Analgesic Activity In Mice Research Articles

To Evaluate and Compare the Analgesic Activity of Piperine and Extracts of Piper Nigrum L. Fruit

Narcotics (e.g., opioids) or non-narcotics (e.g., salicylates and corticosteroids) are used in the management of pain and inflammation, both of which have side effects, thereby emphasizing the search for natural substances. Piperine found naturally in plants of the Piperaceae family has shown inhibitory activity against 5-lipoxygenase and cycloxygenase-1 in in vitro studies. The present study was aimed to evaluate and compare the analgesic activity of pure compound, piperine along with hexane and ethanol extracts of Piper nigrum L. fruit in mice. The analgesic activity was determined by hot plate, tail immersion method and acetic acid induced writhing test in mice. The piperine showed great pain-relieving impact at a portion of 5 and 10 mg/kg when contrasted with control and standard. Greatest pain-relieving impact was noted at a portion of 10 mg/kg after 120 min. The hexane and ethanol remove demonstrated helpless pain-relieving impact at all dosages (5, 10 and 20 mg/kg) by hot plate method. However, with tail immersion method, piperine at a dose of 5mg/kg and ethanol extract at a dose of 20mg/kg after 120 min and hexane extract at a dose of 10mg/kg after 60min exhibited significant analgesic activity. In writhing test ethanol extract significantly stopped the number of writhes at dose of 20mg/kg while piperine at dose of 20mg/kg completely terminated the writhes in mice. It is concluded from the present study that Piper nigrum L. possesses potent analgesic activity in mice. Keywords: Piper nigrum, Piperaceae, Piperine, Hot plate, Tail immersion method, Acetic acid induced writhing test

Evaluation of Analgesic, Anti-inflammatory and Antipyretic activities of the Methanol Extract of Crinum jagus Bulb in Rats

This study evaluated the analgesic, anti-inflammatory and antipyretic activities of the methanol extract of Crinum jagus bulb. The preliminary phytochemical analysis and acute toxicity studies were carried out following standard procedures. Assessment of analgesic activity in mice was performed using acetic acid-induced writhing and formalin-induced pain tests. Anti-inflammatory and antipyretic activities were performed in rats using egg albumin-induced pedal oedema and Brewer’s yeast-induced pyrexia models respectively. The results of the qualitative phytochemical analysis revealed that the bulb contained alkaloids, flavonoids, steroids, saponins, phenols and terpenoids. The extract was non-toxic; the oral LD was greater than 5000 mgkg-1 at 24 h. The 50 maximal analgesic effect of the extract against acetic acid-induced pain was 47.2% at 400 mgkg-1 compared to 82.2% with aspirin (50 mgkg-1). The extract exerted no significant (p>0.05) analgesic effect different from the control in the first phase (5 min) of formalin-induced pain test. However, there was dose dependent inhibition of pain sensitivity which peaked 85% at 400 mg/kg compared to 94% with piroxicam (500 mgkg-1) in the second phase (15-30 min) of the test indicating a peripherally mediated effect. The lowest test dose (100 mgkg-1) of extract had a comparable oedema inhibition (20%) to aspirin (50 mg/kg). C. jagus bulb extract produced a maximal antipyretic potency (79.5%) at 100 mgkg-1 compared to 83% with paracetamol (50 mgkg-1). Crinum jagus bulb could be a source of potent compounds against pain, inflammation and fever.

Corydalis tomentella Franch. Exerts anti-inflammatory and analgesic effects by regulating the calcium signaling pathway

