Tail Immersion Test Research Articles

Slick Potassium Channels Control Pain and Itch in Distinct Populations of Sensory and Spinal Neurons in Mice

Slick, a sodium-activated potassium channel, has been recently identified in somatosensory pathways, but its functional role is poorly understood. The authors of this study hypothesized that Slick is involved in processing sensations of pain and itch. Immunostaining, in situ hybridization, Western blot, and real-time quantitative reverse transcription polymerase chain reaction were used to investigate the expression of Slick in dorsal root ganglia and the spinal cord. Mice lacking Slick globally (Slick-/-) or conditionally in neurons of the spinal dorsal horn (Lbx1-Slick-/-) were assessed in behavioral models. The authors found Slick to be enriched in nociceptive Aδ-fibers and in populations of interneurons in the spinal dorsal horn. Slick-/- mice, but not Lbx1-Slick-/- mice, showed enhanced responses to noxious heat in the hot plate and tail-immersion tests. Both Slick-/- and Lbx1-Slick-/- mice demonstrated prolonged paw licking after capsaicin injection (mean ± SD, 45.6 ± 30.1 s [95% CI, 19.8 to 71.4]; and 13.1 ± 16.1 s [95% CI, 1.8 to 28.0]; P = 0.006 [Slick-/- {n = 8} and wild-type {n = 7}, respectively]), which was paralleled by increased phosphorylation of the neuronal activity marker extracellular signal-regulated kinase in the spinal cord. In the spinal dorsal horn, Slick is colocalized with somatostatin receptor 2 (SSTR2), and intrathecal preadministration of the SSTR2 antagonist CYN-154806 prevented increased capsaicin-induced licking in Slick-/- and Lbx1-Slick-/- mice. Moreover, scratching after intrathecal delivery of the somatostatin analog octreotide was considerably reduced in Slick-/- and Lbx1-Slick-/- mice (Slick-/- [n = 8]: 6.1 ± 6.7 bouts [95% CI, 0.6 to 11.7]; wild-type [n =8]: 47.4 ± 51.1 bouts [95% CI, 4.8 to 90.2]; P = 0.039). Slick expressed in a subset of sensory neurons modulates heat-induced pain, while Slick expressed in spinal cord interneurons inhibits capsaicin-induced pain but facilitates somatostatin-induced itch.

Oral administration of essential oil from Psidium glaziovianum Kiaersk leaves alleviates pain and inflammation in mice.

Plants of the genus Psidium have been employed in "in natura" consumption and agroindustry, and owing to the diversity of phytochemicals, the development of new pharmaceutical forms has received remarkable research interest. In this study, the essential oil obtained from Psidium glaziovianum (PgEO) leaves were evaluated antinociceptive and anti-inflammatory activities were evaluated in mouse models. Initially, PgEO was characterized by gas chromatography-mass spectrometry and gas chromatography with flame ionization detection, and the profile was dominated by sesquiterpene compounds. In the evaluation of acute antinociceptive activity (abdominal contortions induced by acetic acid, formalin, tail immersion, and hot plate tests), PgEO promoted a reduction in nociception in the chemical and thermal models. Additionally, the potential underlying mechanism was investigated using pain pathway blockers, and the results revealed a combined action of opioidergic and muscarinic pathways. The anti-inflammatory potential was confirmed by anti-edematogenic action, reduced cell migration, pro-inflammatory cytokine production, and granuloma formation in chronic processes. This study provides evidence that PgEO can be effective for the treatment of pain and acute and chronic inflammation.

Caralluma tuberculata exhibits analgesic and anti-arthritic potential by downregulating pro-inflammatory cytokines and attenuating oxidative stress.

