A study to evaluate efficacy of Tinospora cordifolia (Guduchi) as analgesic agent using albino wistar rats as an experimental animal model

Background: Pain is a very well-known symptom of many diseases and analgesics are used to relieve pain. The main problem with these drugs remains that of side effects. Herbal medicines are better in view of their cultural acceptability, better compatibility with human body systems and lesser incidence of side effects. Extract of Tinospora cordifolia (Guduchi) plant have been traditionally used to treat pain in traditional medicine.Methods: Commercially available preparation of T. cordifolia plant has been used as test drug (aqueous extract). Healthy albino rats of either sex, weighing between 140-200 g were selected for the study, divided into 4 groups of 6 each (control, standard, 100 mg/kg, 300 mg/kg). Central analgesic activity was assessed by tail flick model (morphine as standard drug I.P). Acetic acid 1% 10 ml/kg aqueous solution I.P. was used for abdominal writhing model. Diclofenac 150 mg/kg oral as standard drug for assessment of peripheral analgesic activity. Results were analysed using SPSS version 16 and Microsoft office excel 2007.Results: T. cordifolia extract significantly increased the tail flick latency time (sec) (mean tail flick latency control, T100, T300 6.833±0.25 sec, 8.65±017 sec, 10.01±0.14 respectively) (p value control vs T100, T300 at 90 min, 120 min, 0.0573, 0.0198, 0.0198 in between group) and decreased number of abdominal writhing in comparison with the control group (p value <0.0001).Conclusions: Extract of T. cordifolia was found to possess analgesic activity and also exhibited dose and time dependant increase involving central and peripheral mechanisms. The analgesic activity of T. cordifolia found to be comparable to standard drug used.

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.

A study to evaluate the analgesic activity of Origanum vulgare in mice using tail flick method

Background: Pain is a complex experience consisting of physiological and psychological response to a noxious stimulus. Analgesics like opiates and non-steroidal anti-inflammatory drugs are commonly used for relieving pain but are associated with various unwanted side effects; therefore this study was conducted by using Origanum vulgare for their analgesic efficacy.Methods: In vivo model used was tail flick method. Origanum vulgare (84 mg/kg p.o) was administered in mice. The analgesic activity was studied by recording the reaction time after administration of the drug at frequent intervals up to 3 hours. The results were analysed by ANOVA and Tukey’s test. P-value <0.05 was considered as significant. Pentazocine showed statistically prolongation in the reaction time after 30 min as compared to Origanum vulgare.Results: In tail flick method, pentazocine showed statistically significant increase in the reaction time after 30 min of administration as compared to control group. However, Origanum vulgare in a dose of 84 mg/kg showed significant increase in the reaction time after 30 min of administration as compared to control group. On comparing pentazocine and Origanum vulgare, pentazocine showed highly significant increase in the reaction time after 30 min as compared to Origanum vulgare at 84 mg/kg dose.Conclusions: From the present study, it was concluded that extract of Origanum vulgare exerted analgesic activity in both the models. However, it was less potent than pentazocine. Thus, Origanum vulgare can be used in mild to moderate painful conditions.

Evaluation of opioid sparing effect of dexmedetomidine and pregabalin using acute pain model in male wistar rats

Background: Adjuvant analgesics are added to pain management regimen to reduce opioid consumption and minimise their side effect. Newer ones like dexmedetomidine and pregabalin have not been thoroughly researched. Objectives of the study to study the opioid sparing effect of dexmedetomidine and pregabalin using tail flick and hot plate method in male wistar rats.Methods: Forty two rats were grouped into seven groups with six in each group. Analgesic activity was tested using tail flick, where in the reaction time to flick its tail on a heated surface was noted. In the hot plate method, the reaction time to withdraw or lick the paws when placed on heated surface was noted.Results: The reaction time to flick its tail was prolonged with dexmedetomidine and pregabalin when combined with opioids even in sub therapeutic doses.Conclusion: Adjuncts like dexmedetomidine and pregabalin can be very useful in mutimodal pain management and also to reduce the opioid consumption.

Dose-dependent analgesic activity of mexiletine on thermally induced pain in rats

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.

