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1.  Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice 
BMC Pharmacology  2002;2:7.
Crocus sativus L. (saffron) is used in folk medicine, for example as an antiedematogenic agent. We aimed to evaluate the antinociceptive and anti-inflammatory activity of saffron extracts in mice.
We used aqueous and ethanolic maceration extracts of Crocus sativus L. stigma and petals. Antinociceptive activity was examined using the hot plate and writhing tests. The effect of extracts against acute inflammation was studied using xylene induced ear edema in mice. The activity of the extracts against chronic inflammation was assessed by formalin-induced edema in the rat paw. In the hot plate tests, intraperitoneal injection of both extracts showed no significant antinociceptive activity in mice. The extracts exhibited antinociceptive activity against acetic acid induced writhing. Naloxone partially blocked only the antinociceptive activity of the stigma aqueous extract. Only the stigma extracts showed weak to moderate effect against acute inflammation. In chronic inflammation, both aqueous and ethanolic stigma extracts, as well as ethanolic petal extract, exerted anti-inflammatory effects.
We conclude that aqueous and ethanolic extracts of saffron stigma and petal have an antinociceptive effect, as well as acute and/or chronic anti-inflammatory activity.
PMCID: PMC101384  PMID: 11914135
2.  Antinociceptive Activity of Melicope ptelefolia Ethanolic Extract in Experimental Animals 
Melicope ptelefolia is a medicinal herb commonly used in Malaysia to treat fever, pain, wounds, and itches. The present study was conducted to evaluate the antinociceptive activity of the Melicope ptelefolia ethanolic extract (MPEE) using animal models of nociception. The antinociceptive activity of the extract was assessed using acetic acid-induced abdominal writhing, hot-plate, and formalin-induced paw licking tests. Oral administration of MPEE produced significant dose-dependent antinociceptive effects when tested in mice and rats using acetic acid-induced abdominal constriction test and on the second phase of the formalin-induced paw licking test, respectively. It was also demonstrated that MPEE had no effect on the response latency time to the heat stimulus in the thermal model of the hot-plate test. In addition, the antinociception produced by MPEE was not blocked by naloxone. Furthermore, oral administration of MPEE did not produce any effect in motor performance of the rota-rod test and in acute toxicity study no abnormal behaviors as well as mortality were observed up to a dose level of the extract of 5 g/kg. These results indicated that MPEE at all doses investigated which did not produce any sedative and toxic effects exerted pronounce antinociceptive activity that acts peripherally in experimental animals.
PMCID: PMC3022215  PMID: 21274262
3.  Antinociceptive Activity of Ethanol Extract from Duguetia chrysocarpa Maas (Annonaceae) 
The Scientific World Journal  2012;2012:859210.
The ethanol extract from the fruits of Duguetia chrysocarpa was evaluated for its antinociceptive activity in chemical and thermal models of nociception in mice. The intraperitoneal administration of the ethanol extract (100, 200, and 400 mg/kg body weight) showed a dose-dependent inhibition of acetic-acid-induced abdominal writhes. The extract also produced a significant inhibition of both phases of the formalin test in all doses tested and increased the reaction time in hot-plate test at dose of 200 mg/kg. The data obtained suggest that the antinociceptive effect of the extract may be mediated via both peripheral and central mechanisms. The phytochemical investigation yielded the isolation of the benzenoid derivative 3-methoxy-4-ethoxy benzoic acid which is being reported for the first time in this genus.
PMCID: PMC3356742  PMID: 22645460
4.  Study of central nervous system depressant and behavioral activity of an ethanol extract of Achyranthes aspera (Agadha) in different animal models 
Achyranthes aspera Linn., an indigenous herb, has been reported to have antifertility, antihyperlipidemic, antidiabetic, immunomodulatory, anticarcinogenic, diuretic, cardiotonic, analgesic anti-inflammatory, hypnotic, antifungal, antibacterial, and central antinociceptive activities.
This study was designed to evaluate depressant effects on central nervous system (CNS) and behavioral effects of ethanol extract of A. aspera (EEAA) and to find the phytochemical responsible for these activities.
Materials and Methods:
The pharmacological assays used to study CNS depressant effect in albino mice were rota rod and actophotometer performance test. Effects on behavioral activity were studied using open field test. The extract was given intraperitoneally (i.p.) at a dose of 400 mg/kg. Diazepam (2 mg/kg body weight i.p.) was used as standard.
Statistical Analysis Used:
Data were analyzed by using analysis of variance followed by Dunnett's test. P < 0.05 was considered significant.