Caralluma tuberculata N.E. Brown (Common name: Chongan), belonging to the family Asclepiadaceae is distributed widely in hilly areas of Dir, Swat, Kohat and in plain lands of Punjab, Pakistan. The plant has been used as a source of vegetable as well as home remedy for headache, muscle spasms and rheumatism. The present study was proposed to investigate the analgesic, anti-inflammatory and anti-arthritic potential of the aqueous methanolic extract of C. tuberculata (ICE). The dried shoots of plant were used to prepare aqueous methanolic extract (30:70) by 3days thrice maceration and filtration followed by evaporation under reduced pressure. ICE was screened for the presence of phytochemicals using preliminary phytochemical analysis and HPLC. The antioxidant potential was evaluated through DPPH assay. Analgesic potential of ICE was studied using hot plate and tail immersion methods, and anti-inflammatory activity was performed using turpentine oil and carrageenan-induced inflammation models, in wistar albino rats. Formaldehyde-induced and Complete Freund's Adjuvant-induced arthritis models were used for the assessment of anti-arthritic activity of ICE and its effects on serum levels of PGE-2 as well as gene expression levels of pro-inflammatory cytokines were studied. ICE displayed a dose-dependent (300-1000mg/Kg p.o.) analgesic effect in hot plate (maximum retention time of 10.87 and 13s) and tail immersion (response time of 11 and 13.64s) tests at the doses of 500 and 1000mg/Kg, respectively. The extract exhibited a significant decrease in paw inflammation of rats at the doses of 500 and 1000mg/Kg as compared to the disease control group. ICE also exhibited a remarkable decline in arthritic score and a dose-dependent drop in serum levels of prostaglandin E2. There was a significant suppression in the expression of TNF-α, IL-1β, IL-6, NF-κB and cyclooxygenase enzyme in treatment groups. This study concludes that Caralluma tuberculata exhibits strong analgesic, anti-inflammatory, antioxidant and anti-arthritic activities thus upholding the vernacular use of the plant for pain and rheumatism.

Central metabolism as a potential origin of sex differences in morphine antinociception but not induction of antinociceptive tolerance in mice.

In rodents, morphine antinociception is influenced by sex. However, conflicting results have been reported regarding the interaction between sex and morphine antinociceptive tolerance. Morphine is metabolised in the liver and brain into morphine-3-glucuronide (M3G). Sex differences in morphine metabolism and differential metabolic adaptations during tolerance development might contribute to behavioural discrepancies. This article investigates the differences in peripheral and central morphine metabolism after acute and chronic morphine treatment in male and female mice. Sex differences in morphine antinociception and tolerance were assessed using the tail-immersion test. After acute and chronic morphine treatment, morphine and M3G metabolic kinetics in the blood were evaluated using LC-MS/MS. They were also quantified in several CNS regions. Finally, the blood-brain barrier (BBB) permeability of M3G was assessed in male and female mice. This study demonstrated that female mice showed weaker morphine antinociception and faster induction of tolerance than males. Additionally, female mice showed higher levels of M3G in the blood and in several pain-related CNS regions than male mice, whereas lower levels of morphine were observed in these regions. M3G brain/blood ratios after injection of M3G indicated no sex differences in M3G BBB permeability, and these ratios were lower than those obtained after injection of morphine. These differences are attributable mainly to morphine central metabolism, which differed between males and females in pain-related CNS regions, consistent with weaker morphine antinociceptive effects in females. However, the role of morphine metabolism in antinociceptive tolerance seemed limited. This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc.

Antinociception Induced by Moringa Stenopetela (Baker f.) Cufod. Leaves Extract and Possible Mechanisms of Action

Moringa stenopetala (Baker f.) Cufod., is an endemic species growing in the south of Ethiopia. M. stenopetala is often consumed as food and used in traditional medicine and it has also been traditionally used for relieving of pain in Ethiopia. This study aimed to investigate the antinociceptive effect and mechanisms of action of M. stenopetala leaves methanol extract in mice. The per-oral doses of 50, 100, and 200 mg/kg of M. stenopetala extract were tested for antinociceptive action by using hot-plate, tail-immersion, and writhing tests. The possible mechanisms of in the antinociceptive action were investigated by pre-treatment with 5 mg/kg naloxone (non-selective opioid antagonist), 1 mg/kg ketanserin (5-HT2A/2C receptor antagonist), and 1 mg/kg yohimbine (α2 adrenoceptor antagonist). The methanol extract of M. stenopetala showed antinociceptive effect in all tests. The significant involvement of 5-HT2A/2C receptors and α2 adrenoceptors in antinociception induced by M. stenopetala extract in the hot-plate and tail-immersion tests, as well as significant contribution of opioid receptors and α2 adrenoceptors in writhing test, were identified. In conclusion, these findings demonstrate that the methanol extract of M. stenopetala has potential in pain management. Thisstudywillcontributetonewtherapeuticapproachesandprovideguidancefornewdrug development studies.

Effects of Azadirachta indica on neuropathic pain induced by chronic constriction injury to sciatic nerve of Wistar rat.