Ethnopharmacological relevanceCorydalis tomentella Franch. is a perennial cespitose plant commonly used to treat stomachaches as a folk medicine. The C. tomentella total alkaloids have good protective effects against acute liver injury and potential anti-hepatoma and anti-Alzheimer's disease activities. Aim of the studyTo establish an effective purification process for total alkaloids from C. tomentella and investigate the mechanism of their anti-inflammatory effects. Materials and methodsCorydalis tomentella were purified using macroporous resin. Then the crude and purified C. tomentella extracts (cCTE and pCTE) were qualitatively analyzed using UPLC-Triple-TOF-MS/MS. The cCTE and pCTE were used to investigate and compare their anti-inflammatory effects on lipopolysaccharide (LPS)-induced RAW264.7 cells. Doses at 100, 200 and 400 mg/kg/d of pCTE were used to study their anti-inflammatory and analgesic activities in mice with xylene-induced ear swelling and acetic acid-induced writhing tests. Content of nitric oxide (NO), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were determined both in RAW264.7 cells and mice. Network pharmacology was used to predict the anti-inflammatory mechanism of C. tomentella, and the key enzymes were validated using qPCR and Western Blot analysis. Concentration of intracellular Ca2+ was detected using flow cytometric analysis. ResultsThe C. tomentella total alkaloid purity increased from 6.29% to 47.34% under optimal purification conditions. A total of 54 alkaloids were identified from CTE. Both cCTE and pCTE could suppress the LPS-induced production of NO, IL-6, IL-1β, and TNF-α in RAW264.7 cells. The pCTE exhibited a more potent anti-inflammatory effect; it also inhibited pain induced by xylene and acetic acid in mice. The calcium signaling pathway is associated with the anti-inflammatory and analgesic activities of C. tomentella. The mRNA expression of nitric oxide synthase (NOS) 2, NOS3 and calmodulin1 (CALM1) was regulated by C. tomentella through the reduction of inflammation-induced Ca2+ influx, and it also exhibited a more pronounced effect than the positive control (L-NG-nitro arginine methyl ester). ConclusionsPurified C. tomentella extract shows anti-inflammatory effect both in vitro and in vivo. It exerts anti-inflammatory and analgesic effects through the calcium signaling pathway by down-regulating NOS2 and CALM1 expression and up-regulating NOS3 expression in LPS-induced RAW264.7 cells, and decreasing intracellular Ca2+ concentration.

Characterizations of the active ingredients of methanol extract of weaver ant and its analgesic activity in mice

Characterizations of the active ingredients of methanol extract of weaver ant and its analgesic activity in mice

Study on the Analgesic Activity of Peptide from Conus achates.

As a peptide originally discovered from Conus achates by mass spectrometry and cDNA sequencing, Ac6.4 contains 25 amino acid residues and three disulfide bridges. Our previous study found that this peptide possesses 80% similarity to MVIIA by BLAST and that MVIIA is a potent and selective blocker of N-type voltage-sensitive calcium channels in neurons. To recognize the target protein and analgesic activity of Ac6.4 from Conus achates. In the present study, we synthesized Ac6.4, expressed the Trx-Ac6.4 fusion protein, tested Ac6.4 for its inhibitory activity against Cav2.2 in CHO cells and investigated Ac6.4 and Trx-Ac6.4 for their analgesic activities in mice. Data revealed that Ac6.4 had strong inhibitory activity against Cav2.2 (IC50 = 43.6 nM). After intracranial administration of Ac6.4 (5, 10, 20 μg/kg) and Trx-Ac6.4 (20, 40, 80 μg/kg), significant analgesia was observed. The analgesic effects (elevated pain thresholds) were dose-dependent. This study expands our knowledge of the peptide Ac6.4 and provides new possibilities for developing Cav2.2 inhibitors and analgesic drugs.

Preparation and characterization of naproxen solid dispersion using different hydrophilic carriers and in-vivo evaluation of its analgesic activity in mice

BackgroundSolid dispersion (SD) has been used conventionally as a successful technique for improving the dissolution profile and bioavailability of poorly water-soluble drugs. The aim of this study was to progress the dissolution rate and bioavailability of naproxen (BCS class II) by SD technique. Materials & methodsIn this study, hydrophilic carriers are used for preparing solid dispersion of naproxen by evaporation method. The prepared optimized SDNs were evaluated by in-vitro drug dissolution test, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The in-vivo analgesic effects tests of the optimized SDNs (SDN-2 and SDN-5) were performed by tail immersion method and writhing method. ResultsAll the prepared SDNs exhibited a significant increase in the dissolution of naproxen compared to that of the pure drug. Among them, SDN-2 (the dispersion with sodium starch glycolate at 1:2 ratio of naproxen and sodium starch glycolate) and SDN-5 (using the combination of PEG-8000 and sodium starch glycolate with naproxen at 1:1:1 ratio) showed faster dissolution rate as compared to other solid dispersions (SDNs) and pure naproxen. SDN-2 showed 5.4 times better dissolution rate and SDN-5 depicted 6.5-fold increment of dissolution rate compared to pure naproxen drug. DSC, PXRD and SEM microscopy showed that the drugs crystallinity was decreased during the preparation process. FTIR study revealed that naproxen was stable in polymeric dispersions and there was no interaction among the drug and polymers. In writhing method, the percentage inhibition of the number of writhes showed significantly greater (p < 0.01), (p < 0.0001) analgesic activity for the higher dose treatment groups SDN-2(H), and SDN-5(H), respectively, when contrasted to the pure drug naproxen. For tail immersion test, there is increase in latency time at 90 min which is significantly greater (P < 0.01), (P < 0.05), (P < 0.01) for treatment groups SDN-2(H), SDN-5(L), and SDN-5(H), respectively that ultimately authenticates that the optimized SDNs (SDN-2, SDN-5) showed better analgesic activity in mice in comparison with the pure drug. ConclusionIt can be concluded that dissolution of the naproxen could be improved by the making solid dispersion using sodium starch glycolate and/or combination of sodium starch glycolate and PEG 8000 due to the complete transformation of drug into amorphous form with the entire loss of crystallinity, as evidenced by DSC, PXRD, and SEM and also consequences the enhanced analgesic activity in mice.