Phytochemical screening revealed presence of triterpenoids, saponins, alkaloids (betaine, achyranthine), and steroids as major constituents. The result of this study reflected that EEAA (400 mg/kg i.p.) decreased locomotor activity, produced muscle relaxation, and showed anxiolytic activity.
EEAA exhibit CNS depressant and significant anxiolytic activity comparable to diazepam.
PMCID: PMC3657964  PMID: 23776787
Achyranthes aspera; actophotometer; open field test; rota-rod
5.  Antinociceptive activity of Ricinus communis L. leaves 
To evaluate the antinociceptive activity of the methanol extract of Ricinus communis leaves (MRCL).
Antinociceptive activity was evaluated using acetic acid induced writhing test, formalin induced paw licking and tail immersion method in mice at doses of 100, 125 and 150 mg/kg bw.
The results indicated that MRCL exhibited considerable antinociceptive activity against three classical models of pain in mice. Preliminary phytochemical analysis suggested the presence of saponin, steroids and alkaloids.
It can be concluded that MRCL possesses antinociceptive potential that may be due to saponin, steroids and alkaloids in it.
PMCID: PMC3609173  PMID: 23569744
Ricinus communis; Analgesic; Antinociceptive; Writhing; Formalin
6.  Phytochemical Analysis and Antimicrobial, Antinociceptive, and Anti-Inflammatory Activities of Two Chemotypes of Pimenta pseudocaryophyllus (Myrtaceae) 
Preparations from Pimenta pseudocaryophyllus (Gomes) L.R. Landrum (Myrtaceae) have been widely used in Brazilian folk medicine. This study aims to evaluate the antimicrobial activity of the crude ethanol extracts, fractions, semipurified substances, and essential oils obtained from leaves of two chemotypes of P. pseudocaryophyllus and to perform the antinociceptive and anti-inflammatory screening. The ethanol extracts were purified by column chromatography and main compounds were spectrally characterised (1D and 2D 1H and 13C NMR). The essential oils constituents were identified by GC/MS. The broth microdilution method was used for testing the antimicrobial activity. The abdominal contortions induced by acetic acid and the ear oedema induced by croton oil were used for screening of antinociceptive and anti-inflammatory activities, respectively. The phytochemical analysis resulted in the isolation of pentacyclic triterpenes, flavonoids, and phenol acids. The oleanolic acid showed the best profile of antibacterial activity for Gram-positive bacteria (31.2–125 μg mL−1), followed by the essential oil of the citral chemotype (62.5–250 μg mL−1). Among the semipurified substances, Ppm5, which contained gallic acid, was the most active for Candida spp. (31.2 μg mL−1) and Cryptococcus spp. (3.9–15.6 μg mL−1). The crude ethanol extract and fractions from citral chemotype showed antinociceptive and anti-inflammatory effects.
PMCID: PMC3469278  PMID: 23082081
7.  Antinociceptive and Antioxidant Activity of Zanthoxylum budrunga Wall (Rutaceae) Seeds 
The Scientific World Journal  2014;2014:869537.
Different parts of the medicinal plant Zanthoxylum budrunga Wall enjoy a variety of uses in ethnobotanical practice in Bangladesh. In the present study, a number of phytochemical and pharmacological investigations were done on the ethanol extract of Z. budrunga seeds (ZBSE) to evaluate its antinociceptive and antioxidant potential. ZBSE was also subjected to HPLC analysis to detect the presence of some common antioxidants. In acetic acid induced writhing test in mice, ZBSE showed 65.28 and 74.30% inhibition of writhing at the doses of 250 and 500 mg/kg and the results were statistically significant (P < 0.001). In hot-plate test, ZBSE raised the pain threshold significantly (P < 0.001) throughout the entire observation period. In DPPH scavenging assay, the IC50 of ZBSE was observed at 82.60 μg/mL. The phenolic content was found to be 338.77 mg GAE/100 g of dried plant material. In reducing power assay, ZBSE showed a concentration dependent reducing ability. HPLC analysis indicated the presence of caffeic acid with a concentration of 75.45 mg/100 g ZBSE. Present investigation supported the use of Zanthoxylum budrunga seed in traditional medicine for pain management. Constituents including caffeic acid and other phenolics might have some role in the observed activity.
