Formalin-induced Hind Paw Licking Research Articles

Heteroaromatic salvinorin A analogue (P-3 l) elicits antinociceptive and anxiolytic-like effects

Previous studies have attributed the prominent analgesic, hallucinogenic, sedative, and anxiolytic properties of Salvia divinorum to Salvinorin A. However, the overall pharmacological profile of this isolate limits its clinical applications. To address these limitations, our study evaluates the C(22)-fused-heteroaromatic analogue of salvinorin A [2-O-salvinorin B benzofuran-2-carboxylate] (P-3l) in mice nociception and anxiety models while assessing possible mechanism of action. In comparison with the control group, orally administered P-3l (1, 3, 10, and 30 mg/kg) attenuates acetic acid-induced abdominal writhing, formalin-induced hind paw licking, the thermal reaction to the hotplate, and/or aversive response in the elevated plus-maze, open field, and light-dark box; and potentiates the effect of morphine and diazepam at sub-effective doses (1.25 and 0.25 mg/kg, respectively) without eliciting significant alterations in relative organ weight, or haematological or biochemical parameters. The in vivo blockade of P-3 l effects by naloxone (non-selective opioid receptor antagonist), naloxonazine (antagonist of specific subtypes mu1 of μ-OR), and nor-binaltorphimine (selective ĸ-OR antagonist) supports initial results from binding assays and the interpretations made possible from computational modeling of the interactions of P-3 l with the opioid receptor subtypes. In addition to the opioidergic mechanism, the blockade of the P-3 l effect by flumazenil suggests benzodiazepine binding site involvement in its biological activities. These results support P-3 l potentially possessing clinical utility and substantiate the need for additional pharmacological characterization.

Analgesic Activity of Methanol Leaf Extract of Tamarindus Indica Plant in Mice and Rats

Tamarindus indica has several folkloric uses in the treatment of various ailments. This study evaluated the analgesic activity of methanol leaf extract of Tamarindus indica (MLETI) in mice and Wistar rats. Acute toxicity studies were conducted using both the modified method of Lorke and OECD 425 guidelines. The analgesic activity was tested using acetic acid-induced writhing test, hot plate and formalin-induced hind-paw licking. Glycosides, flavonoids, saponins, alkaloids, reducing sugars, steroids and terpenoids were identified from the MLETI following phytochemical analysis. The LD50 was above 5000 mg/kg in both species. Compared to controls, the MLETI (50, 100, and 200 mg/kg) produced significant (p<0.001) dose-dependent reductions (33.6%, 35.5% and 47.2%) in acetic acid-induced writhes in the treated mice. MLETI also produced significant (p<0.005) analgesic effect with the hot plate-induced pain and significantly (p<0.001) inhibited formalin-induced paw-licking response in test rats compared to controls. This was higher in the second phase compared to the early phase at all the tested doses. The methanol leaf extract of Tamarindus indica possesses analgesic activity. It also contained glycosides, flavonoids, saponins, alkaloids, reducing sugars, steroids and terpenoids, some/all of which may be responsible for the observed centrally and peripherally mediated analgesic activities.
 Keyword: Analgesic, Fabaceae, mice, Tamarindus indica, Wistar rats

Antipyretic and anti-nociceptive effects of methanol extract of leaves of Fimbristylis miliacea in mice model