Effect of ibudilast-microinjected into nucleus accumbens on appendix pain threshold in morphine-addicted rats / 实用肿瘤学杂志

Objective The aim of this study was to investigate the effect of microinjection ibudilast on the appendix pain threshold in nucleus accumbens(NAC)of morphine-addicted rats. Methods Normal rats and morphine-addicted rats were injec-ted with ibudilast(5 μg/2 μL)or saline(2 μL)into NAC through glass microelectrode. The tail-flick period(TFL)was used as an in-dicator to observe the thermal pain threshold before and after ibuilast injection. Results After injected ibudilast 5 μg into the NAC of normal rats and morphine-added rats,the TFL was prolonged compared with that before injection,and the TFL prolongation of mor-phine-addicted rats was more significant than that of normal rats. There was no significant change in TFL after 2 μL of saline was in-jected into the NAC of normal rats and morphine-addicted rats. Conclusion Microinjection of ibudilast into NAC of normal rats and morphine-added rats can cause analgesic effect,and the analgesic effect of morphine-addicted rats is more significant.

Evaluation of analgesic activity of sodium valproate and ethanolic extract of Vitex negundo in experimental analgesic models in wistar rats

Background: NSAIDs and opioids are commonly prescribed medications to relieve pain of multiple aetiologies with no effect on the level of consciousness of the patient. They interfere with the mode of transmission of the pain message. A widely prescribed antiepileptic drug, sodium valproate has been used in various non-epileptic conditions like migraine prophylaxis and in the treatment of bipolar disorder because of the multiple mechanisms by which it acts. Vitex negundo has been investigated for antipyretic, analgesic, anti-inflammatory, anticonvulsant, hepatoprotective and bronchial relaxant. Very few studies have been done to evaluate its analgesic activity and no study was done on analgesic activity with the combination of modern drug. The more important point to be noted is that Vitex negundo is a natural product and therefore unlikely to cause adverse effects when compared to the traditional drugs used to treat pain. The aim of the present study was to evaluate of analgesic activity of sodium valproate and docosahexaenoic in experimental analgesic models in wistar rats.Methods: For analgesic activity, a total of 36 adult Wistar albino rats were taken and divided into six groups of six rats each. Group I was control (distil water 1ml/kg), Group II received intraperitoneal injection of diclofenac sodium (10mg/kg), Group III, IV were injected intraperitoneal sodium valproate 200, 400mg/kg with distil water respectively and Group V, VI were given sodium valproate 200, 400mg/kg (intraperitoneal) plus EEVN 400mg/kg (orally) respectively. Analgesic activity was assessed using hot plate, tail flick and acetic acid writhing models.Results: Present study revealed that sodium valproate at higher doses (400mg/kg) used either alone along with EEVN (400mg/kg) showed statistically significant analgesic activity in comparison to control in various experimental models for assessing pain.Conclusions: Combination of sodium valproate along with EEVN has shown promising analgesic activity.

Analgesic activity of allopurinol and febuxostat in experimental animals

Background: Currently, two classes of analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics are used to manage pain in different clinical situations. Chronic uses of these drugs have various adverse effects like gastric ulceration/bleeding, analgesic nephropathy and respiratory depression, physical dependence, addiction, respectively. Xanthine oxidase inhibitors, used for chronic gout, might have a role in alleviation of pain, as per literature survey. Hence, the present study was carried out to evaluate the potential analgesic activity of allopurinol and febuxostat in different experimental models.Methods: The analgesic activity of allopurinol and febuxostat was assessed by employing two different experimental pain models-tail flick latency model in rats for central analgesia and acetic acid induced writhing model in mice for peripheral analgesia and was compared with tramadol and aspirin.Results: Allopurinol and febuxostat produced significant central and peripheral analgesic effects as is evident from increase in reaction time in tail flick test and inhibition in number of writhes in acetic acid induced writhing test.Conclusions: The results of the present study demonstrate marked analgesic effect of allopurinol and febuxostat.

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.

Evaluation of Antinociceptive Activity of Methanol Extract from Cleome rutidosperma in Mice / 中草药·英文版