PMCID: PMC3951088
8.  Antinociceptive and Anti-inflammatory Effects of Pistacia vera LeafExtract in Mice 
Pistacia vera L., a member of Anacardiaceae family, has been used for sedation and analgesia in traditional medicine. In this study, the antinociceptive and anti-inflammatory effects as well as acute toxicity of the aqueous and ethanolic extracts of P. vera leaves were investigated in mice. The antinociceptive activity was studied using hot plate and writhing tests. The effect of the extracts against acute inflammation was determined using xylene-induced ear edema and the activity of the extracts, against chronic inflammation, was assessed using the cotton pellet test. The LD50 values of the infusion and maceration extracts were 0.8 g/Kg and 0.79 g/Kg, respectively. The aqueous and ethanolic maceration extracts of the P. vera leaves at the doses of 0.4 g/Kg and 0.5 g/Kg (IP), respectively, showed antinociceptive effects. The pretreatment of naloxone (2 mg/Kg, SC) inhibited the activities of extracts in hot plate test, but naloxone at the same dose could not inhibit the antinociceptive activity in writhing test. The extracts also showed anti-inflammatory effects in acute and chronic anti-inflammatory tests. The ethanolic extract was as effective as diclofenac in both inflammatory tests. The aqueous and ethanolic extracts of P. vera leaves demonstrated central and peripheral antinociceptive activities dose-dependently and the central effect may be mediated by opioid system. The extracts also demonstrated anti-inflammatory effects against acute and chronic inflammation.
PMCID: PMC3813078  PMID: 24250418
Pistacia vera; Antinociceptive; Anti-inflammatory; Hot plate test; Writhing test; Xylene-induced ear edema; Cotton pellet test.
9.  Antinociceptive, anti-inflammatory, antimicrobial and central nervous system depressant activities of ethanolic extract of leaves and roots of Gomphostemma parviflorum var. parviflorum wall 
Pharmacognosy Research  2013;5(4):233-240.
Gomphostemma parviflorum (Lamiaceae) is a medicinal plant of Bangladesh which has been used traditionally in the treatment of painful and inflammatory conditions such as asthma, headache, fever, etc.
To investigate the antinociceptive, anti-inflammatory, central nervous system (CNS) depressant and antimicrobial activities of ethanolic extracts of leaves (GPLE) and roots (GPRE) of the plant.
Materials and Methods:
The antinociceptive potentials of the extracts were studied using acetic acid-induced writhing test in mice, anti-inflammatory activity was investigated using carrageenan-induced paw edema in rats, CNS depressant activities were evaluated using pentobarbitone-induced sleeping time, Hole cross and Open field tests in mice while the anti-microbial activity was studied by in vitro disc diffusion method.
The extracts GPLE and GPRE significantly (P < 0.001) and dose dependently inhibited the acetic acid-induced writhing in mice with 73.15% and 53.69% inhibition, respectively at the dose of 200 mg/kg. At the same dose GPLE and GPRE significantly inhibited carrageenan-induced rats paw edema at the end of 4 hour with 35.54% and 28.17% inhibition, respectively. The extracts significantly prolonged the pentobarbitone-induced sleeping time and decreased the locomotory activities in open field and Hole cross tests in mice. The GPLE showed strong antimicrobial activity against Gram-positive and Gram-negative bacteria with zones of inhibition ranging from 8 to 20 mm at a concentration of 400 μg/disc.
The findings of the study indicate that the leaves and roots of G. parviflorum possess antinociceptive, anti-inflammatory and CNS depressant activity and revealed the antimicrobial activities of leaves extract of the plant. The results justify the traditional use of the plant in the treatment of painful and inflammatory disorders.
PMCID: PMC3807986  PMID: 24174815
Anti-inflammatory; antimicrobial activities; antinociceptive; central nervous system depressant; Gomphostemma parviflorum; writhing
10.  Antinociceptive, Anti-Inflammatory and Acute Toxicity Effects of Juglans Regia L. Leaves in Mice 
Juglans regia leaves have been used in folk medicine to alleviate inflammatory diseases. This study investigates the antinociceptive, anti-Inflammatory and acute toxicity effects of Juglans regia L. leaves in mice.
351 Male and female albino mice were divided into negative (saline), positive (morphine or diclofenac) controls as well as test groups (n=6-8). The acute (intraperitoneally) toxicity was evaluated for 2 days. Antinociceptive activities were done using hot-plate and writhing tests. Anti-inflammatory effects were studied using xylene induced ear edema and cotton pellet tests.
The LD50 values of J. regia aqueous and ethanolic extrats were 5.5 and 3.3 g/kg, respectively. The aqueous (2.87 and 1.64 g/kg) and ethanolic (2.044 and 1.17 g/kg) extracts showed antinociceptive activity in hot-plate test. The pretreatment of naloxone (2 mg/kg, s.c.) did not inhibit the extracts activities. The extracts exhibited antinociceptive activity in writhing test, which were not blocked by naloxone. In xylene test, both extracts showed anti-inflammatory activity in some doses. The extracts showed anti-inflammatory activity against the chronic inflammation.