Evaluation of the analgesic activity of quercetin and chrysin in animal models

Pain is relieved by analgesics that acts via modulating the central and peripheral pain mediators. Some of the analgesic has been reported to have a serious adverse effects when used in long-term treatments. Therefore, there is a need of developing a potent analgesic with minimal of no adverse effects. In the current study, quercetin and chrysin were evaluated for the analgesic activity in mice and rat by hyperalgesia (Eddy’s hot plate and Tail flick analgesiometer). Diclofenac and tramadol was used as a standard reference drugs. Male Swiss Albino mice and rats are divided into six groups and treated with vehicle (1% acacia), quercetin (40 mg/kg), chrysin (100 mg/kg), chrysin (200 mg/kg), diclofenac (10 mg/kg) and tramadol (10 mg/kg) orally. In the present study, diclofenac, tramadol, quercetin and chrysin significantly increased the tail flick latency in the tail flick pain model compared to control group. Chrysin showed remarkable analgesic activity at 200 mg/kg compared to 100 mg/kg in Tail Flick and Eddy’s hot plate model. The current study also reported that diclofenac has more analgesic activity than tramadol on both 1st and 7th day of treatment.

Total flavonoid content and analgesic activity of ethyl acetate fraction of Indian jujube (Ziziphus mauritiana lamk) leaves

Indian jujube leaves (Ziziphus mauritiana Lamk) have various potential biological activity. Previous studies have proven that ethanol extracted from Indian jujube (Z. mauritiana Lamk) leaves had analgesic activity. This study aimed to determine the total flavonoid content and analgesic activity of the ethyl acetate fraction of Indian jujube (Z. mauritiana Lamk) leaves ethanol extract. Tested fraction was prepared by maceration using ethanol as solvent followed by fractionation using ethyl acetate. Identification of active compounds was performed using color reaction, and determination of total flavonoids by colorimetric method. Ethyl acetate fraction was further tested for its analgesic activity using the writhing method. Swiss-Webster white male mice were divided into 5 treatment groups consisting of negative control contained sodium-CMC, positive control contained sodium diclofenac, while groups 3-5 were given ethyl acetate fraction of Indian jujube (Z. mauritiana Lamk) leaves with doses of 50, 150, and 200 mg/kg BW. All interventions were administered as a single oral dose. 0.7% (w/v) acetic acid was used as a pain inducer. Analgesic activity was measured by calculating the percentage of writhing protection as a measure of the analgesic effect produced by each intervention. The data were analyzed using one-way Anova to compare analgesic activity between treatment groups. Results showed that ethyl acetate fraction of Indian jujube (Z. mauritiana Lamk) leaves at doses of 50, 150, and 200 mg/kg BW gave an effect that was not significantly different from sodium diclofenac as positive control. The ethyl acetate fraction of Indian jujube (Z. mauritiana Lamk) leaves ethanol extract contained flavonoids, saponin, and tannins with total flavonoid content of 22.41 ± 1.16% w/w. It can be concluded that the ethyl acetate fraction of Indian jujube (Z. mauritiana Lamk) leaves have analgesic activity in mice.

