Hot Plate Model Research Articles

Antinociceptive and antioxidant activities of Hunteria umbellata stem bark: possible role of the serotonergic, opioidergic and dopaminergic pathways.

Background Hunteria umbellata (HU) (K. Schum) is used in ethnomedicine for the management of pain, diabetes mellitus and dysmenorrhoea. This study evaluated the analgesic and antioxidant activities of aqueous extract of HU stem bark and the possible mechanism(s) of action. Methods The antinociceptive effect of HU was evaluated using acetic acid mouse writhing, tail flick, hot plate and formalin-induced paw licking models. To establish the possible mechanism(s) of action of HU, separate group of animals were pretreated with naloxone (1 mg/kg, i.p.), atropine (1 mg/kg, i.p.), haloperidol (0.1 mg/kg, i.p.), ondansetron (1 mg/kg, i.p.) and phenoxybenzamine (0.1 mg/kg, i.p.), 15 min before HU. The in vivo and in vitro antioxidant potential was evaluated using established methods. Results The extract at 150 and 300 mg/kg, significantly (p<0.05) reduced the number of writhes and paw licking times and increased pain threshold in writhing assay, paw licking and hotplate tests respectively. Pretreatment of animals with ondansetron, naloxone and haloperidol, significantly (p<0.05 and p<0.01) attenuated the analgesic activity of HU. The extract demonstrated significant (p<0.05) radical scavenging activity (IC50 0.39 µg/mL), with high phenol content and reducing property. The total phenol content was 124.19 per gram of gallic acid. In vivo antioxidant assay showed significant (p<0.05) increase in catalase and superoxide levels. Conclusions Results obtained in this study suggest the involvement of serotonergic, opioidergic and dopaminergic pathways in the analgesic effect of HU stem bark, in addition to its potent antioxidant potential.

Anti-inflammatory, antinociceptive and antioxidant properties of Schinopsis brasiliensis bark

Ethnopharmacological relevanceSchinopsis brasiliensis is a native plant from Brazil, popularly used in folk medicine to relieve pain and treat inflammation. This study evaluated the antinociceptive and anti-inflammatory activities and antioxidant properties of the hydroethanol extract (HEE) and ethyl acetate fraction (EAF) obtained from S. brasiliensis bark. Materials and methodsThe HEE and EAF of S. brasiliensis bark (10, 30 and 100mg/kg, p.o.) were evaluated using models of analgaesia (formalin-induced licking and hot-plate models) or inflammation (licking response by formalin-induced and carrageenan-induced cell migration into the subcutaneous air pouch). The antioxidant activities of HEE and EAF (50, 100 and 200µg/ml) were evaluated using the lipoperoxidation method induced in egg yolk by 2′-azobis(2-amidinopropane) dihydrochloride (AAPH) and FeSO4. ResultsHEE and EAF presented a central antinociceptive effect (at 100mg/kg dose), increasing the baseline and area under the curve in the hot plate model. EAF (100mg/kg) significantly reduced (p< 0.005) the pain response in the first (45%) and second (35%) phases of the formalin-induced licking model, while HEE (100mg/kg) reduced (38%) only the pain response in the second phase. Regarding anti-inflammatory activity, EAF (100mg/kg) also inhibited the inflammatory process induced by subcutaneous carrageenan injection in the SAP model, reducing the amount of the cytokine TNF-α produced. ConclusionHEE and EAF from S. brasiliensis bark show pharmacological interest because they were able to inhibit the peripheral and central transmission of pain. Our data also suggest that the anti-inflammatory activity caused by EAF exposure occurs through the inhibition of the pro-inflammatory cytokine TNF-α, also reducing the spreading of the inflammatory processes by neutralizing reactive oxygen species, which are by-products in the biosynthesis of pain mediators.

Anti-inflammatory and analgesic activities of cupressuflavone from Cupressus macrocarpa: Impact on pro-inflammatory mediators.