J. regia leaves demonstrated antinociceptive effect through non-opioid receptors and anti-inflammatory effect against acute and chronic inflammation. The extracts of J. regia could be considered as a promising analgesic and anti-inflammatory agents against diseases such as rheumatoid arthritis.
PMCID: PMC3407583  PMID: 22946016
Juglans regia; Hot-plate test; Writhing test; Xylene induced ear edema test; Cotton pellet test; Mice
11.  Antinociceptive and Anti-Inflammatory Activity from Algae of the Genus Caulerpa 
Marine Drugs  2011;9(3):307-318.
Marine natural products have been the focus of discovery for new products of chemical and pharmacological interest. The aim of this study was to evaluate the antinociceptive activity of the methanolic (ME), acetate (AE), hexanic (HE) and chloroform (CE) extracts obtained from Caulerpa mexicana, and ME, CE and HE obtained from Caulerpa sertularioides. These marine algae are found all over the world, mainly in tropical regions. Models such as the writhing test, the hot plate test and formalin-induced nociception test were used to evaluate antinociceptive activity in laboratory mice. In the writhing test, all the extracts were administered orally at a concentration of 100 mg/kg, and induced high peripheral antinociceptive activity, with a reduction in the nociception induced by acetic acid above 65%. In the hot plate test, treatment with extracts from C. sertularioides (100 mg/kg, p.o.) did not significantly increase the latency of response, although the ME, AE and HE from C. mexicana showed activity in this model. This result suggests that these extracts exhibit antinociceptive activity. In the formalin test, it was observed that ME, AE and HE obtained from C. mexicana reduced the effects of formalin in both phases. On the other hand only CE from C. sertularioides induced significant inhibition of the nociceptive response in the first phase. To better assess the potential anti-inflammatory activity of the extracts, the carrageenan-induced peritonitis test was used to test Caulerpa spp. extracts on cell migration into the peritoneal cavity. In this assay, all extracts evaluated were able to significantly inhibit leukocyte migration into the peritoneal cavity in comparison with carrageenan. These data demonstrate that extracts from Caulerpa species elicit pronounced antinociceptive and anti-inflamatory activity against several nociception models. However, pharmacological and chemical studies are continuing in order to characterize the mechanism(s) responsible for the antinociceptive action and also to identify the active principles present in the Caulerpa species.
PMCID: PMC3083652  PMID: 21556161
antinociceptive; anti-inflammatory; Caulerpa mexicana; Caulerpa sertularioide; marine algae
12.  Analysis of chemical constituents and antinociceptive potential of essential oil of Teucrium Stocksianum bioss collected from the North West of Pakistan 
Medicinal plants are used for the treatment of different diseases in almost all cultures. Teucrium species grow wildly at different geographical locations around the world. Teucrium stocksianum is used in folk medicine for the treatment of diarrhea, cough, jaundice and abdominal pain. Scientific study on Teucrium stocksianum shows that it possesses anthelmintic, cytotoxic and antispasmodic activity. The aim of our present study is to identify the chemical composition and antinociceptive potential of the essential oil extracted from Teucrium stocksianum bioss.
Essential oil (EO) from the aerial parts of Teucrium stocksianum were extracted by hydrodistillation process. The qualitative and quantitative composition of essential oil was determined with Gas chromatography/Mass spectrometer. Antinociceptive activity was determined by acetic acid induced writhing method. Percent inhibition of writhes of the test concentration was determined by comparing it with that of control. Tween-80 emulsion 2.5% (5 ml/kg b.w) was used as a control while Diclofenic sodium 50 mg/kg (b.w) was used as a standard drug.
The chromatogram of the essential oil of Teucrium stocksianum shows differences both qualitatively and quantatively from essential oil composition reported in other countries. Hydrodistillation of Teucrium stocksianum yielded 0.4% (v/w), pale yellowish oil on dry basis. A total of 26 chemicals were identified by GC-MS accounting for 90.28% of the oil. The major components of essential oil were δ-cadinene (12.92%), α-pinene (10.3%), myrcene (8.64%), β-caryophyllene (8.23%), germacrene D (5.18%) and limonene (2.36%). Essential oil of Teucrium stocksianum has shown outstanding antinociceptive activity. It has been observed that increase in percent writhe inhibition (PWI) occurred from 20-80 mg/kg (b.w) and maximum writhe inhibition has been noted at a concentration of 80 mg/kg (b.w), but PWI decreased at 160 mg/kg, which may be due to some toxic effect of higher dose. ED50 value for Teucrium stocksianum was calculated as 31.5 ± 1.72415 mg/kg (b.w).
Our results indicate that there is a lot of variation in the composition of essential oil of Teucrium stocksianum boiss, which may be due to different climatic and experimental conditions. Secondly, the essential oil possesses strong antinociceptive activity and could be used in analgesic preparations especially for topical use.