Evaluation of Analgesic Activity of Thymoquinone the Major Constituent of Nigella sativa Seeds in Mice

Drugs commonly used in modern medicine for suppression of pain and fever provide only symptomatic relief and long-term use of these drugs is associated with serious adverse effects. Recently, some evidences suggest that Nigella sativa inhibit eicosanoid generation in leukocytes and lipid peroxidation. They are reported to inhibit both cycloxygenase and 5-lipooxygenase pathways of arachidonic acid metabolism. The present study was aimed to evaluate the analgesic activity of pure compound, thymoquinone the major constituent of Nigella sativa seeds in mice. The analgesic activity was determined by hot plate, tail immersion, tail flick method and acetic acid induced writhing test in mice. Thymoquinone (10, 20, 30 mg/kg, body weight) and Aspirin (20mg/kg) made as suspensions prepared in 1% carboxy methyl cellulose and were fed to mice intraperitoneally. In tail flick method thymoquinone exhibited maximum analgesic effect at a dose of 30mg/kg after 120 min as compared to control and standard. Maximum analgesic effect was noted at a dose of 10 mg/kg after 120 min. the poor analgesic effect of thymoquinone at a dose of (20 and 30 mg/kg) as compared to control and standard drug by hot plate method. However with writhing test the thymoquinone showed maximum protection at a dose of 30 mg/kg (98.23%). The thymoquinone have minimum effect showed at dose of 10 mg/kg (69.72%) and 20 mg/kg (42.26%) as compared to standard and control. But in tail immersion method thymoquinone exhibited maximum activity after 120 min at a dose of 20 mg/kg as compared to control and standard drug while at a dose of 30 mg/kg the compound did not showed any further enhancement in analgesic activity. It is concluded from the present study that thymoquinone the major constituent of Nigella sativa possesses potent analgesic activity in mice.&#x0D; Keywords: Thymoquinone, Nigella sativa, Hot plate, Tail immersion, Tail flick method, Acetic acid induced writhing test

Synthesis and Activity Test of 1-Allyl-3-(4-tertiary-Butylbenzoyl) Thioureaas a Candidate of an Analgesic Drug

Background: Urea derivatives showed good analgesic activity compared to diclofenac sodium. The addition of the allyl group to the thiourea and 4-tertiary-butylbenzoyl chlorideis expected to provide a better analgesic effect. Objective: The research aimed to synthesize 1-allyl-3-(4-tertiary-Butylbenzoyl) Thiourea and determine its analgesic activity in mice (Mus musculus). Methods: The synthesis was carried out by a modified Schotten-Baumann reaction, via nucleophilic substitution reaction of allylthiourea on 4-tertiary-butylbenzoyl chloride. A writhing test was performed to observe analgesic activity in the test compound. Confirmation of the structure of pure 1-allyl-3-(4-tertiary-Butylbenzoyl) Thiourea was obtained through UV, IR, 1H-NMR, and 13C-NMR data. Results: The compound showed better pain inhibition activity compared to diclofenac sodium, with ED5019,018 mg/kg BW. Conclusion: The compound 1-allyl-3-(4-tertiary-butylbenzoyl) thiourea showed better analgesic activity than diclofenac sodium.

Solid Dispersion of Tenoxicam – HPMC by Freeze-Drying: Solid State Properties, Dissolution Study, and Analgesic Activity in Mice

AIM: The aim of this study was to prepare solid dispersion of tenoxicam with hydroxypropyl methylcellulose (HPMC) to improve solubility, dissolution rate, and in vivo analgesic activity. METHODS: Solid dispersion of tenoxicam with HPMC was prepared using the freeze-drying technique in three ratios of drug to carrier (1:1, 1:2, and 2:1 w/w). The s olid-state properties of solid dispersion powders were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, and scanning electron microscope (SEM). Solubility and dissolution rate studies were conducted in an aqueous medium. Analgesic activity was evaluated using the writhing method. RESULTS: Analysis of PXRD and DSC results indicated a decreased degree of crystallinity of tenoxicam in solid dispersion powders. Solid dispersion of tenoxicam exhibited a significant improvement in solubility and dissolution rate compared to intact tenoxicam, in line to the increment on the ratio of HPMC. Analgesic activity study revealed that solid dispersion 1:2 was more effective than intact tenoxicam. CONCLUSIONS: This study concludes that the solid dispersion technique is a promising strategy to improve the solubility and dissolution rate of tenoxicam.