Hit, Lead & Candidate Discovery Inflammation is a complex biological process that is generally occurs in response to pathological triggers. Both neurodegenerative diseases and cancer have been linked to inflammation. The analgesic and anti-inflammatory effects of cupressuflavone (CUF) isolated from Cupressus macrocarpa were examined. The analgesic effects of CUF (40, 80 and 160 mg/kg po) were assessed in the acetic acid-induced writhing and hot plate models in mice with diclofenac sodium as the reference standard (100 mg/kg). CUF dose-dependently inhibited the writhing response in mice by 25, 48, and 62%, at the three CUF doses with 160 mg/kg being equivalent to the diclofenac control. CUF dose-dependently increased the hot plate model reaction time with a maximal effect after 120 min. In the carrageenan-induced paw edema model of inflammation, CUF demonstrated anti-inflammatory activity by inhibiting paw edema by 55, 60, and 64% at doses of 40, 80, and 160 mg/kg po, respectively. CUF also reduced the plasma pro-inflammatory mediators PGE2 (44, 54, and 58%), TNF-α (26, 37, and 53%), IL-1β (19, 33, and 41%), and IL-6 (32, 44, and 55%) at the three doses tested with the highest dose having similar effects to diclofenac sodium (100 mg/kg). This finding from this study indicates that CUF has both analgesic and anti-inflammatory effects.

Alterations in nociception and morphine antinociception in mice fed a high-fat diet

Currently, more than 78.6 million adults in the United States are obese. A majority of the patient population receiving treatment for pain symptoms is derived from this subpopulation. Environmental factors, including the increased availability of food high in fat and sugar, contribute to the continued rise in the rates of obesity. The focus of this study was to investigate whether long-term exposure to a high-fat, energy-dense diet enhances baseline thermal and inflammatory nociception while reducing sensitivity to morphine-induced antinociception. Antinociceptive and hypothermic responses to morphine were determined in male and female C57BL/6N mice fed either a “western-style” diet high in fat and sucrose (HED) or a standard low-fat chow diet for 15 weeks. Antinociception was assessed using both the hot plate and tail flick tests of acute thermal pain and the formalin test of inflammatory pain. Acute administration of morphine dose-dependently increased antinociception in the hot plate and tail flick assays for mice of both sexes fed chow and HED. However, female mice displayed lower antinociceptive response to morphine compared to males in the tail-flick test. Hypothermic responses to acute morphine were also assessed in mice fed chow or HED. Male and female mice fed chow, and female mice fed HED displayed similar hypothermic responses to morphine. However, males fed HED did not exhibit morphine-induced hypothermia. Tolerance to the antinociceptive and hypothermic effects of morphine was assessed after ten days of repeated daily administration (10mg/kg morphine). Male mice fed chow or HED developed tolerance to morphine in the hot plate test. However, females fed HED did not. In the tail flick assay, only mice fed HED developed tolerance to morphine. All groups showed tolerance to morphine-induced hypothermia. In the formalin test, we found that both male and female mice fed HED had reduced sensitivity to the antinociceptive effects of morphine (6mg/kg). Collectively, these data suggest that sensitivity and tolerance to the antinociceptive effects of morphine may be dependent on diet and sex in the hot plate and tail flick thermal pain models, and that the acute antinociceptive effects of morphine in the formalin inflammatory pain model may also be dependent on these two factors. In addition, diet and sex can influence morphine-induced hypothermia. Exposure to an HED may lead to changes in neuronal signaling pathways that alter nociceptive responses to noxious stimuli in a sex-specific manner. Thus, dietary modifications might be a useful way to impact pain therapy.

Anti-Inflammatory and Analgesic Activities of Terminalia Muelleri Benth. (Combretaceae).