Ethnopharmacological relevanceFimbristylis miliacea (L.) Vahl (Cyperaceae) is a grass like herb usually grows as a weed in rice fields and is mainly distributed in tropical or sub-tropical countries of south and south-east Asia, central America, northern Australia and west Africa. The plant has been traditionally used to treat fever as a form of poultice. Aim of the studyThe present study aimed to investigate antipyretic and anti-nociceptive effects of methanol extract of leaves of Fimbristylis miliacea in mice model. Materials and methodsAntipyretic effect of Fimbristylis miliacea was examined using Baker's yeast induced hyperthermia test. Anti-nociceptive effect was investigated using acetic acid induced writhing test, formalin induced hind paw licking test and hot plate test. ResultsThe extract at concentration of 400 mg/kg produced significant reduction in body temperature after 0.5 h of administration (4.12 °F, p ≤ 0.001) and continued to decrease (after 4 h, 5.92 °F, p ≤ 0.001). Extracts at 100 mg/kg and 200 mg/kg decreased the temperature by about 2.77 °F (from 99.47 °F to 96.7 °F) and 5.58 °F (98.2 °F–92.62 °F) respectively after 4 h whereas paracetamol dropped by about 7.2 °F (p ≤ 0.001). The extract showed significant decrease in number of writhes at all concentrations. Highest effect was found at 200 mg/kg having 35.7 writhes (p ≤ 0.001), much lower than control (89.2); standard drug diclofenac showed 23.2 writhes. Percent inhibition of writhing were 54.26 and 73.99 for 200 mg/kg and diclofenac respectively. The result of hind paw licking test also corroborated writhing test. Significant reduction in percent inhibition of licking was observed mainly in late phase. Percent inhibition of licking were 93.77 and 51.55 for 400 mg/kg extract and diclofenac respectively. In hot plate test, extract at 400 mg/kg showed significant increase in latency from 10.77 s to 13.59 s (p ≤ 0.05). Extract at this dose after 2 h demonstrated greater percent maximal effect (43.26%) compared to ketorolac (40.19%). ConclusionThe experiment confirmed the traditional use of F. miliacea in the treatment of fever with possible anti-nociceptive effects.

Methanol extract of smokeless tobacco alters inflammation and nociception process in animal models

Purpose: To investigate the inflammatory and nociceptive alterations due to the use of Nicotiana tabacum or smokeless tobacco (MEST) owing to the fact that it is used by some people to relieve dental pain.Methods: Hepatic biochemical indicators and thiobarbituric acid reactive substances assay were used to assess MEST toxicity and pharmacological doses selection. The effects on inflammation of different pharmacological doses (100, 200 and 500 mg/kg i.p.) of MEST were evaluated using xylene-induced ear edema and cotton pellet granuloma tests. Indomethacin (10 mg/kg, i.p.) was used as positive standard drug, whereas the vehicle 0.5 % CMC treated group was considered as negative control. Acetic acid-induced abdominal contraction test and formalin-induced hind paw licking model were utilized to assess the role of MEST in nociception. Indomethacin (10 mg/kg i.p.) and diclofenac sodium (10 mg/kg i.p.) were used as positives standard drugs. The vehicle used was 0.5% CMC which served as the negative control.Results: MEST (50 %, 200 mg/kg) and indomethacin (47.5 %) both elicited a significant (p < 0.001) anti-edematogenic effect on xylene-induced ear edema. MEST also showed a significant (p < 0.001) inhibitory effect on granuloma formation at all administered doses as compared to the untreated groups which was comparable to standard drug indomethacin. The number of acetic acid induced writhings was observed to be significantly increased (p < 0.001) by MEST at all doses, unlike diclofenac that led to significant reduction (p < 0.001) in the number of writhings, when compared to the untreated group. MEST also showed a significant (p < 0.05) dose-dependent reduction of the hind paw licking caused by formalin when compared to the vehicle control.Conclusion: These results signify that administration of MEST induces inflammatory and nociceptive alterations. However, the extract is not recommended for dental pain due to its other toxic effects that have previously been reported.Keywords: Nicotiana tabacum, Smokeless tobacco, Inflammation, Nociception

Methanolic Extract of Peel of Citrus maxima Fruits Exhibit Analgesic, CNS Depressant and Anti-inflammatory Activities in Swiss Albino Mice

Objectives: This study investigates analgesic, CNS depressant and anti-inflammatory activities of crude methanolic extract of Peel of Citrus maxima fruits. Materials and Methods: Methanolic extracts of Citrus maxima peel with different concentration were tested for analgesic activity in mouse model of acetic acid induced writhing and formalin induced licking and biting. Anti-inflammatory effect was tested by carrageenan induced paw edema model and the CNS depressant activity was evaluated by observing the reduction of locomotors activity by hole cross and open field test. Results: The extract, at 500 mg/kg, showed higher analgesic activity (73.34%) against acetic acid induced pain in mice while the standard reference drug Diclofenac sodium exhibited 87.13% activity at 10 mg/kg dose. The test dose at 500 mg/kg produced 48.23% protection in formalin induced hind paw licking and biting compared to 54.11% protection by the reference drug (10 mg/kg Diclofenac sodium). The antiinflammatory effect of the extract was comparable to reference drug Ibuprofen and the effect was sustained for 2-4 hr. However, the extract also showed significant dose dependent CNS depressant activity. Conclusion: Methanolic extract of peel of Citrus maxima fruits has CNS depressant effect with moderate analgesic and anti-inflammatory properties.