The research was designed to assess the consequences of Azadirachta indica aqueous leaf extract (AILE) on neuropathic pain in Wister rats and the role of the ATP-dependent potassium channel (KATP) as an underlying mechanism. This experimental layout was conducted on Wistar rats (n = 120) having 150 to 200 gm of body weight. On the foundation of the experimental design, rats were divided into group I (normal saline, 5 ml/kg/body weight) and group II (sham surgery and treatment with NS), group III [chronic constriction injury (CCI) in the sciatic nerve; and treated with NS], group IV (CCI and treated with AILE 400 mg/kg body weight), Group V (CCI, pretreated with Glibenclamide 15 mg/kg followed by treated with AILE 400 mg/kg). All the treatments were given once daily for a consecutive 21 days via the oral route, except Glibenclamide. Glibenclamide was given once through the intraperitoneal route on the day of the experiment. Based on the neuropathic pain evaluation test, all groups were again sub-divided into subgroup "a" (walking tract analysis), "b" (cold tail immersion test), "c" (Von Frey test), and "d" (hot plate test). AILE showed a significantly higher sciatic functional index (p < 0.05) in walking track analysis, tail flick latency (p ≤ 0.05) in the cold tail immersion test, and paw withdrawal threshold (p ≤ 0.05) in the Von Frey test compared to CCI control. In addition, a nonsignificant difference in all these above-mentioned variables between the rats with CCI plus AILE and the CCI plus AILE plus glibenclamide group indicated that the KATP channel was not involved in the beneficial analgesic effects of AILE. The outcome of the present study indicates that AILE prevented worsening of neuropathic pain after chronic constriction injury in the sciatic nerve of Wistar rats in which the KATP channel was not involved.

An in vivo evaluation of anti-inflammatory, analgesic and anti-pyretic activities of newly synthesized 1, 2, 4 Triazole derivatives

BackgroundIn recent years, 1, 2, 4-triazole and its derivatives have been reported to be pharmacologically significant scaffolds. They possess analgesic, anti-tubercular, anti-inflammatory, anti-convulsant, anti-oxidant, anti-fungal, anti-cancer, anxiolytic and anti-depressant activity. This study was designed and conducted to evaluate the potential anti-inflammatory, analgesic and antipyretic activities of Triazole derivatives.MethodsSwiss albino (male and female) mice weighing 20-30 g (10-24 weeks female), (5-14 weeks male) and Wister Kyoto rats (male and female) weighing 200-300 g (8-10 weeks old) were used for the present study. Anti-inflammatory activity was checked using Lambda carrageenan (λ) and egg albumin-induced paw edema models. Analgesic via Writhing Reflex induced by acetic acid and formalin, furthermore anti-pyretic activity was assessed by yeast induced pyrexia.ResultsBoth of the test compounds exhibited encouraging anti-inflammatory analgesic and antipyretic results when compared with standard drug ibuprofen. The maximum inhibition of edema for the compound (S)-1-(4-Amino-5-mercapto-4H-1,2,4-triazole-3-yl) ethanol [3] was found to be (91)% as compared to reference drug ibuprofen (82)%, while (S)-1-(6-Phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)ethanol [5e] showed equipotent results to ibuprofen (81)%. The derivatives were also screened for their anti-nociceptive activity by Acetic acid writhing and tail immersion test. Compound 3 showed a significant reduction in wriths (83)% as compared to standard drug ibuprofen 71.5% and [5] showed comparable results to ibuprofen by exhibiting 70% reduction in writh at the same dose as that of standard drug, moreover, there were no signs of toxicity being observed after administration of high doses of test compounds to mice.ConclusionsIt is evident from the results that compounds 3(compound A) and 5(compound B) are a potential candidate for anti-inflammatory, analgesic and anti-pyretic and the scaffold could be used for further structural modifications. Further studies would help to evaluate their molecular mechanism of action regarding these beneficial activities.