Preclinical Research The anti-inflammatory and analgesic activities of a polyphenol-rich fraction (TMEF) obtained from Terminalia muelleri Benth. were measured. The analgesic activity of TMEF was tested using acetic acid-induced writhing and hot plate models in mice. The anti-inflammatory activity was assessed using carrageenan-induced paw edema model by measuring PGE2 , TNF-α, IL-1β, and IL-6 plasma levels as well as the paw thickness. TMEF was tested at doses of 100, 200, and 400 mg/kg p.o. and diclofenac sodium was used as a standard (100 mg/kg) in all experiments. The group treated with 400 mg/kg of TMEF showed a greater inhibition in the number of writhes (by 63%) than the standard-treated group (61%). Pretreatment with TMEF increased the analgesic effect in hot plate test in a dose-dependent manner with a maximum effect after 120 min. TMEF pretreatment alos reduced the edema thickness by 48, 53, and 62% at the tested doses, respectively. TMEF administration inhibited the carrageenan-induced elevations in PGE2 (by 34, 43, and 47%), TNF-α (18, 28, and 41%), IL-1β (14, 22, and 29%), and IL-6 (26, 31, and 46%). Four phenolic compounds were isolated from Terminalia muelleri for the first time. Drug Dev Res 78 : 146-154, 2017. © 2017 Wiley Periodicals, Inc.

Anti-inflammatory, Antipyretic, and Antinociceptive Effects of a Cressa cretica Aqueous Extract.

Cressa cretica is a widely grown halophytic plant traditionally used for the treatment of different ailments. Previous investigations reported its biological activity on a wide spectrum of diseases. In this study, in vivo antinociceptive, anti-inflammatory, and antipyretic activities of C. cretica aqueous extract whole plant were evaluated. In addition, the total polyphenol content, the total flavonoid content, and the chemical characterization of the extract were performed. C. cretica showed writhing inhibition in acetic acid-induced peripheral nociception of 43 and 48 % at doses of 50 and 100 mg/kg, respectively. The same doses increased latency time in a hot plate model of central analgesia by 66 and 78 % compared to the control group, respectively. The acute anti-inflammatory effect of the extract was explored in the carrageenan-induced rat hind paw test. The inhibition of paw volume was better than that of the standard drug indomethacin. C. cretica significantly decreased rectal temperature in the rats injected with Brewer's yeast. C. cretica aqueous extract showed both central and peripheral antinociceptive activities and was effective as an anti-inflammatory and antipyretic. Phenolic compounds, including chlorogenic acids and flavonol glycosides, were identified by HPLC-PDA-ESI-MS techniques. These findings indicate the medicinal importance of this traditionally used plant as a therapeutic remedy for different ailments.

A comparative evaluation of analgesic and anti-inflammatory activities of two medicinal plants rubia cordifolia and cassia fistula in wistar albino rats

Background: Pain and inflammation are disabling accompaniments of many medical conditions. So, controlling both pain and inflammation assumes the top priority for the physician. Inflammation is a part of a complex biological response of vascular tissues to harmful stimuli such as pathogens, chemicals or irritants. Therapy of pain and inflammation has always been debatable.Methods: Rats were divided into 8 groups of 6 animals of each. The anti-inflammatory activity was studied with carrageenan induced rat paw edema and cotton pellet induced granuloma models. The analgesic activity was evaluated using Eddy’s hot plate model. The aqueous extract of Rubia cardifolia root and Cassia fistula leaf preparations were compared with Diclofenac in both acute and sub acute inflammatory models and also in pain model.Results: Various test result parameters were statistically analysed at P value &lt;0.5. In Eddy's hot plate model both RC and CF preparations prolonged the response reaction time, while CF preparation showed longer reaction time than that of RC preparation. In carrageenan induced paw edema and cotton pellet induced granuloma models, both RC and CF preparations showed significant decrease in paw edema volume and granuloma dry weight respectively, but less than that of Diclofenac. RC preparation found to have dose dependant in inflammatory models.Conclusions: RC root and CF leaf preparations were compared head to head and they have been found to have significant dose dependant analgesic activity and dose independent acute and sub acute anti inflammatory activities. Though CF leaf preparation appeared to be a good analgesic than RF root preparation, but failed to do so as an anti inflammatory agent in both inflammatory models. But both test preparations were not equivalent to Diclofenac in all three models.