Analgesic and anti-inflammatory activities of methanolic extract of Mallotus repandus stem in animal models

The aim of our current study is to investigate the analgesic and anti-inflammatory potentials of methanolic extract of Mallotus repandus stem (MSM) using different in vivo assay models. Analgesic and anti-inflammatory activities were evaluated using acetic acid induced writhing test, tail immersion method, hot-plate test, formalin induced hind paw licking, xylene induced ear edema, carrageenan-induced paw edema and cotton pellet induced granuloma in animal model at doses of 500, 1000 and 2000 mg/kg body weight. MSM showed significant (p < 0.05) analgesic activities in the acetic acid-induced writhing tests in mice. In the tail immersion and hot-plate test, MSM significantly prolonged the latency period (p < 0.05). Significant (p < 0.05) formalin induced paw licking inhibition was observed at different doses and the highest 74.47% inhibition was observed at 2000 mg/kg. Besides, MSM showed significant (p < 0.05) anti-inflammatory responses in carrageenan induced paw edema, xylene induced ear edema and cotton pellet induced granuloma methods. These findings suggest that the plant may be a potential source for the development of new analgesic and anti-inflammatory agent.

An in vivo study regarding analgesic and anxiolytic activity of methanolic extract of Typha elephantina Roxb

BackgroundTypha elephantina Roxb. is a widely scattered grass like medicinal plant in Bangladesh and thus demands biological investigations to discover its therapeutic potentiality. The aim of our present study was to assess analgesic and anxiolytic properties of methanolic extract of Typha elephantina Roxb.MethodsFor evaluating analgesic activity, the methanolic extract was subjected to intraperitoneally (i.p.) administered acetic acid-induced writhing test & subcutaneously administered (s.c.) formalin-induced hind paw licking test in Swiss-albino mice. The anxiolytic activity was conducted by using elevated plus maze (EPM) and hole board models.ResultsFor both methods of analgesic test experimental plant extract was found to have significant (p < 0.001) analgesia at the dose of 200 mg/kg & 400 mg/kg body weight in mice when compared to control, where acetyl salicylic acid (100 mg/kg body weight) was used as standard drug. The percentages of inhibition found in case of acetic acid-induced writhing test were 26.27%, 50.45% and 20.29% respectively for acetyl salicylic acid (100 mg/kg), 200 mg/kg extract dose and 400 mg/kg extract dose. On the other hand, during formalin-induced hind paw licking test, the percentages of inhibition also increased when the extract dose increases from 200 mg/kg to 400 mg/kg by 53.95% to 61.79% at early phase and 71.62% to 78.8% at late phase respectively while acetyl salicylic acid (100 mg/kg), responsible for 25.58% and 38.74% of inhibition at both phase sequentially. Again, the crude extract significantly (p < 0.01; p < 0.001) raised the time spent in the open arm (149.2 ± 27.63** sec) & the number of head-dips (50.00 ± 4.66***) at the dose 400 mg/kg body weight in case anxiolytic test, while reference drug diazepam (1 mg/kg body weight) also exhibited significant (p < 0.01) result in case of time spent in open arm (107.0 ± 12** sec) but not for head dipping (14.83 ± 1.6).ConclusionFindings of the present study assure that Typha elephantina Roxb. may be effective for the treatment of pain and anxiety with the demands of further investigations to isolate the active compound(s).

Antinociceptive and Antioxidant Activities of the Methanolic Extract of Telfairia occidentalis Seeds.