An Injectable Hydrogel for Treatment of Chronic Neuropathic Pain

Current treatments for chronic neuropathic pain often fall short. A small-molecular compound ZL006 can suppress N-Methyl-d-aspartate receptor (NMDAR)-mediated neuropathic pain behaviors without blocking essential NMDAR function and brings new hope for neuropathic pain therapy. The persistent nature of neuropathic pain mandates the long-term treatment. However, similar to existing analgesics, ZL006 has only a short duration of action. To unleash the therapeutic potential of ZL006, the stability of ZL006 in aqueous solutions is investigated, and a ZL006-incorporated P407-based thermoresponsive injectable hydrogel is developed. The computational analysis is performed to help achieve the desired ZL006-loaded hydrogel system and elucidate the gelation mechanism. The hydrogel matrix can be loaded with ZL006 in an aqueous phase at room temperature without costly specialized equipment and no organic solvent, where the sol is formed and injectable. On subcutaneous administration and subsequent rapid warming to physiological temperature, the sol is converted to a gel. The thermoresponsive hydrogel at body temperature enables the extended release of encapsulated ZL006, and therefore a single subcutaneous injection of ZL006-hydrogel produces a prolonged and stable analgesic action in mice with spinal nerve ligation. The study provides a practical chronic neuropathic pain therapy and a new perspective on future applications of ZL006.

Oral administration of eucalyptol reduces cell migration and pain-like behavior in zymosan-induced arthritis mice

Rheumatoid arthritis (RA) is an inflammatory disease that utilizes nonbiologic and biologic drugs for appropriate disease management. However, high cost, adverse effects, reduced effectiveness, and risk of infection have stimulated the search for safer and more efficacious therapeutic strategies. In the present study, we aimed to evaluate the anti-inflammatory and analgesic properties of eucalyptol in an experimental model of arthritis. Mice were administered zymosan or saline intra-articularly. One hour before the zymosan administration, the mice were treated with oral eucalyptol (200-400 mg/kg) and vehicle. Cell influx, neutrophils, lymphocytes, and monocytes were measured in joint exudates. Joint pain was assessed using paw-pressure tests. Orally administered eucalyptol (200 and 400 mg/kg) significantly reduced cell influx, as well as neutrophils, lymphocytes, and monocytes, when compared with the control. Eucalyptol at a dose of 400 mg/kg significantly reversed joint pain and demonstrated analgesic activity (60%); however, 200 mg/kg failed to alter joint pain. These results indicate that oral eucalyptol promotes anti-inflammatory and analgesic activity in mice subjected to zymosan-induced arthritis.

Analgesic Effect of Ethanolic Extract of Seeds and Leaves of Coriandrum Sativum on Swiss Albino Mice

INTRODUCTION: Pain has been described by the International Association for the Study of Pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Although NSAIDS and OPIOIDS are available for the treatment, still pain (chronic) is major problem. The present study was designed to study the analgesic effect of ethanolic extract of Coriandrum sativum using hot plate method and acetic acid induced writhing method in experimental animals (Swiss albino mice). MATERIAL AND METHODS:The analgesic effect of leaves and seeds of Coriandrum sativum was assessed using hot plate method and acetic acid induced writhing method in Swiss albino mice. The animals were treated with the ethanolic extract of leaves and seeds of Coriandrum sativum orally at two doses of 100, 500 mg/kg body weight after electric heat and acetic acid induced pain in mice. RESULTS: The study showed that ethanolic extract of leaves and seeds of Coriandrum sativum presented significant (p&lt;0.05) and (p&lt;0.05) analgesic activity in mice simultaneously. The data were analyzed by one-way ANOVA followed by Dunette's multiple comparison test. The results demonstrate that ethanolic extract of leaves and seeds of Coriandrum sativum has got analgesic potential. CONCLUSION: The results demonstrate that ethanolic extract of leaves and seeds of Coriandrum sativum has got significant analgesic effect.

Analgesic and anti-inflammatory effects and safety profile of Cucurbita maxima and Cucumis sativus seeds.