PMCID: PMC3534250  PMID: 23217213
Teucrium stocksianum; Antinociceptive; Essential oil
13.  Hop Extract Produces Antinociception by Acting on Opioid System in Mice 
In the present study, the antinociceptive profiles of hop extract were characterized in ICR mice. Hop extract administered orally (from 25 to 100 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. Antinociceptive action of hop extract was maintained at least for 60 min. Moreover, cumulative response time of nociceptive behaviors induced with intraplantar formalin injection was reduced by hop extract treatment during the 2nd phases. Furthermore, the cumulative nociceptive response time for intrathecal injection of substance P (0.7 µg) or glutamate (20 µg) was diminished by hop extract. Intraperitoneal pretreatment with naloxone (an opioid receptor antagonist) attenuated antinociceptive effect induced by hop extract in the writhing test. However, methysergide (a 5-HT serotonergic receptor antagonist) or yohimbine (an α2-adrenergic receptor antagonist) did not affect antinociception induced by hop extract in the writhing test. Our results suggest that hop extract shows an antinociceptive property in various pain models. Furthermore, the antinociceptive effect of hop extract may be mediated by opioidergic receptors, but not serotonergic and α2-adrenergic receptors.
PMCID: PMC3394921  PMID: 22802700
Hop; Antinociception; Inflammatory pain; Opioid receptor
14.  Antinociception Effect and Mechanisms of Campanula Punctata Extract in the Mouse 
In the present study, the antinociceptive profiles of Campanula punctata extract were examined in ICR mice. The Campanula punctata contain a large dose of saponin. Campanula punctata extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Campanula punctata extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 µg) was diminished by Campanula punctata extract. Intraperitoneal (i.p.) pretreatment with yohimbine (α2-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Campanula punctata extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Campanula punctata extract in the writhing test. Our results suggest that Campanula punctata extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Campanula punctata extract may be mediated by α2-adrenergic receptor, but not opioidergic and serotonergic receptors.
PMCID: PMC2997413  PMID: 21165326
Campanula punctata; Anti-nociception; Inflammatory pain; α2 adrenoceptor
15.  Effect of Agrimonia pilosa Ledeb Extract on the Antinociception and Mechanisms in Mouse 
In the present study, the antinociceptive profiles of Agrimonia pilosa Ledeb extract were examined in ICR mice. Agrimonia pilosa Ledeb extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Agrimonia pilosa Ledeb extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 µg) was diminished by Agrimonia pilosa Ledeb extract. Intraperitoneal (i.p.) pretreatment with yohimbine (α2-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Agrimonia pilosa Ledeb extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Agrimonia pilosa Ledeb extract in the writhing test. Our results suggest that Agrimonia pilosa Ledeb extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Agrimonia pilosa Ledeb extract may be mediated by α2-adrenergic receptor, but not opioidergic and serotonergic receptors.
PMCID: PMC3339287  PMID: 22563257
Agrimonia pilosa Ledeb; Anti-nociception; Inflammatory pain; α2 adrenoceptor
16.  Evaluation of antinociceptive activity of hydromethanol extract of Cyperus rotundus in mice 
Cyperus rotundus Linn. (Cyperaceae) is used to treat inflammation, pain, fever, wounds, boils and blisters in folk medicine. This study evaluated the antinociceptive effect of the hydromethanol extract of whole plant of C. rotundus (HMCR).
The antinociceptive activity of HMCR was investigated in thermal-induced (hot plate and tail immersion) and chemical-induced (formalin) nociception models in mice at three different doses (50, 100 and 200 mg/kg; p.o.). Morphine sulphate (5 mg/kg, i.p.) and diclofenac sodium (10 mg/kg, i.p.) were used as reference analgesic agents.
In the hot-plate and tail-immersion tests HMCR significantly increased the latency period to the thermal stimuli at all the tested doses (50, 100 and 200 mg/kg) (p < 0.05). The significant increase in latency is clear from the observations at 60 and 90 min. In formalin-induced paw licking test oral administration of HMCR at 100 and 200 mg/kg doses decreased the licking of paw in early phase. All the tested doses (50, 100 and 200 mg/kg) significantly decreased the licking of paw in late phase of the test (p < 0.001). The dose 200 mg/kg was most effective showing maximum percentage of inhibition of licking in both early (61.60%) and late phase (87.41%).
These results indicate the antinociceptive effect of C. rotundus and suggest that this effect is mediated by both peripheral and central mechanisms. These results support the traditional use of this plant in different painful conditions.