Analgesic, Anti-inflammatory and Antipyretic Activity of Rotula aquatica Lour Leave

The present study was aimed to evaluate analgesic, anti-inflammatory and anti pyretic activity of methanolic extract and aqueous extract of leave of Rotula aquatica L. in mice and rats. The methanolic extract of R. aquatica L. leave at a dose of 200mg/kg body weight has shown significant analgesic, antipyretic and anti-inflammatory activity as compared to aqueous extract. The result of hot plate method indicated that the total methanolic extract showed significant increase (P&lt;0.01) in reaction time at a 3,4and 6 hours comparable to the reference drug Pentazocin but lesser (P&lt;0.05) after 2hr. The tail immersion and hot plate tests revealed that plant has high analgesic activity. Both tests showed highest degree of analgesia in methanolic extract compared to aqueous extract. The total methanolic extract of R.aquatica L. leave at the a dose of 200mg/kg body weight has shown significant (p&lt;0.01) antipyretic activity as compared to aqueous extract, methanolic extract also found to have significant result in Carrageenin-induced paw oedema; suspect edmodeo faction may be due to possible inhibition of lipooxygenase pathway.

Securidaca inappendiculata Polyphenol Rich Extract Counteracts Cognitive Deficits, Neuropathy, Neuroinflammation and Oxidative Stress in Diabetic Encephalopathic Rats via p38 MAPK/Nrf2/HO-1 Pathways.

Diabetic encephalopathy is one of the serious emerging complication of diabetes. Securidaca inappendiculata is an important medicinal plant with excellent antioxidant and anti-inflammatory properties. This study investigated the neuroprotective effects of S. inappendiculata polyphenol rich extract (SiPE) against diabetic encephalopathy in rats and elucidated the potential mechanisms of action. Type 2 diabetes mellitus (T2DM) was induced using high fructose solution/intraperitoneal injection of streptozotocin and the diabetic rats were treated with SiPE (50, 100 and 200 mg/kg) for 8 weeks. Learning and memory functions were assessed using the Morris water and Y maze tests, depressive behaviour was evaluated using forced swimming and open field tests, while neuropathic pain assessment was assessed using hot plate, tail immersion and formalin tests. After the experiments, acetylcholinesterase (AChE), oxidative stress biomarkers and proinflammatory cytokines, caspase-3 and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) were determined by ELISA kits. In addition, the expression levels of p38, phospho-p38 (p-p38), nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were determined by western blot analyses. The results indicated that SiPE administration significantly lowered blood glucose level, attenuated body weight loss, thermal/chemical hyperalgesia, improved behavioural deficit in the Morris water maze, Y maze test and reduced depressive-like behaviours. Furthermore, SiPE reduced AChE, caspase-3, NF-κB, malonaldehyde malondialdehyde levels and simultaneously increased antioxidant enzymes activity in the brain tissues of diabetic rats. SiPE administration also significantly suppressed p38 MAPK pathway and upregulated the Nrf2 pathway. The findings suggested that SiPE exerted antidiabetic encephalopathy effects via modulation of oxidative stress and inflammation.

Neuroprotective effect of Bauhinia variegata Linn. leaf extracts in streptozotocin induced diabetes in Sprague Dawley rats.

Bauhinia variegata, a ayurvedic medicinal plant reported for its valuable effects in various diseases. It has shown significant effects in type 1 and type 2 diabetes. The present work was designed to study effects of aqueous and alcoholic extract (AE and AlcE) of Bauhinia variegata Linn. leaves in diabetic neuropathy. Male Sprague Dawley rats become diabetic using intraperitoneal injection of streptozotocin (STZ) at 55mg/kg dose. After 6weeks, animals were divided and were treated with AE and AlcE at a dose of 250, 500, and 1000mg/kg (p. o.) for the next four weeks. Various parameters such as glucose, thermal hyperagesia, mechanical allodynia, MNCV and oxidative stess were assessed at the end of the study. Diabetic animals showed a significant reduction in response time in tail immersion and hot plate test as compared to animals in normal control group. AE and AlcE at 250, 500, and 1000mg/kg dose significantly increased response time in the tail immersion test. Whereas, AE and AlcE at doses 500 and 1000mg/kg showed significant improvement and in response time in the hot plate test.AlcE at 250, 500 and 1000mg/kg dose increased the nociceptive threshold significantly. AE at doses 500 and 1000mg/kg showed significant improvement in the nociceptive threshold. The decrease in motor nerve conduction velocity was observed in diabetic control animals, which was significantly improved after AlcE treatment as compared to AE treatment. Treatment with AE and AlcE decreased the lipid peroxidation and increased the antioxidant enzyme activity significantly in the sciatic nerve. The results showed that Bauhinia variegata extracts may be considered as a effective option for management of diabetic neuropathy.

