage of tail elongation time was highest at a dose of 200 mg/kg i.e. 82% at 90 min. Number of writhes was highly significantly reduced at all doses of NNF but maximum effects were observed at dose 200 mg/kg as compared to control, indicating 48.41 % inhibition of writhes. Conclusion: NNF have exhibited strong analgesic effect in both animal models, which may be connected with the synergistic actions of flavonoids, saponins and tannins on arachidonic acid pathway inhibition. Hence NNF seems to have a great potential in disorders associated with pain but more experimental trials in this field are required to confirm these findings.

Anti-nociceptive effect of seed extract of Acacia tortilis in rodents

Background: Management of pain is a primary clinical concern for any pathology in medical field. Addiction liability of opioids and troublesome gastrointestinal side effects of NSAIDs leads to intensive research for compound with lesser side effects.The aim of the study to evaluate the anti-nociceptive activity of Acacia Tortilis Seed Extract (ATE) in experimental animals.Methods: First of all, animals were randomly allocated into four groups of six animals each. In acetic acid induced writhing test model, Group I (NC) served as vehicle control received saline/Tween 80 0.1%, 10ml/kg BW orally, group II (ATE-100) and III (ATE-200) received ATE in dose of 100 and 200mg/kg BW orally respectively and group IV received the standard drug diclofenac sodium in dose of 50 mg/kg BW orally. Group I to IV were same in rest of three experimental models. One additional group of standard drugs (group V) morphine sulfate in dose of 5 mg/kg BW subcutaneously (SC) was allocated for screening method hot plate and tail flick tests. In Formalin induced paw licking test, three additional groups (group V) morphine sulfate in dose of 5mg/kg BW SC, group VI- morphine+naloxone (5mg/kg SC +2mg/kg intra-peritoneally (IP) and group VII - ATE+ naloxone (200mg/kg BW orally +2mg/kg BW IP) were also made.Results: The ATE when administered orally in dose of 100 and 200mg/ kg body weight (BW), produced significant analgesic activity (P <0.01) in acetic acid induced writhing syndrome and late phase of formalin test. In the hot plate test in mice and tail flick test in rats, ATE in same doses also showed significant analgesic activity (P <0.05) which is almost equally efficacious to standard drug diclofenac sodium (50mg/kg BW orally) but far less efficacious than morphine sulfate (5mg/kg BW subcutaneous).ATE (200mg/Kg BW orally) activity did not blocked by naloxone (2mg/kg intra-peritoneal).Conclusions: ATE possesss significant anti-nociceptive activity as evidenced in all the animal models of nociception. It might exert its effect through the peripheral mechanism of analgesic action possibly by interference in biosynthesis, release and/or action of prostaglandins and leukotrienes.

Antinociceptive and anti-inflammatory effects of Lantana camara L. extract in mice / Efeitos antinociceptivos do extrato de Lantana camara L. em camundongos

ABSTRACT: he Lantana camara L. belongs to the family Verbenaceae, which contains several active compounds in leaves and roots and which are reported to have medicinal and insecticidal properties. Studies of plants within the same family show the existence of anti-inflammatory activity in paw edema induced by carrageenan, serotonin and histamine and analgesic activity in the acetic acid writhing and tail-flick tests. The present study investigated whether the L. camara extract (ACE) also exerts these effects. The ACE toxicity was studied in male mice, and the percentage of mortality recorded 7 days after treatment was assessed. The ACE was evaluated as an antinociceptive agent in the hot plate, tail-flick and acetic acid writhing tests at a nontoxic dose of 1.0 g/Kg. The results showed that 1.5 g/Kg of ACE was not able to cause death, and doses of 3.0 and 4.0 g/Kg caused 50% and 60% death, respectively, in male mice. In all of the antinociceptive tests, 1 g/Kg of ACE markedly reduced responses to pain. Our findings suggest that ACE may have active anti-inflammatory and antinociceptive properties in much smaller doses than toxic.