Objective Cleome rutidosperma (Capparidaceae), commonly known as “Fringed Spider Flower”, is a medicinal plant found in Southeast Asia. C. rutidosperma is used in folk medicine for diuretic, laxative, analgesic, anti-inflammatory, antipyretic, antimicrobial, anti-oxidant, hypoglycemic, and anthelmintic activities. We have evaluated the anti-nociceptive properties of methanol extract from C. rutidosperma (MECR) in vivo. Methods Thermal method (hot plate test and tail flick test) was induced to judge the anti-inflammatory effect and couple of chemical method also used (formalin induced licking test; writhing test carried by acetic acid) to evaluate analgesic effect. Both of these tests were made over animal models, like mice and rats. Two different doses (100 and 200 mg/kg) were used for each case of test, while morphine sulphate (5mg/kg, ip) was used as reference drug. Results MECR demonstrated the significantly anti-nociceptive activity in the analgesic and anti-inflammatory tests by reducing nociception in mice models (P < 0.001). In the hot-plate and tail-flick tests, MECR significantly elongated the time to response to the thermal stimuli (100 and 200 mg/kg with P < 0.05, 0.001). The remarkable increase in the latency was observed at 90 and 120 min. In acetic acid-induced writhing test and formalin induced licking test for anti-inflammatory activity, MECR at 100 and 200 mg/kg doses exhibited significant (P < 0.001) reduction of writhing and licking response. Conclusion The anti-inflammatory and analgesic effects of C. rutidosperma propose that this effect may be a result of both peripheral and central mechanisms. Further study is required to ensure the proper mechanism of action as well as the active ingredient.

Evaluation of peripheral and central analgesic activity of ethanolic extract of Clerodendrum infortunatum Linn. in experimental animals.

Background: Clerodendrum infortunatum Linn. (Verbenaceae) is an important and widely used medicinal plant. Though variously used in Ayurveda, Unani, and Homeopathy system of medicine in the case of ailments such as diarrhoea, skin disorders, venereal and scrofulous complaints, wounds, post-natal complications, as anti-helminthic, and external applications on tumors, the plant needs thorough investigation for its specific medicinal activity. This study evaluates both the central and peripheral analgesic effect of the ethanolic extract of the leaves of C. infortunatum Linn. (EECI) in the experimental animals. Methods: Acute toxicity test was done following the Organization of Economic Cooperation and Development guidelines. EECI (100 mg/kg, 200 mg/kg, and 400 mg/kg body weight [b.w.] p.o) was evaluated for central analgesic activity by the tail flick method and peripheral analgesic activity by the acetic acid (0.7%) induced writhing test, respectively. Using aspirin (300 mg/kg b.w. and 100 mg/kg b.w.) as the standard drug. Results: EECI significantly decreased the number of writhing in writhing test at all the doses (p<0.01) and increased the reaction time in tail-flick method (p<0.01) at all the doses. EECI in the dosage of 400 mg/kg b.w. produced effects which was comparable with that of the standard drug aspirin (p<0.001) in writhing test (p<0.001) and tail flick method (p<0.001). Conclusion: The study showed significant central and peripheral analgesic activity of EECI which may be attributed to the inhibition of prostaglandin synthesis, phospholipase A2, and tumor necrosis factor alpha. C. infortunatum Linn. as a commercial source of analgesic drug should be subjected to further research.

Tiopental altera a resposta nociceptiva de ratos jovens em longo prazo / Thiopental alters long term nociceptive response of young rats

The objective of this study was to evaluate the long term nociceptive response determined by use of two general anesthetics, one intravenous and the other inhalatory, in young animals. In the first experiment, the animals of 21 days of age were divided into control (saline) and thiopental (35 mg/kg, i.p.) groups. In the second experiment, rats of the same age were divided in two groups ­ halothane (2%) and control. In experiment 1, there was difference between groups ­ reduction of tail-flick latency in the group thiopental (P< 0.05). In experiment 2, there were no differences between groups or interaction between time versus group (F(1,19)=0.11 for groups, P>0.05; F(1,19)=0.032 for the interaction, P>0.05). The results obtained in this study showed that halothane did not alter the nociceptive response in young animals. However, the thiopental induced hyperalgesic response in rats. (AU)

O objetivo desse estudo foi avaliar a resposta nociceptiva a longo prazo relacionada ao uso de dois anestésicos gerais ­ um intravenoso e outro inalatório, em animais jovens. No primeiro experimento, os animais de 21 dias de idade foram divididos nos grupos controle (solução salina) e tiopental sódico (35 mg/kg, i.p.). No segundo experimento, animais de mesma idade foram divididos em dois grupos ­ halotano (2%) e controle. No Experimento 1, houve redução da latência de retirada da cauda no grupo tiopental (P<0,05). No Experimento 2, não houve diferença entre os grupos ou interação entre grupo x tempo (F(1,19)=0,11 para grupos, P>0,05; F(1,19)=0,032 para a interação, P>0,05). Os resultados obtidos nesse estudo demonstraram que o halotano não altera a resposta nociceptiva em animais jovens. Entretanto, o tiopental induziu resposta hiperalgésica nestes ratos.(AU)

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.