Variable potentiation of analgesic anti- inflammatory activity of diclofenac by two medicinal plants rubia cordifolia and cassia fistula in wistar albino rats

Background: NSAIDS are commonly prescribed drugs in clinical practice. However, their usage is limited by their toxicity profile and research continues for an alternative therapy with higher efficacy and safety. Various plant preparations found to be safe and effective are emerging, but their interactions with synthetic drugs are not much known.Methods: Wistar rats were divided in to four groups of six animals each Rubia cordifolia (RC) root preparation and casissia fistula (CF) leaf preparation were studied with sub anti-inflammatory dose of diclofenac in various analgesic, acute and subacute inflammatory models and test results variables were expressed in mean reaction time, paw edema volume and granuloma weight respectively.Results: Various test results were tabulated, statistically analysed and significance was calculated at P value &lt;0.5. Eddy’s hot plate model did not show any significant change, but carrageenan induced paw edema model and cotton pellet induced granuloma model showed comparable decrease in paw edema volume and granuloma dry weight.Conclusions: Diclofenac, a standard analgesic and anti –inflammatory was not potentiated in pain model but it was potentiated in carrageenan and cotton pellet granuloma models in a variable manner. CF potentiates acute anti-inflammatory action, whereas RC potentiates subacute anti-inflammatory actions of diclofenac.

Antinociceptive Activity of Methanol Extract of Tabebuia hypoleuca (C. Wright ex Sauvalle) Urb. Stems

Objective: The aim of this study was to evaluate the antinociceptive activity of the methanol extract of Tabebuia hypoleuca stems (THME). Materials and Methods: The animals were divided into 5 groups of 8 mice for each test (negative controls, positive controls, and 3 groups treated with THME at doses of 150, 300, and 500 mg/kg, p.o.). The antinociceptive effect of THME was evaluated using the writhing, formalin, tail flick, and hot plate models in mice. Results: In the writhing test, THME (150, 300, and 500 mg/kg) produced significantly (p < 0.001) fewer writhes induced by acetic acid than in the control group. In the formalin test, the licking time for THME at doses of 300 and 500 mg/kg was significantly shorter (p < 0.001) compared to the control group in the first phase of the formalin test, whereas in the second phase only the dose of 500 mg/kg showed an antinociceptive effect. In addition, THME at doses of 300 and 500 mg/kg significantly increased the latency time in the tail flick test (p < 0.05 and p < 0.001, respectively) and in the hot plate test (p < 0.01 and p < 0.001, respectively) compared to the control group. Conclusions: These results show that THME had antinociceptive activity using several models of nociception, and they suggest that the effect is mediated by the participation of both peripheral and central antinociceptive mechanisms.

Quinoline Alkaloids Isolated from Choisya Aztec-Pearl and Their Contribution to the Overall Antinociceptive Activity of This Plant.

Choisya ‘Aztec-Pearl’, a hybrid of Choisya ternata and Choisya dumosa var. arizonica, had the antinociceptive activity in the ethanol extract (EECA) of its leaves evaluated. Two quinoline alkaloids, anhydroevoxine (A) and choisyine (C), isolated from these leaves were also tested. The results obtained pointed out to a very high antinociceptive activity measured by the hot plate model for EECA (at doses of 10, 30 and 100 mg/kg) as well as for A and C (at doses of 1, 3 and 10 mg/kg). The magnitude of the activity was two-fold higher than the one observed for the morphine treated animals for the higher doses of extracts/compounds (30, 100 mg/kg and 3, 10 mg/kg respectively). The mechanism of action for this activity was also investigated and it seems that for EECA as well as A and C, the opiate system plays an important role. Results have also shown that the nitric oxide (NO) system also play a pivotal role in the case of EECA and A while for C it seems that the cholinergic system have some involvement. The acute toxicity was evaluated for EECA with results showing no important toxic effect.

Anti-Inflammatory Properties and Chemical Characterization of the Essential Oils of Four Citrus Species.