RESUMO: Lantana camara L. pertence à família Verbenaceae, a qual contem muitos princípios ativos em suas folhas e raízes com propriedade medicinais e inseticidas. Estudos com plantas da mesma família mostram a existência de propriedades antinflamatórias no modelo de edema de pata induzido pela carragenina, serotonina e histamina, além da atividade analgésica nos testes de contorção induzida pelo ácido acético e da retirada da cauda por estímulo térmico. O presente trabalho investigou os efeitos tóxicos e antinociceptivos do extrato de L. camara (ACE) em camundongos. Para tanto, investigou-se a porcentagem de mortes em 7 dias após a administração de diferentes doses do extrato. Avaliou-se também os efeitos antinociceptivos do ACE pelos testes da placa quente, estimulação térmica da cauda e contorções abdominais induzidas pelo ácido acético com a dose não-tóxica [1,0 g/Kg]. Os resultados mostraram que 1,5 g/Kg do ACE não causou mortalidade, enquanto que 3,0 e 4,0 g/Kg promoveram 50 e 60% de mortalidade, respectivamente. Em todos os testes antinociceptivos, a dose de 1,0 g/Kg do ACE reduziu a resposta à dor. Os presentes resultados indicam que o ACE apresenta propriedades antinflamatórias e analgésicas em doses muito menores que a tóxica.

Evaluation of antidepressant and analgesic activity of tapentadol with mirtazapine: an experimental study.

Background: Data comparing tapentadol with an antidepressant is limited. A comparison of tapentadol with mirtazapine at different dose has not been performed, the other antidepressant in the same therapeutic class with a significant market share, has been undertaken. In the absence of relevant data to assess the place that tapentadol should occupy in the therapeutic arsenal, indirect comparisons are the most rigorous way to go. We conducted a study evaluate antidepressant and analgesic activity of tapentadol with mirtazapine at different doses in Swiss albino mice. Methods: Tapentadol was administered at 10, 20 and 40 mg/kg (i.p) once daily for 14 days to swiss albino mice of either sex. The immobility period for antidepressant activity of mice were recorded in forced swim test and reaction time for analgesic activity of mice were recorded in tail flick test of the control and drug treated group. The antidepressant and analgesic activity of tapentadol (10, 20, 40 mg/kg i.p) was compared with that of mirtazapine (3, 5, 7 mg/kg i.p), administered for 14 days. Results: Tapentadol produced better antidepressant at (20, 40 mg/kg), but less at 10 mg/kg and significant analgesic activity at all the three doses, as indicated by reduction in immobility times and increase in reaction time as compared to control. Mirtazapine produced no antinociceptive activity at 3 mg/kg, but significant at 5, 7 mg/kg and showed better antidepressant activity at all the three doses in mice. The result of this study indicates the better analgesic activity of tapentadol at all the doses and least antidepressant activity at 10 mg/kg, as compared to mirtazapine which has shown better antidepressant activity at all the three doses but no analgesic activity at 3 mg/kg. Conclusion: It can be concluded that tapentadol is a better drug in case of depression associated with pain compared to mirtazapine in mice.

Potentiation of morphine analgesia with co-administration of Nimodipine in Rat, Tail-Flick test study: Implication in the treatment of chronic pain.