Context:The seeds of Telfairia occidentalis have been known to possess different biological properties and are used in traditional medicine in Africa and Asia to treat many ailments. The plant is particularly noted traditionally for its healing properties and is usually consumed in the form of herbal decoctions/concoctions as a blood tonic, to treat sudden attacks of convulsions, pain, malaria and anaemia.Aims:In the present study, various phytochemical and pharmacological studies were done on the methanolic extract of the seeds of Telfairia occidentalis to evaluate its antioxidant and antinociceptive properties to substantiate its traditional use.Methods:Phytochemical screening of the extract was done according to standard procedures. Antioxidant potential was ascertained using 2,2-diphenyl-1-picryl hydrazyl (DPPH) scavenging activity, total phenolic content and total flavonoid content assays. Analgesic activity was analyzed using formalin induced paw licking test in albino rats at 100, 200 and 400 mg extract per kg body weight.Statistical Analysis Used:All results extrapolated from the experiments were expressed as mean ± SEM. Data obtained was analyzed statistically using ANOVA (one-way) followed by Dennett's posthoc test.Results:Phytochemicals present in the extract were alkaloids, flavonoids, saponins, terpenoids, steroid and anthraquinones. The extract significantly inhibited DPPH scavenging activity with percentage inhibition of 147.3%. The methanolic seed extract of T. occidentalis significantly reduced (P < 0.05) formalin induced paw licking in both neurogenic and inflammatory phases of formalin induced paw licking test, with 35.59 and 78.51% inhibition at 400 mg/kg, in albino rats in a dose dependent manner.Conclusions:The seed extract in this study significantly reduced formalin induced hind paw licking, and could be used as an analgesic for treatment of pain and also showed marked antioxidant potential.

Investigations of Analgesic Activity of the Methanol Extract of Haldina cordifolia (Roxb.) Bark by using in vivo Animal Model Studies

The present study was to investigate the analgesic activity of the methanol extract of H. cordifolia bark by using in vivo animal model studies. The effect was studied using acetic acid-induced abdominal constriction test and formalin induced hind paw licking test in mice model. The results of the study showed that the extract exhibited significant analgesic effect. In acetic acid-induced writhing test, significant percentage of inhibition (78.48%) shows that at the dose of 400 mg kgG 1 and at the same dose in formalin induced hand paw licking model shows significant activity in early phase (22.03% of inhibition) where in late phase (19.88% of inhibition) comparable to standard drug diclofenac sodium. These findings suggested that H. cordifolia bark has got the potential as a candidate for future analgesic agent.

Synthesis and biological evaluation of some novel 1-substituted fentanyl analogs in Swiss albino mice.

Fentanyl [N-(1-phenethyl-4-piperidinyl)propionanilide] is a potent opioid analgesic agent, but a has narrow therapeutic index. We reported earlier on the synthesis and bioefficacy of fentanyl and its 1-substituted analogs (1–4) in mice. Here we report the synthesis and biological evaluation of four additional analogs, viz. N-isopropyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (5), N-t-butyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (6), isopropyl 2-[4-(N-phenylpropionamido)piperidin-1-yl]propionate (7) and t-butyl 2-[4-(N-phenylpropionamido)piperidin-1-yl]propionate (8). The median lethal dose (LD50) determined by intravenous, intraperitoneal and oral routes suggests these analogs to be comparatively less toxic than fentanyl. On the basis of observational assessment on spontaneous activities of the central, peripheral, and autonomic nervous systems, all the analogs were found to be similar to fentanyl. Naloxone hydrochloride abolished the neurotoxic effects of these analogs, thereby ascertaining their opioid receptor-mediated effects. All the analogs displayed significant analgesic effects, measured by formalin-induced hind paw licking and tail immersion tests at their respective median effective dose (ED50). They also exhibited 8–12 fold increase in therapeutic index over fentanyl. However, 5 and 6 alone produced lower ED50 (20.5 and 21.0 µg/kg, respectively) and higher potency ratio (1.37 and 1.33, respectively) compared to fentanyl. They could thus be considered for further studies on pain management.

Anti-Inflammatory and Anti-Nociceptive Activities of Methanol Extract from Aerial Part of Phlomis younghusbandii Mukerjee