Citrus fruits have potential health-promoting properties and their essential oils have long been used in several applications. Due to biological effects described to some citrus species in this study our objectives were to analyze and compare the phytochemical composition and evaluate the anti-inflammatory effect of essential oils (EO) obtained from four different Citrus species. Mice were treated with EO obtained from C. limon, C. latifolia, C. aurantifolia or C. limonia (10 to 100 mg/kg, p.o.) and their anti-inflammatory effects were evaluated in chemical induced inflammation (formalin-induced licking response) and carrageenan-induced inflammation in the subcutaneous air pouch model. A possible antinociceptive effect was evaluated in the hot plate model. Phytochemical analyses indicated the presence of geranial, limonene, γ-terpinene and others. EOs from C. limon, C. aurantifolia and C. limonia exhibited anti-inflammatory effects by reducing cell migration, cytokine production and protein extravasation induced by carrageenan. These effects were also obtained with similar amounts of pure limonene. It was also observed that C. aurantifolia induced myelotoxicity in mice. Anti-inflammatory effect of C. limon and C. limonia is probably due to their large quantities of limonene, while the myelotoxicity observed with C. aurantifolia is most likely due to the high concentration of citral. Our results indicate that these EOs from C. limon, C. aurantifolia and C. limonia have a significant anti-inflammatory effect; however, care should be taken with C. aurantifolia.

Anti-Inflammatory and Analgesic Activity of Methanolic and Hydro- Alcoholic Extract of Myrsine africana L. Fruits

Myrsine africana L. (Family Myrsinaceae) commonly known as mirting, is an evergreen shrub found wildly in tropical Asia to Africa. The plant has been traditionally used to treat various diseases and extensively used in folk medicine. The reported literature reveals that there is no pharmacological activities carried out on the fruits of M. africana in order to validate its traditional claim. The aim of the present study is to evaluate the anti-inflammatory and analgesic activity of methanolic and hydro-alcoholic extracts of fruits of M. africana at a dose level of 100, 200 and 500 mg/kg. The safety of drug was evaluated by sub-acute toxicity study as per OECD guidelines. The anti-inflammatory activity was carried out by carrageenan induced paw edema model and analgesic activity was done by hot plate, tail flick and acetic acid induced writhing methods. The maximum per cent inhibition of paw edema was found to be 57% in hydro-alcoholic extract at a dose level of 500 mg/kg in carrageenan induced paw edema model as compared to the standard drug ibuprofen (74.6%). The average response time at the dose of 500 mg/kg in tail flick and hot plate models was found to be 6.6 ± 0.79 mins and 6.89 ± 0.17 mins (at 120 mins and 90 mins) respectively which is comparable with the standard drug. In acetic acid writhing test both the extracts showed significant reduction in writhes as compared to standard. The pharmacological activities were found to be dose dependent. The acute toxicity study confirmed the drug to be non-toxic and safe. So it has been observed that the fruit of M. africana has marked beneficial effects against centrally and peripherally inflammation models and can be used to treat various disorders associated with inflammation.

Antinociceptive effect and mechanism of action of isatin, N-methyl isatin and oxopropyl isatin in mice

AimsThere has been growing interest in the synthesis of new derivatives from isatin, found in Isatis genus. Our objectives were to characterize the antinociceptive mechanism of action of isatin, N-methyl-isatin (MI) and N-methyl-3-(2-oxopropyl)-3-hydroxy-2-oxindole (MOI). Materials and methodsSubstances (0.1–10mg/kg, p.o.) were studied in chemical (paw licking induced by formalin, capsaicin or glutamate) or thermal (hot plate) models of nociception. The involvement of several systems was evaluated using different receptor antagonists. Key findingsAll three substances inhibit both phases of formalin-induced licking, increase the area under the curve and MI and MOI have a higher effect than that of morphine (in hot plate). Capsaicin and glutamate-induced licking were also reduced by all three substances. In the hot plate model, the antinociceptive effect of isatin was reduced by naloxone and atropine; naloxone, atropine and L-NAME reduced MI effect while naloxone, atropine, L-NAME, mecamylamine and ondansetron reduced MOI effect. SignificanceOur results suggest that isatin, MI and MOI: 1) present activity in models of nociception; 2) capsaicin and glutamate receptors seems to participate in the mechanism of action; 3) opioid, cholinergic, serotoninergic, nitrergic and adrenergic systems may be involved, at least in part, in the mechanism of action of some of these substances.