Analgesic and antioxidant activities of the methanolic extract of Operculina turpethum leaves in mice.

Background: Operculina turpethum Linn. (Convolvulaceae) is commonly called “Trivrit” or “India jalap” in English. It is a perennial herbaceous plant with purplish stem and milky-white exudates. This study was aimed at evaluation of the analgesic and antioxidant effects of the methanolic extract of O. turpethum leaves in mice. Methods: The acute oral toxicity of the extract was evaluated using up and down method. The analgesic effects were assessed using acetic acid-induced abdominal writhing reflex and tail flick methods, while the antioxidant activity (AA) was assayed using photometric 2, 2-diphenyl-1-picrylhydrazyl free radical scavenging assay method. Results: The extract produced a concentration-dependent increase in the AA with inhibitory concentration 50% >400 μg/ml. The extract (100, 200 and 400 mg/kg) and aspirin (100 mg/kg) produced a significant (p<0.05) dose-dependent reduction in the number of abdominal constriction induced by intraperitoneal injection of acetic acid in treated mice when compared to the distilled water treated mice. The extract (100, 200, and 400 mg/kg) and pentazocine (3 mg/kg) caused a significant (p<0.05) dose-dependent increase in the pain reaction time in the treated mice groups, when compared to the distilled water treated groups. Conclusion: The study showed that O. turpethum possesses analgesic and antioxidant properties and confirmed the folkloric use of O. turpethum leaves in the traditional pain management.

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.

Evaluación de la actividad analgésica central de las hojas de Maytenus macrocarpa (Ruiz & Pav.) Briq. (chuchuhuasi) / Evaluation of the central analgesic activity of the leaves of Maytenus macrocarpa (Ruiz & Pav.) Briq. (chuchuhuasi)

Introducción: Maytenus macrocarpa Ruiz & Pav.) Briq (chuchuhuasi), es una planta medicinal peruana, a la cual se le atribuyen efectos: antidisentérico, antidiarreico, analgésico, antiinflamatorio, entre otros. Objetivo: explorar la actividad analgésica central de las hojas de M. macrocarpa, en ratones, mediante el modelo de retirada de la cola. Métodos: a 50 ratones albinos (25 g promedio), divididos en 5 grupos, se les administró por la vía oral lo siguiente: M. macrocarpa 1000 y 1500 mg/kg, Tramadol 10 mg/kg, agua destilada (placebo) 0,1ml /10 g, y un grupo control. Se evalúo el dolor en el roedor, midiendo el promedio del período de latencia, después de 6 mediciones de intervalos de 30 minutos. Asimismo, se determinó el porcentaje del efecto máximo posible (% MPE, por sus siglas en inglés). Resultados: chuchuhuasi 1000 mg/kg, presentó un basal de 2,781 segundos, frente a 4,135 segundos a los 120 minutos. Chuchuhuasi 1500 mg/kg, presentó un basal de 2,467 segundos, frente a 4,385 segundos a los 180 minutos; frente al control presentaron un valor p>0,05. Tramadol tuvo un basal de 2,030 segundos, frente a 5,173 segundos, a los 30 minutos; frente al control presento un valor p<0,05. El grupo placebo fue no significativo. El % MPE fue de 19 % para chuchuhuasi 1000 mg/kg, 14 % para chuchuhuasi 1500 mg/kg, y 37 % para Tramadol. Conclusión: el efecto analgésico central de las hojas de M. macrocarpa en el modelo de retirada de la cola fue no significativo, el máximo % MPE fue de 19 %, con chuchuhuasi a 1000 mg/kg.

Introduction: Maytenus macrocarpa (Ruiz & Pav.) Briq (chuchuhuasi) is a Peruvian medicinal plant which has been attributed antidysenteric, antidiarrheal, analgesic and anti-inflammatory effects, among others. Objective: explore the central analgesic activity of M. macrocarpa leaves in mice using the tail-flick model. Methods: fifty albino mice (25 g average weight) were divided into 5 groups and administered the following substances by oral route: M. macrocarpa 1 000 and 1 500 mg/kg, Tramadol 10 mg/kg, distilled water (placebo) 0.1 ml/10 g, and a control group. Pain was evaluated by estimating the average latency period after taking 6 measurements at 30 minute intervals. Percent maximum possible effect (% MPE) was also determined. Results: baseline time for chuchuhuasi 1 000 mg/kg was 2.781 seconds vs. 4.135 seconds at 120 minutes. Baseline time for chuchuhuasi 1 500 mg/kg was 2.467 seconds vs. 4.385 seconds at 180 minutes; p value vs. control was p>0.05. Baseline time for Tramadol was 2.030 seconds vs. 5.173 seconds at 30 minutes; p value vs. control was p>0.05. The placebo group was not significant. % MPE was 19 % for chuchuhuasi 1 000 mg/kg, 14 % for chuchuhuasi 1 500 mg/kg and 37 % for Tramadol. Conclusion: the central analgesic effect of M. macrocarpa leaves on the tail-flick model was not significant. Percent maximum possible effect was 19 % with chuchuhuasi 1 000 mg/kg.