This study was designed to investigate the anti-inflammatory and anti-nociceptive activity of the methanol extract from the aerial part of Phlomis younghusbandii (MEAP) and to explore the possible related mechanisms. Anti-inflammatory effects of MEAP were evaluated by using the ear edema test induced by dimethylbenzene and vascular permeability test induced by acetic acid. Anti-nociceptive activities of MEAP were evaluated by the chemical nociception in models of acetic acid-induced writhing and formalin-induced hind paw licking, and by the thermal nociception in hot plate tests. Mechanisms of MEAP activities also were explored by evaluating expression levels of TNF-α, IL-6 and iNOS induced by LPS using real-time fluorogenic PCR and expression of COX-2 using Western blotting and an open-field test. The results indicated that the MEAP administered orally could significantly decrease ear edema induced by dimethylbenzene and increase vascular permeability induced by acetic acid. Additionally, the nociceptions induced by acetic acid and formalin were significantly inhibited. The anti-nociceptive effect could not be decreased by naloxone in the formalin test, and MEAP did not affect the normal autonomic activities of mice. Expression levels of pro-inflammatory cytokines (TNF-α, IL-6, iNOS) induced by LPS were decreased obviously by treatment with MEAP. Furthermore, COX-2 expression in the spinal dorsal horns of the pain model mice induced by formalin was significantly down-regulated by MEAP. In conclusion, MEAP has significant anti-inflammatory and antinociceptive activities, and the mechanisms may be related to the down-regulated expression of TNF-α, IL-6, iNOS and COX-2.

Evaluation of antinociceptive activity of Ajuga bracteosa wall ex benth

Objective: The present study was aimed to investigate the in vivo anti‑nociceptive activity of Neelkanthi (whole plant) and to support its traditional use. Materials and Methods: Methanolic extract of plant Ajuga bracteosa (ABE) was investigated for its anti‑nociceptive activity in hot‑plate method, tail flick method and formalin induced hind paw licking test in mice. Three doses of the extract (ABE ‑ 250 mg/kg, 500 mg/kg and 750 mg/kg, i.p.) were used in the study and codeine (5 mg/kg, i.p.) was used as standard. Results: ABE (500 mg/kg and 750 mg/kg, i.p.) significantly (P < 0.05) increased the reaction time in both hot plate method and tail flick method. ABE also showed significant decrease in the paw licking response in formalin induced hind paw licking test in mice. Conclusions: ABE at the dose of 500 mg/kg and 750 mg/kg showed potent anti‑nociceptive activity on comparison with the standard drug and supported its traditional use as analgesic. Key words: Anti‑nociceptive, codeine, formalin, tail‑flick

Analgesic activity of the ethanolic extract of Shorea robusta resin in experimental animals

Aim:Shorea robusta (Sal), an important traditional Indian medicinal plant used in various ailments and rituals and the indigenous use of the resin of this plant as a medicament for treatment of various inflammatory conditions is well documented in literature. In the present study, ethanolic extract of S. robusta resin (SRE) was evaluated for its analgesic activity by making use of different central and peripheral pain models.Materials and Methods:The analgesic activity of SRE was assessed by employing different pain models such as, i) hot plate and tail flick tests for central analgesia, ii) acetic acid- induced writhing (peripheral analgesic model), iii) formalin-induced hind paw licking (both central and peripheral model), iv) carrageenan-induced hyperalgesia (peripheral analgesic model) and v) post-surgical pain (peripheral analgesic model).Results:The extract produced significant central and peripheral analgesic effects, as is evident from increase in reaction time in hot plate and tail flick tests, inhibition in writhing counts in acetic acid-induced writhing test, inhibition of licking time in formalin-induced hind paw licking, increased pain threshold in paw withdrawal latency in carrageenan-induced hyperalgesia and increased paw withdrawal threshold in post-surgical pain.Conclusion:The results of the present study demonstrate marked antinociceptive effects of SRE.

Anti-nociceptive effects of Carpolobia lutea G. Don (Polygalaceae) leaf fractions in animal models

Leaves from Carpolobia lutea (Polygalaceae) were screened to establish the antiulcer ethnomedicinal claim and to quantitatively isolate, elucidate the active compounds by semi-preparative HPLC. The anti-nociceptive effects of Carpolobia lutea (CL) G. Don (Polygalaceae) organic leaf extracts were tested in experimental models in mice. The anti-nociceptive mechanism was determined using tail-flick test, acetic acid-induced abdominal constrictions, formalin-induced hind paw licking and the hot plate test. The fractions (ethanol, ethyl acetate, chloroform, n-hexane) and crude ethyl acetate extract of CL (770mg/kg, i.p.) produced significant inhibitions of both phases of the formalin-induced pain in mice, a reduction in acetic acid-induced writhing as well as and an elevation of the pain threshold in the hot plate test in mice. The inhibitions were greater to those produced by indomethacin (5mg/kg, i.p.). Ethyl acetate fraction revealed cinnamic and coumaric acids derivatives, which are described for the first time in literature. These cinnamalglucosides polyphenols characterised from CL may in part account for the pharmacological activities. These findings confirm its ethnomedical use in anti-inflammatory pain and in pains from gastric ulcer-associated symptoms.