Analgesic properties of dealcoholized extract of Acorus Calamus Leaves

Opioid and non-narcotic analgesics, non-steroidal anti-inflammatory agents, anesthetics, antidepressants, myorelaxants, combined agents and phytopreparations are widely used for the treatment of pain syndrome. One of the promising phytogenic objects with potential analgesic properties is the Acorus calamus (Sweet Flag).&#x0D; The aim: the purpose of the study is to determine the analgesic effect of the dealcoholized extract of Acorus calamus leaves (DEAL) on a model of pain in the "Hot plate" test and in the test of tail heat immersion.&#x0D; Materials and methods. During the experimental study, the pharmacological methods have been used. The analgesic properties of DEAL were studied in mice on the "Hot plate" model using the Hot / Cold Plate (Bioseb, France) and in the test of the heat immersion in rats.&#x0D; The results. On the models of pain in the "Hot plate" and tail heat immersion tests, the analgesic effect of the dealcoholized extract of Acorus calamus leaves (DEAL) is determined. On the "Hot plate" model, the use of DEAL probably increased the duration of the latency period. According to the analgesic effect of DEAL and metamizol sodium were comparable to each other continues to 1 and 1.5 hours of experiment, but starting with 2 hours of experiment the analgesic action of metamizol sodium statistically exceeded the analgesic effect of DEAL.&#x0D; In the test of heat immersion tail in rats, DEAL increased the latency period of shocking of the rats’ tail compared to the starting background by 43.13 % as well as metamizol sodium by 66.6 %. The studies have shown the presence of moderate analgesic effects of DEAL in the investigated dose.&#x0D; Conclusions. The analgesic effect of a dealcoholized extract of Acorus calamus leaves (DEAL) on a model of pain in the "Hot plate" and heat tail immersion tests has been carried out. Under the "Hot plate" test in mice, DEAL produces a distinct analgesic effect, however, slightly inferior to the severity of metamizol sodium. Presence of moderate analgesic properties of DEAL has been verified in comparison with the metamizel sodium in thetail heat immersion test in rats. The obtained results indicate the influence of DEAL on the central mechanisms of pain formation

Diurnal efficacy of alpha-lipoic acid/nifedipine/glimepiride combination mitigates diabetic neuropathies in rats

Time-dependent effects of alpha-lipoic acid/nifedipine/glimepiride combination on diabetic neuropathies were investigated in rats. 7 groups (n=9) of rats were used. First and second groups were apparently normal and diabetic rats respectively, and were administered 1mL/kg distilled water. The rest of the groups were diabetic and administered 10mg/kg glimepiride at night-time (8:00 pm). Groups 4-7 were administered additional 20mg/kg nifedipine at morning-time (8:00 am), while groups 5-7 were also administered 100mg/kg alpha-lipoic acid (ALA) in the morning, afternoon and night-time respectively (8:00 am, 2:00 pm and 8:00 pm). During the 28 days of oral treatment, paw pressure, tail immersion and motor coordination tests were conducted. The rats were euthanized on the 29th day after a charcoal meal. The small intestines were excised to determine intestinal transit while the brain was collected, homogenised and used to determine levels of oxidative stress. Data show that treatment with ALA at 8:00 am or 2:00 pm significantly (P≤0.01) produced a delay in the onset and improved prognosis of neuropathies. Treatment with ALA at 8:00 pm prevented manifestation of neuropathies throughout the study with positive antioxidant effects. Time-dependent ALA treatment in combination with nifedipine and glimepiride should be studied in humans with an approximately similar circadian timing. This may provide additional clinical therapeutic options for diabetic neuropathies.

Central possible antinociceptive mechanism of naringin

Background and Aims: The object of this study was the investigation of the central antinociceptive effects of naringin as well as the association of stimulation of opioidergic, serotonergic, adrenergic, and cholinergic (muscarinic and nicotinic) receptors to the central analgesia of mice due to naringin. Methods: Several intraperitoneal doses (20, 40, and 80 mg/kg) were injected into mice models and analyzed via hot-plate (integrated supraspinal response) and tail-immersion (spinal reflex) for the possible antinociceptive effects of naringin. Moreover, the involved action mechanism was investigated using 80 mg/kg naringin (i.p.) administered to the mice which were previously pre-treated with opioid antagonist naloxone (5 mg/kg, i.p.), serotonin 5-HT2A/2C receptor antagonist ketanserin (1 mg/kg, i.p.), α2-adrenoceptor antagonist yohimbine (1 mg/kg, i.p.) and muscarinic antagonist atropine (5 mg/kg, i.p.), as well as nicotinic antagonist mecamylamine (1 mg/kg, i.p.). Results: It can be claimed that a dose-dependant antinociceptive effect of naringin was noticed for 40 and 80 mg/kg doses in tail-immersion and hot-plate tests, respectively. Furthermore, the improvement of inactivity of naringin-induced response to thermal stimuli was counteracted by mecamylamine and naloxone when tested with the tail-immersion test, and hot-plate analyses. Conclusion: From the data, it was confirmed that naringin presents central antinociceptive effects which may be coordinated by supraspinal/spinal mediated opioidergic and nicotinic (cholinergic) inflection. Nevertheless, it is unclear how naringin organizes the interactions of the aforementioned modulatory systems. To conclude, naringin could be a possible candidate for pain relief management.