PMCID: PMC3946594  PMID: 24589067
Analgesic; Cyperaceae; Cyperus rotundus; Medicinal plant; Pain
17.  Antioxidant, Antinociceptive and Anti-inflammatory Activities of Ethanolic Extract of Leaves of Alocasia indica (Schott.) 
Extracts obtained from the leaves of various Alocasia species have been used in India as folk remedy for the treatment of various inflammatory ailments including rheumatism and bruise. The ethanolic extract of leaves of Alocasia indica Schott. was evaluated by using different in vitro antioxidant models of screening like scavenging of 1, 1-diphenyl-2-picryl hydrazyl (DPPH) radical, nitric oxide radical, superoxide anion radical, and hydroxyl radical. The antinociceptive activity was tested by acetic acid-induced writhing response, hot plate method, and tail flick method in albino rats. The anti-inflammatory potential of gels of ethanolic extract has been determined by using carrageenan-induced paw edema assay, formalin-induced paw edema assay, arachidonic acid-induced ear edema assay, and xylene-induced ear edema assay. The extract showed remarkable antioxidant activity in all models, comparable to the standard reference drug ascorbic acid. The ethanolic extract of Alocasia indica and its gels produced dose-dependent antinociceptive and anti-inflammatory activity, respectively. This finding suggests that ethanolic extract of A. indica possess potent antinociceptive and anti-inflammatory activity possibly due to its free radical scavenging properties.
PMCID: PMC3021687  PMID: 21264115
Alocasia indica Schott; antioxidant; antinociceptive; anti-inflammatory; ascorbic acid; diclofenac
18.  Antinociceptive effect of an ethanolic extract of the aerial parts of Hilleria latifolia (Lam.) H. Walt. (Phytolaccaceae) 
Hilleria latifolia (Lam.) H. Walt. (Phytolaccaceae) is a perennial herb used in Ghanaian traditional medicine for the treatment of various painful conditions. Little scientific evidence exists in literature on the effect of this plant on pain.
Materials and Methods:
The present study examined the antinociceptive effect of the ethanolic extract of the aerial parts of H. latifolia in chemical (acetic acid-induced abdominal writhing, glutamate, formalin, and capsaicin tests) and thermal (tail immersion test) behavioral pain models in rodents. The possible mechanisms of the antinociceptive action were also assessed with various antagonists in the formalin test.
The H. latifolia extract (HLE) together with morphine and diclofenac (positive controls), showed significant antinociceptive activity in all the models used. The antinociceptive effect exhibited by HLE in the formalin test was partly or wholly reversed by the systemic administration of naloxone, theophylline, and atropine. Glibenclamide, ondansetron, yohimbine, nifedipine, and NG-L-nitro-arginine methyl ester (L-NAME), however, did not significantly block the antinociceptive effect of the extract. HLE, unlike morphine, did not induce tolerance to its antinociceptive effect in the formalin test after chronic administration; morphine tolerance did not also cross-generalize to HLE. Interestingly, also, the chronic concomitant administration of HLE and morphine significantly suppressed the development of morphine tolerance.
Together, these results indicate that HLE produces dose-related antinociception in several models of chemical and thermal pain, without tolerance induction, through mechanisms that involve an interaction with adenosinergic, muscarinic cholinergic, and opioid pathways.
PMCID: PMC3178945  PMID: 21966159
Formalin; Hilleria latifolia; opioid tolerance; tail immersion; writhing
19.  The Antinociceptive and Anti-Inflammatory Activities of Aspidosperma tomentosum (Apocynaceae) 
The Scientific World Journal  2013;2013:218627.
We investigated the antinociceptive and anti-inflammatory activities of the crude ethanolic extract (CEE), its fractions, and the flavonoid isorhamnetin from Aspidosperma tomentosum using models of nociception and inflammation in mice. In the writhing test, the CEE and its fractions (except for soluble phase, CHCl3 100% and EtAcO 100%) at 100 mg/kg p.o. induced antinociceptive activity. Isorhamnetin (100 μmol/kg, p.o.) was also active. In the hot plate test, only the treatment with the fractions Hex : CHCl3 50%, CHCl3 100%, and CHCl3 : MeOH 5% (100 mg/kg, p.o.) increased the latency time, reversed by the opioid antagonist naloxone. Fractions that were active in the hot plate test did not show catalepsy condition. It was observed that CEE, all fractions, and isorhamnetin reduced the formalin effects in the neurogenic phase. In the inflammatory phase, only CEE, isorhamnetin, and CHCl3 100% and CHCl3 : MeOH 5% fractions were active. CEE and all fractions, except for CHCl3 : MeOH 10% fraction, isorhamnetin, and soluble fraction were able to produce an antioedematogenic activity in the ear capsaicin-induced edema test. In the thioglycolate-induced peritonitis, only EtAcO 100% fraction was not active. The results demonstrate that A. tomentosum has antinociceptive and anti-inflammatory activities in animal models.