Antinociceptive activity of the essential oil from Artemisia ludoviciana

Ethnopharmacological relevanceAerial parts of Artemisia ludoviciana are widely used in Mexico for treating gastrointestinal disorders, painful complaints and diabetes. Aim of the studyTo establish the preclinical efficacy as antinociceptive agent of the essential oil (EO) from the aerial parts of A. ludoviciana using well-known animal models. Materials and methodsAcute antinociceptive effect of EO (1, 10, 31.6, 100, and 316mg/kg, i.p.) was evaluated using the hot plate and paw formalin models in mice. The motor effects were assessed with the rota-rod and open field assays. The volatile components obtained by headspace solid phase microextraction (HS-SPME) and hydrodistillation were determined using gas chromatography coupled with mass spectrometry (GC–MS) analysis. ResultsEO decreased first and second phases of formalin test; in the first stage, the better effect was obtained with the treatment of 316mg/kg but in the second phase, time licking was attenuated at the doses of 31.6, 100 and 316mg/kg. The effectiveness of EO (ED50=25.9mg/kg) for attenuating neurogenic pain was corroborated using the hot plate test. The antinociceptive action of EO was blocked by naloxone suggesting that its mode of action involved an opioid mechanism. Furthermore, EO (316mg/kg) did not affect animal motor and coordination functions when tested by the rota-rod and open field tests. The latter results indicated that the pharmacological effects exerted by EO during the hot plate and formalin test are truly antinociceptive. GC–MS analysis of EO revealed that (±)-camphor, γ-terpineol, 1,8-cineole and borneol were the major volatile compounds of the plant. ConclusionEO from A. ludoviciana showed significant antinociceptive effect, which appeared to be partially mediated by the opioid system. These findings could support the long-term use of A. ludoviciana for treating painful complaints in Mexican folk medicine.

Pharmacological evidence favouring the traditional use of the root bark of Condalia buxifolia Reissek in the relief of pain and inflammation in mice

Ethnopharmacological relevanceThe Condalia buxifolia root bark infusion is used in traditional medicine in Brazil as antipyretic, anti-inflammatory and against dysentery. This study was designed to investigate whether the methanolic extract of the root bark of Condalia buxifolia (MECb) exhibits antinociceptive and anti-inflammatory effects in mice. Furthermore, also was investigated the involvement of glutamatergic and opioidergic system in the antinociceptive effect induced by MECb. Materials and methodsThe antinociceptive and anti-inflammatory effects of intra-gastric gavage (i.g.) administered MECb (10–300mg/kg) were evaluated in mice subjected to chemical (formalin, acetic-acid, glutamate) or thermal (hot plate) models of pain. The involvement of opioid system in the antinociceptive effect of the MECb was investigated in formalin test. Furthermore, a nonspecific effect of MECb was evaluated by measuring locomotor activity and exploratory behavior in open field test. Finally, was performed a phytochemical analysis of MECb. ResultsThe phytochemical analysis of MECb was performed through HPLC analysis showing that the alkaloid Condaline-A is the main constituent. The intragastric administration of MECb (100–300mg/kg) significantly inhibited the nociception caused by acetic acid (48±2%), inflammatory phase (49±3%) and paw edema (32±6) caused by formalin, and MECb (100mg/kg, i.g.) also inhibited nociception caused by glutamate (41±7%). In addition, MECb (100–300mg/kg, i.g.) increased the paw withdrawal latency in hot-plate test, without affecting the locomotor activity and exploratory behavior in open field test. Finally, the antinociceptive effects of MECb (100mg/kg, i.g.) were significantly reversed by naloxone (1mg/kg, i.p.) in the formalin test. ConclusionThese data show, for the first time, that MECb has significant antinociceptive and anti-inflammatory effects, which appear to be related to the inhibition of the glutamatergic system and the activation of opioid mechanism, besides present central effects. These results support the use of Condalia buxifolia in traditional medicine and demonstrate that this plant has therapeutic potential for the development of phytomedicines with antinociceptive and anti-inflammatory properties.