Antinociceptive, Anti-Hyperalgesia and Antiallodynic Activities of Polyphenol Rich Extract from Shorea roxburghii against Cyclophosphamide Induced Peripheral Neuropathy.

Cyclophosphamide (CYP) is a widely used antineoplastic and immunosuppressive drug, however, despite its efficacy, it has shown extensive multiple organ toxicities, including peripheral neuropathy which significantly affects the quality of life of cancer patients. This study elucidated the protective properties of Shorea roxburghii polyphenol extract (SLPE) in CYP-induced peripheral neuropathy. Rats were treated with SLPE (100 and 400 mg/kg) for five weeks plus CYP once a week from the second week of SLPE treatment. Using UHPLC-QTOF-MS, 54 polyphenolic compounds were identified in SLPE extract. After the treatment period the antinociceptive, anti-hyperalgesia and antiallodynic effects was evaluated using formalin paw edema, acetic acid abdominal writhing, hot plate, tail immersion and von Frey filament tests. While the locomotive and motor coordination effects were evaluated by open field and rotarod tests. The administration of CYP led to significant increases in mechanical and thermal hyperalgesia, in addition to hyper-nociceptive responses in the formalin and acetic acid writhing tests. CYP also significantly reduced locomotive activity and motor coordination. SLPE significantly protected against CYP-induced mechanical and thermal hyperalgesia. Furthermore, SLPE displayed robust antinociceptive effect by counteracting formalin and acetic acid induced hyper-nociception. In addition, SLPE increased the locomotive activity as well as the grip and motor coordination of the CYP treated rats. In conclusion, these results revealed the protective effects of SLPE against CYP-induced peripheral neuropathy and could be an effective therapeutic remedy for chemotherapy induced peripheral neuropathy.

Acute Toxicity Study and Anti-Nociceptive Activity of Ethanol Extract of Aesculus Indica Seeds on Experimental Animal Models

Aesculus indica, widely known as the horse chestnut tree, has long been used as antiangiogenic, antibacterial, antidiabetic, antiviral and antifungal. Ttraditionally it has been used as medicine for the treatment of skin diseases, rheumatism and different pain conditions. The current study was undertaken to investigate possible effects of ethanol extract of seeds of plant in experimentally produced pain in animals because there were no scientific publications on the use of Aesculus indica seeds for anti-nociceptive activity. Preliminary phytochemical screening revealed the presence of flavonoids, tannins, carbohydrates, Saponins, and phenolic substances in the extract. The OECD guideline 423 was followed for acute toxicity testing.At a dose of 2000 mg/kg, the extract was confirmed to be safe. The anti-nociceptive effect of three distinct dose levels of extract (100, 200, and 300 mg/kg) was tested in Swiss albino mice using a hot plate, tail immersion test, and acetic acid induced writhing. Extract had strong anti-nociceptive efficacy (P &lt; 0.001) in a hot plate test. The extract significantly increased the tail withdrawal reaction in the tail immersion test (P &lt; 0.001).The extract considerably reduced the number of writhes in the acetic acid writhing test (P &lt; 0.001). The findings indicate that the extract has substantial anti-nociceptive effect.&#x0D;

Pharmacological Evaluation of Antipyretic, Analgesic and Anti-inflammatory Activities of Ethanolic Extract of Cassia fistula