One-time Exposure to General Anesthetics Alters Nociceptive Response and Nucleotide Hydrolysis in Infant Rats.

Aims: The objective was to evaluate the single exposure of general anesthetics with or without a surgical procedure at postnatal day 14 (P14) on nociceptive behavioral responses. Furthermore, we evaluated ectonucleotidase activities at P14 and P30. Place of Study: All experiments were performed at the Animal Experimentation Unit of Hospital de Clínicas de Porto Alegre. The Institutional Committee approved the experimental protocol f (GPPG-HCPA protocol No: 08149). Methodology: Fourteen-day-old male Wistar rats were divided into two experimental designs (ED): the 1st ED – control (C), isoflurane (ISO), isoflurane/surgery (ISO-SUR) and the 2nd ED – control (C), fentanyl/S(+)-ketamine (FK) and fentanyl/S(+)- ketamine/surgery (FK-SUR). Nociceptive responses were evaluated using the formalin and tail-flick tests, and the ectonucleotidase activities were evaluated by spinal cord synaptosome. All assessments were performed at P14 and P30. Results: The FK and FK-SUR groups displayed an increased latency at P30. For the ectonucleotidase activity analysis, the following results were observed: (a) in the 1st ED, the ISO group displayed a reduction in ATPase and ADPase, and both ISO and ISOSUR displayed a reduction in AMPase activity at P14; (b) in the 2nd ED, the FK group displayed an increase in AMPase activity at P14 and increased ATPase activity at P30, and both FK and FK-SUR exhibited an increase in AMPase activity at P30. Conclusion: Our results indicate that single administration of general anesthetics at P14 is able to promote changes in the nociceptive response in the intermediate-term, and in the ectonucleotidase activities in the short- and medium-terms.

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.

Ethyl-p-methoxycinnamate isolated from kaempferia galanga inhibits inflammation by suppressing interleukin-1, tumor necrosis factor-α, and angiogenesis by blocking endothelial functions

OBJECTIVE: The present study aimed to investigate the mechanisms underlying the anti-inflammatory and anti-angiogenic effects of ethyl-p-methoxycinnamate isolated from Kaempferia galanga. METHODS: The anti-inflammatory effects of ethyl-p-methoxycinnamate were assessed using the cotton pellet granuloma assay in rats, whereby the levels of interleukin-1 and tumor necrosis factor-α were measured in the animals' blood. In addition, the levels of interleukin, tumor necrosis factor, and nitric oxide were measured in vitro using the human macrophage cell line (U937). The analgesic effects of ethyl-p-methoxycinnamate were assessed by the tail flick assay in rats. The anti-angiogenic effects were evaluated first by the rat aortic ring assay and, subsequently, by assessing the inhibitory effects of ethyl-p-methoxycinnamate on vascular endothelial growth factor, proliferation, migration, and tube formation in human umbilical vein endothelial cells. RESULTS: Ethyl-p-methoxycinnamate strongly inhibited granuloma tissue formation in rats. It prolonged the tail flick time in rats by more than two-fold compared with the control animals. The inhibition of interleukin and tumor necrosis factor by ethyl-p-methoxycinnamate was significant in both in vivo and in vitro models; however, only a moderate inhibition of nitric oxide was observed in macrophages. Furthermore, ethyl-p-methoxycinnamate considerably inhibited microvessel sprouting from the rat aorta. These mechanistic studies showed that ethyl-p-methoxycinnamate strongly inhibited the differentiation and migration of endothelial cells, which was further confirmed by the reduced level of vascular endothelial growth factor. CONCLUSION: Ethyl-p-methoxycinnamate exhibits significant anti-inflammatory potential by inhibiting pro-inflammatory cytokines and angiogenesis, thus inhibiting the main functions of endothelial cells. Thus, ethyl-p-methoxycinnamate could be a promising therapeutic agent ...

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.