Background: Opioids like morphine produce side effects ranging from nausea and vomiting, pruritus, over sedation, dizziness and urinary retention to respiratory depression. Particularly, on chronic administration, it leads to development of tolerance. Combining opioids with certain other drugs (adjuvant analgesics) like ketamine, which is an N-methyl-D-aspartate (NMDA) receptor antagonist, not only increases the analgesia, but also reduces the dose of opioids. Previous research done in our laboratory and outside suggests that nimodipine, an L-type calcium channel blocker (L-CCBs), could be one such adjuvant drug. Aims & Objective: To study of morphine-induced analgesia and the development of morphine tolerance & effect of nimodipine on morphine-induced analgesia and tolerance. Materials and Methods: The experimental work was divided into 2 parts: (i) Part I – Study of morphine induced analgesia and the development of morphine tolerance; and (ii) Part II – Study the effect of nimodipine on morphine-induced analgesia and tolerance. Adult Wistar rats (n=24) received either normal saline, L-CCB (Nimodipine), Morphine or both drugs (Morphine + Nimodipe). Tail-Flick test was done after 40 minutes of injection. To compare the control with treated groups, statistical analysis of the values of Tail-flick latency was done by Kruskal Wallis one way ANOVA, followed by "Tukey's Multiple Comparison Test” (multiple range 't' test) (p<0.05 was taken to be significant). Results: The values of tail-flick latency were almost equal to baseline values for group I, throughout the experiment, while for group II, values of tail-flick latency were almost equal to the cut off time (9.15 ± 1.762), at day 1, but gradually the values decreases over the time period of experiment and at the end of experiment, tail-flick values reaches to base line value. Tail-flick latency for nimodipine was the same as for saline. Values of tail-flick latency for group IV were higher in comparison with group II. Conclusion: The present study indicates that antagonist of L-VGCCs, particularly nimodipine, may enhance the analgesic potency of opioids like morphine and also delayed the development of opioid tolerance.

Antinociceptive Effect of Ethanolic Extract of Hybanthus enneaspermus Leaf in Rats.

Aims: To test the hypothesis that Hybanthus enneaspermus leaf has an antinociceptive effect. Methodology: Seventy-two male rats were randomly divided in a blinded fashion into 4 groups each for the tail immersion test (n=12 per group) and formalin test (n=6 per group). Group 1 (control) received 0.6 ml of distilled water. Group 2 received 100 mg/kg of acetaminophen (paracetamol). Group 3 and 4 received 500 mg/kg and 1000 mg/kg of ethanolic extract of Hybanthus enneaspermus leaf (EEHE) respectively. Results: In the formalin test, oral administration of 500 mg/kg and 1000 mg/kg EEHE caused inhibitions of 62.48% and 72% in the early phase and 70.54% and 78.63% in the late phase respectively. The 1000 mg/kg dose significantly reduced the paw licking time when compared to the standard drug (acetaminophen) in the formalin test. The 500 mg/kg and 1000 mg/kg doses significantly increased the tail flick latency in a manner comparable to acetaminophen. Conclusion: This study showed that the leaf has an anti-nociceptive effect.

Preparation and analgesic effect of α-cobrotoxin-loaded poly(lactide-co-glycolide) microspheres / 中国药理学通报

Aim To study the preparation of α-cobro-toxin-loaded poly ( lactide-co-glycolide ) microspheres and their analgesic effect. Method The microspheres were prepared by modified water-in-oil-in-oil ( w/o/o ) emulsion solvent evaporation method. A tail flick assay was used to evaluate the analgesic activity of the micro-spheres after nasal administration. Result The micro-spheres with high entrapment efficiency ( >80%) and average diameter of about 25 μm could be prepared by modified water-in-oil-in-oil ( w/o/o ) emulsion solvent evaporation method. A tail flick assy showed the evi-dence for their analgesic effect. Conclusion When Chinese cobraneurotoxin is loaded into microsphere and then the microsphere is administered through nasal cav-ity, its analgesic effect is enhanced significantly.

Exercise alleviates hypoalgesia and increases the level of calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats

OBJECTIVE: The aim of this study was to evaluate the effects of treadmill training on nociceptive sensitivity and immunoreactivity to calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats. METHODS: Male Wistar rats were divided into three groups: control, diabetic and trained diabetic. Treadmill training was performed for 8 weeks. The blood glucose concentrations and body weight were evaluated 48 h after diabetes induction and every 30 days thereafter. The nociceptive sensitivity was evaluated using the tail-flick apparatus. The animals were then transcardially perfused, and the spinal cords were post-fixed, cryoprotected and sectioned in a cryostat. Immunohistochemistry for calcitonin gene-related peptide analysis was performed on the dorsal horn of the spinal cord. RESULTS: The nociceptive sensitivity analysis revealed that, compared with the control and trained diabetic animals, the latency to tail deflection on the apparatus was longer for the diabetic animals. Optical densitometry demonstrated decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord in diabetic animals, which was reversed by treadmill training. CONCLUSION: We concluded that treadmill training can alleviate nociceptive hypoalgesia and reverse decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord of diabetic animals without pharmacological treatment.