PMCID: PMC3679822  PMID: 23781151
20.  Antinociceptive and Anti-Inflammatory Activities of the Ethanolic Extract from Synadenium umbellatum Pax. (Euphorbiaceae) Leaves and Its Fractions 
Synadenium umbellatum Pax., popularly known in Brazil as “cola-nota,” “avelós,” “cancerola,” and “milagrosa”, is a plant species used in folk medicine for the treatment of inflammation, pain, and several diseases. This study aimed to investigate the antinociceptive and anti-inflammatory activities of the ethanolic extract from Synadenium umbellatum Pax. leaves (EES) and its hexane (HF), chloroform (CF), and methanol/water (MF) fractions using the acetic acid-induced abdominal writhing test, formalin-induced paw licking test, tail flick test, croton oil-induced ear edema test, and carrageenan-induced peritonitis test. EES and MF reduced the number of acetic acid-induced abdominal writhes, while CF and HF did not. EES effect on acetic acid-induced abdominal writhing was reversed with a pretreatment with naloxone. EES reduced licking time in both phases of the formalin-induced paw licking test, but did not prolong the latency in the tail flick test. These results show that EES presented antinociceptive activity, probably involving the opioid system, anti-inflammatory activity in the croton oil-induced ear edema test, and leukocyte migration into the intraperitoneal cavity. MF also presented anti-inflammatory activity in the croton oil-induced ear edema test. In conclusion, EES and MF have antinociceptive activity involving the opioid system and anti-inflammatory activity.
PMCID: PMC3563172  PMID: 23401717
21.  Antinociceptive effect of geranylgeraniol and 6α,7β-dihydroxyvouacapan-17β-oate methyl ester isolated from Pterodon pubescens Benth 
BMC Pharmacology  2010;10:1.
Pterodon pubescens Benth seeds are commercially available in the Brazilian medicinal plant street market. The crude alcoholic extracts of this plant are used in folk medicine as anti-inflammatory, analgesic, and anti-rheumatic preparations. The aim of this study was to evaluate the contribution of geranylgeraniol (C1) and 6α, 7β-dihydroxyvouacapan-17β-oate methyl ester (C2) isolated from Pterodon pubescens Benth. to the antinociceptive activity of the crude extract.
Compounds C1 and C2 demonstrated activity against writhing with intraperitoneal (i.p.) and oral (p.o.) routes, capsaicin (i.p. and p.o.), glutamate (i.p.), and in the hot-plate (p.o.) tests, demonstrating their contribution to the antinociceptive activity of crude Pterodon pubescens Benth extracts. The observed activity of compounds C1 and C2 may be related to vanilloid receptors VR1, and/or glutamate peripheral receptors. In hot-plate model, the antinociceptive activity was maintained when naloxone chloride (opioid antagonist) was administered prior to treatment with compounds suggesting that C1 and C2 (p.o.) do not exert their antinociceptive effects in the hot-plate test via opioid receptors. The findings presented herein also suggest that compounds within the crude Pterodon pubescens Benth. extract may exert a synergistic interactive effect, since the crude extract (300 containing lower concentrations of compounds C1 (11.5%- 34.6 mg. kg-1) and C2 (1.5% - 4.7 gave statistically the same effect to the pure compounds when tested separately (C1 = C2 = 300 in writhing experimental model with p.o. administration. Further studies will be undertaken to establish more specifically the mechanisms of action for compounds C1 and C2. Possible synergistic interactions will be evaluated employing the Isobole method.
These results allowed us to establish a relationship between the popular use of Pterodon pubescens seeds for pain relief and the activity of two major compounds isolated from this species which demonstrated antinociceptive activity. Various "in vivo" experimental models corroborate the folk use of this species for different pain and inflammation disorders.
PMCID: PMC2817697  PMID: 20055987
22.  Antinociceptive and Toxicological Effects of Dioclea grandiflora Seed Pod in Mice 
The acute treatment of mice with an ethanolic extract from the seed pod of Dioclea grandiflora (EDgP) at doses of 75, 150 and 300 mg/kg by intraperitoneal administration produced a significant antinociceptive effect as displayed by the acetic acid-induced writhing test and the formalin test. The antinociception was observed through the first (neurogenic pain) and second (inflammatory pain) phases in the formalin test. The hot plate test did not show an increase in the antinociceptive latency whereas the motor performance was affected by the administration at 300 mg/kg at the beginning (30 minutes) of the observation period but not at later periods (60 and 120 minutes). These results suggest that EDgP has a central antinociceptive action and a possible anti-inflammatory activity in mice.