English

The analgesic and anti-inflammatory effects of the ethanol extract of Elytraria marginata were studied using hot plate, thermal-induced pain and carrageenan-induced acute inflammation models in adult Wister rats. The preliminary phytochemical constituents of the extract were also ascertained. Inflammation was induced by injecting 0.1 ml of 1% carrageenan into the sub-planter surface of the right hind paw of the rats. Ethanol extract of E. marginata with doses of 50, 100 and 150 mg/kg and diclofenac 10 mg/kg were administered orally to separate groups of rats. Control group received 10 ml/kg of distilled water. The results showed that the extract (50, 100 and 150 mg/kg) significantly (p<0.05) reduced the carrageenan-induced rat paw oedema in a dose-dependent manner. The oedema reductions at a dose of 150 mg/kg at the 4th h were comparable to that obtained for diclofenac, the standard anti-inflammatory drug at the 3rd hour. The extract also showed a very good analgesic response against hot plate-induced analgesia (thermal stimuli) in the rats. Administration of the extract doses (50, 100 and 150 mg/kg) and ibuprofen 100 mg/kg produced a significant (p<0.05) reduction in the pain induced by the hot plate (thermal stimuli) in all the experimental groups when compared with the control. Preliminary phytochemical analysis showed the presence of alkaloids, flavonoids, tannins and saponins. These findings indicate that the ethanol extract of E. marginata has both analgesic and anti-inflammatory effects and could be beneficial in alleviating painful inflammatory conditions. Key words: Elytraria marginata plant, inflammation, analgesia, diclofenac sodium, ibuprofen.

Analgesic activity of Gleditsia triacanthos methanolic fruit extract and its saponin-containing fraction

Context: Gleditsia triacanthos L. (Leguminosae) pods are used in folk medicine for pain relief as anodyne and narcotic.Objective: The objective of this study is to evaluate analgesic activity of Gleditsia triacanthos methanolic fruit extract (MEGT) and its saponin-containing fraction (SFGT).Materials and methods: Peripheral analgesic activity was assessed using the acetic acid-induced writhing model in mice at doses of 140, 280, and 560 mg/kg and formalin test in rats at 100, 200, and 400 mg/kg doses. Central analgesic activity was evaluated using the hotplate method in rats (100, 200, and 400 mg/kg).Results: In the writhing test, six mice groups treated with MEGT and SFGT found ED50 values 268.2 and 161.2 mg/kg, respectively, displayed a significant decrease in writhing count compared with the group treated with standard drug indomethacin (14 mg/kg). SFGT (280 and 560 mg/kg) showed 64.94 and 70.78% protection, respectively, which are more than double % protection caused by indomethacin (31.82%). In the formalin test, MEGT and SFGT (ED50 values 287.6 and 283.4 mg/kg for phase I as well as 295.1 and 290.4 mg/kg for phase II, respectively) at 400 mg/kg showed significant % inhibition in both phase I (18.86 and 52.57%) and phase II (39.36 and 44.29%) with reference to 10 mg/kg indomethacin (56.0 and 32.29%). MEGT and SFGT caused significant delay in responses in hotplate model (ED50 values 155.4 and 200.6 mg/kg, respectively) compared with that of 10 mg/kg indomethacin at 30, 60, and 120 min.Discussion and conclusion: Central and peripheral analgesic activities induced by Gleditsia triacanthos fruits might account for its uses in folk medicine.