The analgesic and anti-inflammatory activities of the hydroalcholic extract of "Shirishadi compound" in animal model.

The main objective of the present investigation is to evaluate the anti-inflammatory & analgesic activity of ethanolic extract of Shirishadi polyherbal compound on rats. Shirishadi compound consist of three herbal drugs namely- Shirisha (Albizzia lebbeck), Nagarmotha (Cyprus rotandus) & Kantakari (Solanum xanthocarpum).In Ayurveda (ancient Indian system of medicine) all these herbs alone or in combination with other herbs are commonly used in the managmant of bronchial asthma. In the carrageenan-induced rat paw edema test for acute inflammation, the extract of Shirishadi compound in doses of 50mg, 200 mg and 500 mg/kg body weight showed 77% and 79% and 81% inhibition of edema, respectively, at the end of 4h which is comparable to that of standard ( endomethacin) i.e. 92%. In the acetic acid induced writhing test the extract of Shirishadi compound ( 200 and 500 mg/kg body weight) showed a significant (p<0.001) reduction in the number of writhes with 65.6% and 70.9% of inhibition, respectively. In radiant heat tail-flick test the crude extract produced 58.1% (p<0.001) and 61.1% (p<0.001) elongation of tail flicking time 30 minutes after oral doses of 200 and 500 mg/kg body weight respectively . After 60 minutes the extract showed 56.3% (p<0.001) and 59% (p<0.001) elongation of tail flicking time. Experimental results showed that Shirishadi compound has persuasive anti-inflammmatory property along with significant analgesic activity.

Antinociceptive activity of methanolic extract of leaves of Achyranthes aspera Linn. (Amaranthaceae) in animal models of nociception.

Antinociceptive activity of methanolic extract of leaves of A. aspera was studied by peripheral/non-narcotic model of nociception like acetic acid induced writhing syndrome test and central/narcotic models like hot plate and tail flick tests. The methanolic extract of the plant, administered orally (@ 300, 600 and 900 mg/kg, body weight) and the standard drug (piroxicam; 10 mg/kg body weight, po) produced significant analgesic activity in acetic acid induced writhing syndrome as compared to the vehicle treated control group. In the hot plate analgesic test, in A. aspera at the above doses and the standard drug treated group (morphine sulphate @ 1.5 mg/kg, ip), the duration of reaction time (sec) increased dose dependently and significantly compared to the control group. In the tail flick test, the plant extract produced dose dependant increase in reaction time which was significantly higher in the test and standard group compared to the control group. The plant possesses significant antinociceptive property as evidenced in all the animal models of nociception. It might possibly exert its effect through diverse mechanism that may involve both central and peripheral pathways. The preliminary phytochemical investigation revealed the presence of steroids, alkaloids and triterpene in the methanolic extract of leaves of A. aspera which may be responsible for its antinociceptive activity.

Intrathecal lamotrigine blocks and reverses antinociceptive morphine tolerance in rats / 대한마취과학회지