Background: The antipyretic, analgesic and anti-inflammatory activities of two concentrations (100 and 200 mg/kg) of ethanolic extract of leaf, bark, flower and fruit pulp of C. fistula were determined in male wistar albino rats. Methods: Antipyretic activity was assessed by E. coli endotoxin induced pyrexia. Analgesic activity was assessed by hot plate, tail immersion and acetic acid induced writhing test. Anti-inflammatory activity was evaluated by carrageenan-induced rat paw edema assay. Result: Significant (p less than 0.05) antipyretic activity was exhibited from 2h onwards by bark extract @ 200 mg/kg and from 3h onwards by bark extract @100 mg/kg and leaves extract @ 200mg/kg as compared to control group. Significant (p less than 0.05) analgesic activity was shown by extract of bark @ 200 mg/kg as it is evident by increase in reflex time in hot plate (90,120,180 min), tail immersion test (120,180 min) and inhibition of writhing (32.12%). Significant (p less than 0.05) anti-inflammatory activity was exhibited from 3h post administration by bark @ 200 and leaves @ 100 and 200 mg/kg.

Analgesic Effect of Ziziphus abyssinica Involves Inhibition of Inflammatory Mediators and Modulation of KATP Channels, Opioidergic and Nitrergic Pathways.

The diversity offered by natural products has timelessly positioned them as a good source for novel therapeutics for the management of diverse medical conditions, including pain. This study evaluated hydro-ethanolic root bark extract of Ziziphus abyssinica (ZAE) as well as β-amyrin and polpunonic acid isolated from the plant for analgesic property. The study also investigated the mechanism responsible for this action in the extract. The antinociceptive potential of ZAE (30, 100, and 300 mg/kg, p. o.) was assessed using the tail-immersion test (TIT), acetic acid-induced writhing test (AAT), and formalin test (FT). The extract’s effect on acute and chronic musculoskeletal pain was also assessed by administering carrageenan unilaterally into the rat gastrocnemius muscles and measuring pain at 12 h and 10 days for acute and chronic pain respectively. The involvement of pro-inflammatory mediators (prostaglandin E2, bradykinin, TNF-α, and IL-1β) was assessed. The possible pathways mediating the observed analgesic effect of ZAE were further assessed using the antagonists: naloxone, glibenclamide, NG-L-nitro-arginine methyl ester (L-NAME), atropine, nifedipine, and yohimbine in the FT. Also the analgesic effect of two triterpenoid compounds, β-amyrin and polpunonic acid, previously isolated from the plant was assessed using the TIT. The anti-nociceptive activity of ZAE was demonstrated in the TIT by the significant (p < 0.05) increase in tail withdrawal threshold in ZAE-treated mice. ZAE also markedly reduced writhing and paw licking responses in both AAT and FT and significantly (p < 0.05) attenuated both acute and chronic musculoskeletal pain. ZAE also significantly reversed hyperalgesia induced by intraplantar injection of PGE2, bradykinin, TNF-α, and IL-1β. Furthermore, data revealed the involvement of opioidergic, ATP-sensitive K+ channels and NO-cGMP pathways in the analgesic effect of ZAE. Both β-amyrin and polpunonic acid exhibited analgesic activity in the tail suspension test. Our study demonstrates ZAE as an important source of new therapeutic agents for pain management.

Echinodorus macrophyllus fraction with a high level of flavonoid inhibits peripheral and central mechanisms of nociception

Background and aim: Echinodorus macrophyllus (Kunth.) Micheli is popularly used for acute and chronic inflammatory conditions. The anti-inflammatory activity was previously demonstrated for its flavonoid-enriched fractions. The aim of this work assessed the antinociceptive properties of both aqueous extract and its fractions. Experimental procedure: The antinociceptive activity was determined by acetic acid-induced writhing, formalin test, tail immersion test, hot-plate test, xylene-induced ear edema methods, and the evaluation of its mechanism was performed in the writhing model. The aqueous extract of Echinodorus macrophyllus (AEEm) was fractionated, yielding Fr20, and Fr40. Fr40 composition was determined by HPLC-DAD-ESI-MS. Results and conclusion: Fr20 (all doses) and Fr40 (100 mg/kg) reduced the nociception in the tail-flick model. Both fractions increased the percentage of maximum possible effect with 25 mg/kg, in the hot-plate assay, at 60 min, while AEEm reduced pain only with 50 and 100 mg/kg. There was a reduction in xylene-edema index, with Fr40 (25 mg/kg), AEEm (50 mg/kg) and Fr20 (50 mg/kg). All doses of AEEm, Fr20, and Fr40 reduced both phases of the formalin model. In the abdominal contortion model, Fr40 presented the highest activity, reducing 96% of contortions and its antinociceptive mechanism was evaluated. The results indicated the involvement of NO and adrenergic activation pathways. The main components of Fr40 are swertisin, swertiajaponin, isoorientin 7,3′-dimethyl ether, swertisin-O-rhamnoside, isoorientin, isovitexin, isovitexin-Orhamnoside, and isovitexin-7-O-glucoside. The aqueous extract of E. macrophyllus leaves and its fractions exhibited significant analgesic effect, mediated through both peripheral and central mechanisms being considered a potentially antinociceptive drug.