S41744, a dual neurokinin (NK)1 receptor antagonist and serotonin (5-HT) reuptake inhibitor with potential antidepressant properties: A comparison to aprepitant (MK869) and paroxetine

Though neurokinin(1) (NK(1)) receptors are implicated in depressed states and their treatment, selective antagonists have disappointed in clinical trials. Accordingly, we designed a novel ligand, S41744 (2-piperazin-1-yl-indan-2-carboxylic-acid-(3-chloro-5-fluoro-benzyl)-methyl-amide), which both blocks NK(1) receptors and interferes with serotonin (5-HT) reuptake. S41744 mimicked the selective antagonist aprepitant in binding human (h)NK(1) receptors and in antagonising Substance-P-mediated Extracellular-Regulated-Kinase phosphorylation (pK(B), 7.7). Further, it dose-dependently (0.63-40.0 mg/kg, i.p.) displaced ex vivo [(3)H]-[Sar(9),Met(O(2))(11)]-Substance P binding to gerbil striatum, attenuated formalin-induced hind-paw licking in gerbils, and antagonised locomotion induced by i.c.v. administration of the NK(1) agonist GR73632 to guinea pigs. Like paroxetine, S41744 recognised h5-HT transporters, reduced synaptosomal uptake of 5-HT (pK(B), 7.9), and dose-dependently (0.63-10.0 mg/kg) elevated dialysis levels of 5-HT in the hippocampus and frontal cortex of freely-moving guinea pigs. Further, S41744 increased extracellular levels of 5-HT in frontal cortex and hippocampus of rats to a greater extent than paroxetine, and its inhibitory influence upon serotonergic perikarya was blunted relative to its affinity for 5-HT transporters. S41744 more potently blocked stress-induced vocalizations in guinea pigs than aprepitant and paroxetine, and it was active in forced-swim and marble-burying procedures of putative antidepressant properties in mice. While aprepitant displayed anxiolytic actions in stress-induced foot-tapping and social interaction tests in gerbils, paroxetine was anxiogenic and S41744 "neutral", reflecting balanced NK(1) antagonism and suppression of 5-HT reuptake. Moreover, S41744 shared anxiolytic actions of aprepitant in the rat Vogel Conflict Test. In conclusion, S41744 is an innovative NK(1) antagonist/5-HT reuptake inhibitor justifying further evaluation for treatment of stress-related disorders.

Analgesic and anti-inflammatory activity of amifostine, DRDE-07, and their analogs, in mice.

Objectives:To find out the analgesic and anti-inflammatory activity, if any, of Amifostine [S-2(3 amino propyl amino) ethyl phosphorothioate], DRDE-07 [S-2(3 amino ethyl amino) ethyl phenyl sulphide] and their analogs DRDE-30 and DRDE-35, the probable prophylactic agent for sulphur mustard (SM).Materials and Methods:In order to find out the analgesic activities of the compounds two methods were employed, namely, acetic acid-induced writhing test and formalin-induced paw licking. The persistent pain model of formalin-induced hind paw licking was carried out to test the effect of the compounds on neurogenic pain or early phase (0 to 5 minutes) and on the peripheral pain or the late phase (15 to 30 minutes). To test the effect of the compound in acute inflammation, carrageenan-induced hind paw edema was carried out. This model of inflammation involves a variety of mediators of inflammation.Results:DRDE-07 (81.7%) and DRDE-30 (79.4%) showed significant reduction in the acetic acid-induced writhing test. DRDE-07 (93.1%), DRDE-30 (82%), and DRDE-35 (61.3%) showed significant reduction in the second or late phase of formalin-induced paw licking. All the analogs (more than 60%) including amifostine (43.9%) showed significant reduction of paw edema in the carrageenan-induced paw edema in mice.Conclusion:The analgesic and anti-inflammatory activity of the antidotes were comparable with aspirin.