The premise of the pharmacology of natural product is to explore benefits of natural resources for the mankind. Medicines extracted from natural resources are considered as primary source for drug discovery. Thus, the current study was designed to evaluate the safety profile and explore the analgesic and anti-inflammatory activity of ethanol extract of Cucurbita maxima (C. maxima) and Cucumis sativus (C. sativus) seeds. These seeds are edible, good in taste and have been used for several therapeutic purposes. Acute toxicity of the seeds was evaluated by Lorke’s method while Eddy’s hot plate and tail immersion methods were used to assess analgesic activity in mice. Anti-inflammatory activity was evaluated by rat hind paw edema method. The seed extracts of C. maxima and C. sativus were found to be safe and showed significant analgesic and anti-inflammatory activity in comparison with the control group. The therapeutic effects of these extracts were almost comparable to aspirin and brufen. Therefore, the seeds can be used as effective analgesic and anti-inflammatory agents.

Wide-Range Measurement of Thermal Preference-A Novel Method for Detecting Analgesics Reducing Thermally-Evoked Pain in Mice.

Background: Wide use of oxaliplatin as an antitumor drug is limited by severe neuropathy with pharmacoresistant cold hypersensitivity as the main symptom. Novel analgesics to attenuate cold hyperalgesia and new methods to detect drug candidates are needed. Methods: We developed a method to study thermal preference of oxaliplatin-treated mice and assessed analgesic activity of intraperitoneal duloxetine and pregabalin used at 30 mg/kg. A prototype analgesiameter and a broad range of temperatures (0–45 °C) were used. Advanced methods of image analysis (deep learning and machine learning) enabled us to determine the effectiveness of analgesics. The loss or reversal of thermal preference of oxaliplatin-treated mice was a measure of analgesia. Results: Duloxetine selectively attenuated cold-induced pain at temperatures between 0 and 10 °C. Pregabalin-treated mice showed preference towards a colder plate of the two used at temperatures between 0 and 45 °C. Conclusion: Unlike duloxetine, pregabalin was not selective for temperatures below thermal preferendum. It influenced pain sensation at a much wider range of temperatures applied. Therefore, for the attenuation of cold hypersensitivity duloxetine seems to be a better than pregabalin therapeutic option. We propose wide-range measurements of thermal preference as a novel method for the assessment of analgesic activity in mice.

Methanol, ethyl acetate and n-hexane extracts of Tragia involucrata L. leaves exhibit anxiolytic, sedative and analgesic activity in Swiss albino mice

IntroductionTragia involucrata L. have been utilized as traditional medicine in Indian subcontinent for the treatment of numerous illnesses such as inflammation, pain and skin infection. In this current study we sought to assess the anxiolytic, sedative and analgesic activity of Tragia involucrata L. leaves extract. Materials and methodsWe first performed a phytochemical screening test of the leaves extracts following standard phytochemical screening protocols. We next examined the anxiolytic and sedative activity of crude methanol (TIME), ethyl acetate (TIEAE) and n-Hexane (TIHE) extract of Tragia involucrata L. leaves using mouse behavioral models such as elevated plus-maze test and pentobarbital-induced sleeping time test, respectively. Likewise, we evaluated the analgesic activity using acetic acid induced writhing test and formalin induced paw licking test. Additionally, we performed a quantitative analysis of heavy metals content of Tragia involucrata L. leaves by overnight digestion in concentrated nitric acid (HNO3). ResultsPhytochemical screening demonstrated that TIME, TIEAE and TIHE contain flavonoids, alkaloids, tannins, phenols, terpenoids and sterols. Administration of these extracts resulted in higher number of open arm entry, lower number of close arm entry and higher time spent in open arm compared to control treatment (p < 0.05). Moreover, these treatments decreased the onset of sleep time and increased the duration of sleep compared to control treated mice (all p < 0.05). Likewise, extracts treated mice exhibited decreased number of writhing as well as lower acute phase and late phase duration compared to control treatment (all p < 0.05). The average level of As and Fe in Tragia involucrata L. leaves was 5.16 ± 0.012 ppm and 2.76 ± 0.015 ppm, respectively. ConclusionResults from this study support that Tragia involucrata L. leaves extracts exhibit an anxiolytic, sedative and analgesic activity in mice.