Anti-nociceptive Potential of Ethanol Extract of Terminalia macroptera Guill&amp;Perr (Combretaceae) Stem Bark in Mice

Background: Terminalia macroptera Guill. &amp;Perr. (Combretaceae) is a flowering plant with several ethno-medicinal claims. However, the dearth of information on its analgesic property has necessitated this study.Objectives: to evaluate the anti-nociceptive potential of ethanol extract of Terminalia macroptera stem bark (TMSB) in mice.Materials and Methods: Male and female mice of weight range 22 – 25g were randomly allotted into seven groups (n= 5) and treated as follows: Group I received 0.5 mL distilled water orally (negative control), Groups II-V were orally administered ethanol extract of T. macroptera stem bark (TMSB) at 50, 100, 200, and 400 mg/kg respectively while groups VI-VII received piroxicam 10 mg/kg and pentazocine 2 mg/kg intraperitoneally respectively as standards. The same treatment pattern was adopted for both pain models: tail immersion and acetic acid-induced writhing assays. Data were expressed as mean ± standard error of mean (SEM) using two-way analysis of variance (ANOVA) followed by Tukey’s and Bonferroni's multiple comparisons tests with p &lt; 0.05 taken as significance.Results: The ethanolic extract of Terminalia macroptera stem bark showed significant dose-dependent anti-nociceptive activity at 100 and 400 mg/kg (2.95±0.41 and 2.9±0.31 respectively) 60 min post-treatment compared to the negative control group in the tail immersion test. Significant inhibition of nociception (0.20±0.20) was obtained at 400 mg/kg compared to the negative control group in the acetic acid-induced writhing test.Conclusions: The ethanol extract of Terminalia macroptera stem bark exhibited dose-dependent anti-nociceptive potential in both tail immersion and acetic acid-induced writhing assays in mice.

Pharmacological evaluation of the gabapentin salicylaldehyde derivative, gabapentsal, against tonic and phasic pain models, inflammation, and pyrexia.

Gabapentinoids are effective drugs in most animal models of pain and inflammation with variable effects in humans. The current study evaluated the pharmacological activity of gabapentin (GBP) and its salicylaldehyde derivative (gabapentsal; [2-(1-(((2-hydroxybenzylidene) amino) methyl) cyclohexyl) acetic acid]; GPS) in well-established mouse models of nociceptive pain, inflammatory edema, and pyrexia at doses of 25-100 mg/kg. GPS allayed tonic visceral pain as reflected by acetic acid-induced nociception and it also diminished thermally induced nociception as a mimic of phasic thermal pain. Antagonism of GPS-induced antinociceptive activities by naloxone (NLX, 1.0 mg/kg, subcutaneously, s.c), beta-funaltrexamine (β-FNT, 5.0 mg/kg, s.c), naltrindole (NT, 1.0 mg/kg, s.c), and nor-binaltorphimine (NOR-BNI, 5.0 mg/kg, s.c), and pentylenetetrazole (PTZ-15 mg/kg, intraperitoneally, i.p) implicated an involvement of both opioidergic and GABAergic mechanisms. Tail immersion test was conducted in order to delineate the mechanistic insights of antinociceptive response. Inflammatory edema induced by carrageenan, histamine, or serotonin was also effectively reversed by GPS in a fashion analogous to aspirin (150 mg/kg, i.p), chlorpheniramine (1.0 mg/kg, i.p), and mianserin (1.0 mg/kg, i.p), respectively. Additionally, yeast-induced pyrexia was decreased by GPS in a comparable manner to acetaminophen (50 mg/kg, i.p). These observations suggest that GPS possesses ameliorative properties in tonic, phasic, and tail immersion tests of nociception via opioidergic and GABAergic mechanisms, curbs inflammatory edema, and is antipyretic in nature.