Antinociceptive activity of the essential oil from Artemisia ludoviciana

Abstract Ethnopharmacological relevance Aerial parts of Artemisia ludoviciana are widely used in Mexico for treating gastrointestinal disorders, painful complaints and diabetes. Aim of the study To establish the preclinical efficacy as antinociceptive agent of the essential oil (EO) from the aerial parts of A. ludoviciana using well-known animal models. Materials and methods Acute antinociceptive effect of EO (1, 10, 31.6, 100, and 316 mg/kg, i.p.) was evaluated using the hot plate and paw formalin models in mice. The motor effects were assessed with the rota-rod and open field assays. The volatile components obtained by headspace solid phase microextraction (HS-SPME) and hydrodistillation were determined using gas chromatography coupled with mass spectrometry (GC–MS) analysis. Results EO decreased first and second phases of formalin test; in the first stage, the better effect was obtained with the treatment of 316 mg/kg but in the second phase, time licking was attenuated at the doses of 31.6, 100 and 316 mg/kg. The effectiveness of EO (ED 50 =25.9 mg/kg) for attenuating neurogenic pain was corroborated using the hot plate test. The antinociceptive action of EO was blocked by naloxone suggesting that its mode of action involved an opioid mechanism. Furthermore, EO (316 mg/kg) did not affect animal motor and coordination functions when tested by the rota-rod and open field tests. The latter results indicated that the pharmacological effects exerted by EO during the hot plate and formalin test are truly antinociceptive. GC–MS analysis of EO revealed that (±)-camphor, γ-terpineol, 1,8-cineole and borneol were the major volatile compounds of the plant. Conclusion EO from A. ludoviciana showed significant antinociceptive effect, which appeared to be partially mediated by the opioid system. These findings could support the long-term use of A. ludoviciana for treating painful complaints in Mexican folk medicine.

Antinociceptive Activity and Toxicity Evaluation of the Fatty Oil from Plukenetia polyadenia Mull. Arg. (Euphorbiaceae).

Seed oil (Pp-oil) of Plukenetia polyadenia is used by native people of the Brazilian Amazon against arthritis and rheumatism, spreading it on the arms and legs to reduce the pain and inflammation. Pp-oil was obtained by pressing dried seeds at room temperature to give a 47.0% yield of oil. It was then subjected to fatty acid composition analysis. The principal fatty acids were linoleic acid (46.5%), α-linolenic acid (34.4%) and oleic acid (13.9%). Then, it was evaluated for its antinociceptive activity in mice, using the acetic acid-induced abdominal writhing, hot plate and formalin test models. Additionally, its toxicity was determined. The Pp-oil proved to have no toxicological effects, showing dose-dependent antinociceptive effect under chemical stimulation. At oral doses of 25–100 mg/kg, Pp-oil significantly reduced the abdominal writhes in the writhing test. A higher oral dose of 200 mg/kg did not induce alterations in the latency time of the hot plate test when compared to the control, suggesting an analgesic activity of peripheral origin. At oral doses of 50 and 100 mg/kg, the Pp-oil significantly reduced the second phase of the algic stimulus in the formalin test. In addition, the antinociception of Pp-oil was reversed by naloxone in the evaluation of its mechanism of action. Therefore, the Pp-oil proved to be safe at very high doses and to show significant analgesic properties. The role of Pp-oil is still being investigated with respect the mechanism of action, but the results suggest that opiod receptors could be involved in the antinociception action observed for the oil of P. polyadenia.

Evaluation of analgesic activity of allopurinol and febuxostat in experimental analgesic models in mice

Background: Allopurinol and febuxostat are xanthine oxidase inhibitors which are used in the treatment of hyperuricemia and gout. Pain is one of the important symptoms in gout patients. The present study was to evaluate the analgesic activity of allopurinol and febuxostat in two analgesic models in mice. Materials and Methods: The analgesic activity of allopurinol (39 mg/kg) and febuxostat (15.6 mg/kg) was evaluated using central analgesic model of Eddy's hot plate and peripheral analgesic model of acetic acid induced writhing. Both drugs were compared with the positive control, pentazocine for a hot plate method and aspirin for the writhing method. Furthermore, both allopurinol and febuxostat were compared with each other. Results: Both allopurinol and febuxostat showed significant increase in reaction time at various time periods in hot plate method and also showed significant delay in onset of writhing as well as decrease in number of writhes in writhing method. As compared to positive control result, allopurinol and febuxostat result were lower. Febuxostat shows better analgesic activity as compared to that of allopurinol. Conclusion: Allopurinol and febuxostat exhibited analgesic activity in both central and peripheral models of pain.