Antipyretic and analgesic activities ofCaesalpinia bonducella seed kernel extract

Ethanolic extract (70%) of Caesalpinia bonducella seed kernel has been subjected for its antipyretic and antinociceptive activities in adult albino rats or mice of either sex at 30, 100 and 300 mg/kg orally. The extract demonstrated marked antipyretic activity against Brewer's yeast-induced pyrexia in rats. The extract had significant central analgesic activity in hot plate and tail flick methods. It also exhibited marked peripheral analgesic effect in both acetic acid-induced writhing test in mice and Randall-Selitto assay in rats. It also significantly inhibited the formalin-induced hind paw licking in mice. In conclusion, the present study suggests that the ethanolic extract of Caesalpinia bonducella seed kernel possesses potent antipyretic and antinociceptive activities and thus, validates its use in the treatment of pain and pyretic disorders.

Hypericum triquetrifolium Turra. extract exhibits antinociceptive activity in the mouse

The aim of the present study was to investigate the antinociceptive activity of Hypericum triquetrifolium Turra. extract. The lyophilized extract was administered to male Swiss mice. Formalin paw test and tail flick tests were used for the evaluation of the antinociceptive activity. Plant extract (10, 25, 50 and 60 mg kg −1, i.p.) ( n=16–24 for each group) or vehicle ( n=27) was administered 30 min before the subplantar formalin injection. In the tail flick test, mice were examined for latency to withdraw their tails from a noxious thermal stimulus using a tail flick meter ( n=8 for each group). The effects of the extract on sensorimotor performance was also assessed ( n=16–24 for each group). The extract caused a significant dose-related inhibition of the first phase (50, 60 mg kg −1, i.p.) and second phase (10, 25, 50 and 60 mg kg −1, i.p.) of formalin induced hindpaw licking. Additionally, the extract administration (50, 60 mg kg −1, i.p.) increased the tail flick latencies. No significant change was observed in any of the treatment groups in the sensorimotor performance test. The observed antinociceptive activity of the extract may be due to its noradrenaline and serotonin reuptake blocking activity. Moreover, the probable antiinflammatory activity of the extract may play a role in the dose-related inhibition of the second phase of formalin paw test.

Hyperalgesia in mice lacking the Kv1.1 potassium channel gene

Hyperalgesia and morphine induced antinociception were measured in mice lacking the gene for the Shaker-like voltage-gated potassium channel Kv1.1 alpha subunit. The effects of varying gene dosage were studied by comparing homozygous null (−/−) versus heterozygous (±) and wildtype (+/+) littermates. Hyperalgesia was measured using the paw flick assay, hot plate assay and formalin induced hind paw licking. It was observed that null mutant animals had significantly shorter latencies to response in the paw flick (36%) and hot plate (27%) assays while their licking times after hind paw injection of formalin was increased in both the first (74%) and second (65%) phases of the response compared to wildtype controls. Morphine induced antinociception in Kv1.1 null mutant animals was blunted. These studies indicate that Kv1.1 plays an important role in nociceptive and antinociceptive signaling pathways.

Inhibition of nitric oxide synthase by isothioureas: Cardiovascular and antinociceptive effects

A range of substituted isothiourea compounds including S-isopropylisothiourea (IPTU), S-methylisothiourea (SMT), S-ethylisothiourea (ETU), N-pentylisothiourea (PTU), S-(2 aminoethyl)isothiourea (AETU), and S-acetamidoisothiourea (AATU) inhibit mouse spinal cord/cerebellar neuronal nitric oxide synthase (nNOS) and bovine aortic endothelial cell eNOS in vitro. IP administration of isothioureas increased mean arterial blood pressure of the urethane-anaesthetised mouse (rank order of effect: IPTU > ETU > SMT > AETU). PTU and AATU were without vasopressor activity. IPTU (50 mg/kg, IP) inhibited late phase formalin-induced hindpaw licking behaviour in the mouse while SMT (50 mg/kg, IP) was without effect. Neither compound influenced the formalin-induced increase in hindpaw weight reflecting a lack of significant peripheral antioedema effect in this model. IPTU (50 mg/kg, IP) but not SMT (50 mg/kg, IP) inhibited mouse spinal cord and cerebellar NOS activity measured ex vivo in animals killed 45 min after injection. The present study confirms the potent NOS inhibitory effect of selected substituted isothioureas in vitro. Little or no isoform selectivity (i.e., nNOS vs. eNOS) was apparent. The potent vasopressor effect of isothioureas indicates that these compounds may be of limited use as tools to study the role of nitric oxide in pain perception.