BACKGROUND: Chronic administration of morphine leads to the development of tolerance. We investigated the effects of intrathecal lamotrigine on the spinal morphine tolerance in rats that are undergoing tail flick tests. METHODS: Sprague-Dawley rats were given intrathecal injections of saline 10 microl, lamotrigine 300 microg, morphine 15 microg or lamotrigine plus morphine combinations for 7 days (lamotrigine was given for days 1-7, days 1-3 or days 5-7). The acute and chronic nociceptive sensitivities were assessed using a tail flick test in which the distal 5 cm of the tail was dipped into warm water before and 30 minutes after the drug injection. With successive injections of morphine on day 8, a cumulative antinociceptive dose-response curve was constructed and the 50% effective dose (ED50) was calculated for each study group. RESULTS: The coinjection group of lamotrigine with morphine blocked the development of tolerance, as was shown by the preservation of morphine antinociception over 7 days and the concomitant decrease in the ED50 values on day 8, as compared with the morphine-alone group. Coinjection of lamotrigine blocked the development of morphine tolerance, as shown by the preservation of morphine antinociception over 7 days and the concomitant decrease in the ED50 values on day 8, as compared with the morphine-alone group. CONCLUSIONS: This study suggests that lamotrigine augments the antinociceptive action of both acute and chronic morphine therapy, and it also attenuates the antinociceptive morphine tolerance in rats.

Effect of intrathecal oxcarbazepine on rat tail flick test-determined morphine tolerance / 대한마취과학회지

BACKGROUND: Repeated administration of morphine leads to characteristic tolerance. We tested the effects of intrathecal oxcarbazepine (OXC) on spinal morphine tolerance in rats using the tail flick test. METHODS: Sprague-Dawley rats received intrathecal injections of 10 microliter saline alone, or 10 microliter of solutions containing 100 microgram OXC, 15 microgram morphine, or OXC + morphine for 7 days. Different groups of rats received OXC on days 1-7, 1-3, or 5-7. The tail-flick assay was used to measure acute and chronic nociception. The nociceptive stimulus consisted of dipping the distal 5 cm of the tail into warm water before and 30 min after drug injection. On day 8, an antinociceptive dose-response curve was plotted, and the 50% effective dose for morphine (given alone) was determined for all groups. RESULTS: Morphine or OXC both produced acute antinociception; OXC + morphine resulted in a significantly larger response than obtained with morphine alone. Morphine tolerance was produced by intrathecal injection of morphine over 7 days. Co-administration of morphine and OXC completely blocked morphine tolerance, but tolerance developed when OXC injection was stopped, and morphine potency was partially restored by co-administration of OXC in tolerant rats. CONCLUSIONS: The antinociceptive effect of both acute and chronic morphine therapy is increased with intrathecal OXC, and antinociceptive morphine tolerance is attenuated in rats.

Influence of intrathecal injection of p-MPPF on the analgesic effects of isoflurane / 中国药理学通报

0. 05) . Compared with Iso analgesic group ( Iso group) ,the TFL or HPPT of co-administration groups ( Iso + M6 group,Iso + M3 group) shortened ( P 0. 05) . Conclusion These findings suggest that the surface analgesic effects of Iso are closely related to the excited 5-HT1A receptor in the spinal cord of mice.

A Role of Substancy P Containing Primary Afferent Fibers for The Electro-acupuncture Analgesia / 全日本鍼灸学会雑誌

The effects of local application of capsaicin (CAP) to peripheral nerves on electroacupuncture (EA) analgesia were behaviorally examined in the rats. Pain threshold, datermined by using a hot-plate and tail-flick methods, increased to 160-180% of the control value after EA, which was applied to the acupuncture points between LI-11 and LI-12 of the rat forepaw. After the local application of CAP to the radial, ulner and median nerves of the animal's right forepaw, the EA, applied to the treated forepaw, did not significantly change the pain threshold. In the same animals, the EA applied to the untreated side increased the threshold as high as that before the CAP treatment. This indecates that the EA became ineffective on the CAP treated side, this ineffectiveness of the EA cont inued until at last 15 days in the case of the single CAP treatment for 15min, on the peripheral nerves. The substance P (SP) concentration in the spinal dolsal horn (C5-7) of these animals, which was measured by radioimmunoassay, was about 40% lower in the CAP treated side than in the untreated side.<br>These results suggest that SP-containing primary afferents, of which nerve conduction was probably blocked by treatment whth CAP, convey information for EA analgesia.