PMCID: PMC2846350  PMID: 20368784
23.  Antinociceptive Activity of Trichilia catigua Hydroalcoholic Extract: New Evidence on Its Dopaminergic Effects 
Trichilia catigua is a native plant of Brazil; its barks are used by some local pharmaceutical companies to prepare tonic drinks, such as Catuama. The present study was addressed to evaluate the effects of T. catigua hydroalcoholic extract in mouse nociception behavioral models, and to evaluate the possible mechanisms involved in its actions. Male Swiss mice were submitted to hot-plate, writhing and von Frey tests, after oral treatment with T. catigua extract (200 mg kg−1, p.o.). The extract displayed antinociceptive effect in all three models. For characterization of the mechanisms involved in the antinociceptive action of the extract, the following pharmacological treatments were done: naloxone (2.5 mg kg−1, s.c.), SR141716A (10 mg kg−1, i.p.), SCH23390 (15 μg kg−1, i.p.), sulpiride (50 mg kg−1, i.p.), prazosin (1 mg kg−1, i.p.), bicuculline (1 mg kg−1, i.p.) or dl-p-chlorophenylalanine methyl ester (PCPA, 100 mg kg−1, i.p.). In these experiments, the action of T. catigua extract was evaluated in the hot-plate test. The treatment with SCH23390 completely prevented the antinociceptive effect, while naloxone partially prevented it. The possible involvement of the dopaminergic system in the actions of T. catigua extract was substantiated by data showing the potentiation of apomorphine-induced hypothermia and by the prevention of haloperidol-induced catalepsy. In conclusion, the antinociceptive effects of T. catigua extract seem to be mainly associated with the activation of dopaminergic system and, to a lesser extent, through interaction with opioid pathway.
PMCID: PMC3095233  PMID: 19815648
24.  The antinociceptive effect of 4-substituted derivatives of 5-(4-chlorophenyl)-2-(morpholin-4-ylmethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione in mice 
The aim of the present experiments was to examine the antinociceptive activity of 4-substituted derivatives of 5-(4-chlorophenyl)-2-(morpholin-4-ylmethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione in mice. The compounds were synthesized using the so-called Mannich reaction and their structures were confirmed using IR and 1H-NMR spectra. The antinociceptive activity was investigated in two behavioral tests: the hot plate test and the writhing test. For preliminary estimation of other behavioral effects, the locomotor activity of mice, the motor coordination in the rota-rod test, and the myorelaxation in the chimney test were also studied. The changes in body temperature of animals were also recorded. We demonstrated that all examined compounds produced antinociceptive effect, both in the hot plate test and in the writhing test, without impact on the motor coordination and myorelaxation of animals. The pharmacological effect of all drugs has been developed within 60 min after administration of drugs; and in two cases (T-103 and T-104), it has been a short-lasting effect (up to 90 min). Two compounds (T-100 and T-102) also inhibited the locomotor activity of animals. T-104 induced the changes in body temperature of mice. Generally, we demonstrated that combination of two different heterocyclic systems (morpholine and 1,2,4-triazole) might be beneficial for reduction of nociception.
PMCID: PMC3964309  PMID: 24326964
Antinociceptive activity; The hot plate test; The writhing test; Behavioral tests
25.  Involvement of opioid and monoaminergic pain pathways in Aegle marmelos induced analgesia in mice 
Indian Journal of Pharmacology  2013;45(4):371-375.
To study analgesic activity and to evaluate the involvement of opioid and monoamines in the antinociceptive activity of methanol extract of leaves of Aegle marmelos.
Materials and Methods:
Analgesic activity of methanol extract (ME) of A. marmelos alone (75,150 and 300mg/kg orally) and in combination with morphine or venlafaxine (subanalgesic) were studied using tail flick test and acetic acid-induced writhing in mice. The effect of pre-treatment with opioid antagonist naltrexone 1mg/kg was also studied on antinociception induced due to ME.
ME produced a dose-dependent significant antinociceptive activity in the tail flick test and acetic acid-induced writhing in mice. (P<0.05) Administration of subanalgesic dose of ME with morphine or venlafaxine also resulted in significant (P<0.05) antinociceptive activity in both the pain models. Pre-treatment with naltrexone inhibited analgesic activity induced by ME alone and combination with morphine or venlafaxine.
A.marmelos in induced antinociception is mediated through both opioid and monoaminergic pain pathways, suggest its possible use in chronic pain.
PMCID: PMC3757606  PMID: 24014913
Aegle marmelos; analgesia; monoamines; opioid; tail flick latency

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