Analgesic Effects of Topical Amitriptyline in Patients With Chemotherapy-Induced Peripheral Neuropathy: Mechanistic Insights From Studies in Mice

Oral amitriptyline hydrochloride (amitriptyline) is ineffective against some forms of chronic pain and is often associated with dose-limiting adverse events. We evaluated the potential effectiveness of high-dose topical amitriptyline in a preliminary case series of chemotherapy-induced peripheral neuropathy patients and investigated whether local or systemic adverse events associated with the use of amitriptyline were present in these patients. We also investigated the mechanism of action of topically administered amitriptyline in mice. Our case series suggested that topical 10% amitriptyline treatment was associated with pain relief in chemotherapy-induced peripheral neuropathy patients, without the side effects associated with systemic absorption. Topical amitriptyline significantly increased mechanical withdrawal thresholds when applied to the hind paw of mice, and inhibited the firing responses of C-, Aβ- and Aδ-type peripheral nerve fibers in ex vivo skin-saphenous nerve preparations. Whole-cell patch-clamp recordings on cultured sensory neurons revealed that amitriptyline was a potent inhibitor of the main voltage-gated sodium channels (Nav1.7, Nav1.8, and Nav1.9) found in nociceptors. Calcium imaging showed that amitriptyline activated the transient receptor potential cation channel, TRPA1. Our case series indicated that high-dose 10% topical amitriptyline could alleviate neuropathic pain without adverse local or systemic effects. This analgesic action appeared to be mediated through local inhibition of voltage-gated sodium channels. PerspectiveOur preliminary case series suggested that topical amitriptyline could provide effective pain relief for chemotherapy-induced peripheral neuropathy patients without any systemic or local adverse events. Investigation of the mechanism of this analgesic action in mice revealed that this activity was mediated through local inhibition of nociceptor Nav channels.

Evaluation of the analgesic activity of ethanolic extract of Populus deltoides leaves in mice

The ethanolic leaves extract of Populus deltoides was tested for the presence of various phytoconstituents and designed to evaluate the analgesic activity in mice. The peripheral analgesic activity of ethanolic leaves extract of P.deltoides (250 and 500 mg/kg) was studied by using acetic acid stimulated writhing test and central analgesic activity of P.deltoides was studied by using hotplate process. The ethanolic leaves extract of P.deltoides professed the existence of a variety of chemical constituents like alkaloids, saponins, flavonoids, terpenes and steroids. Leaves extract of P.deltoides appreciably decreased the writhing actions in acetic acid-induced writhing test in mice and amplified the respond time in hotplate test. These results suggest that the extract may have NSAIDs like activity through the peripheral mechanism and central analgesic activities via opioid receptors. From our study, we endowed that leaves extract of P.deltoides has feasible to analgesic activity. This study reveals that it can be used in the management of pain and provide a scientific basis for its traditional use.

Anti-inflammatory and analgesic activities of indigo through regulating the IKKβ/IκB/NF-κB pathway in mice.

This study investigated the anti-inflammatory and analgesic activities of indigo in mice and explored the possible related mechanisms. Xylene-induced ear edema, carrageenan-induced paw edema, and acetic acid-induced vascular permeability tests were used in investigating the anti-inflammatory activities. The anti-nociceptive effects of indigo were assessed through acetic acid-induced writhing, hot plate test, and formalin test, and spontaneous locomotor activity and motor performance were evaluated. The mechanisms of activities of indigo were explored by evaluating the expression levels of IκB kinase (IKK)β, p-IKKβ, inhibitor κB (IκB)α, p-IκBα, p65 nuclear factor (NF)-kB, p-p65 NF-κB, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) through western blotting and the expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) through enzyme-linked immunosorbent assay. The results showed that indigo significantly reduced xylene-induced ear edema, carrageenan-induced paw edema, and acetic acid-induced vascular permeation. In addition, indigo significantly inhibited nociception induced by acetic acid and formalin. However, the level of nociception was not decreased by indigo in the hot plate test, and indigo did not affect spontaneous locomotor activity and motor performance. The expression levels of p-IKKβ, p-IκBα, p65 NF-kB, p-p65 NF-κB, COX-2, iNOS, TNF-α, IL-1β, IL-6, and PGE2 decreased, whereas the expression level of IκBα increased obviously after indigo treatment. In conclusion, indigo exerts significant anti-inflammatory and analgesic activities in mice by inhibiting IKKβ phosphorylation and reducing the production of important pain mediators, such as PGE2 and COX-2, via the IKKβ/IκB/NF-κB pathway.