Antinociceptive Effect of Ethanolic Extract of Codiaeum variegatum Leaves in Mice

Background: Codiaeum variegatum, sometimes called garden croton, is a tropical plant in the Euphorbiaceae family. Historically used to cure various conditions, including intestinal infections, fever, ulcers, wounds, and gonorrhea. This work aimed to investigate the antinociceptive effects of ethanolic extract of Codiaeum variegatum leaves (EECV) in animal models. Methods: Five different pain models—the hot plate, tail immersion, acetic acid-induced writhing, formalin, and glutamate-induced nociception tests—were utilized to assess the antinociceptive activity in mice. The traditional drugs such as diclofenac sodium (10 mg/kg, i.p.) and morphine sulphate (5 mg/kg). EECV was administered orally at varying doses of 100, 200, and 300 mg/kg (0.1 mL/mouse), while the control group was given deionized water. Results: The current study found that all mouse models of heat- and chemical-induced pain had robust EECV reflections of their antinociceptive properties (*p Conclusions: The current finding offers a fresh perspective on the ethanolic extract of Codiaeum variegatum leaves’ antinociceptive properties in mice. This plant’s phytochemical analysis revealed the presence of triterpenoids, sterols, alkaloids, flavonoids, and general glycosides, all of which may have antinociceptive properties. More research on the mechanism of action and associated pharmacological studies, such as in vivo analysis, medication formulation, and clinical trials, is strongly advised.

Antinociceptive Effect of Methanol Extract of Diospyros malabarica (Desr.) Kostel Leaves in Mice

Background: Diospyros malabarica (Desr.) Kostel, a small to medium-sized tree in the Ebenaceae family, is known as “Deshi Gab” in Bangladesh. Fever, diabetes, snake bite, diarrhea, biliousness, and ulcer ailments are all treated with the herb. This study’s goal was to examine in mouse models the antinociceptive properties of methanol extract of Diospyros malabarica leaves (MEDM). Methods: For the purpose of determining the antinociceptive activity in mice, five distinct pain models including hot plate, tail immersion, acetic acid-induced writhing, formalin and glutamate-induced nociception tests were used. The conventional medications were morphine sulphate (5 mg/kg, intraperitoneally) and diclofenac sodium (10 mg/kg, intraperitoneally). While the control group was expecting deionized water, MEDM was given orally at dosages of 200, 400, and 600 mg/kg (0.1 mL/mouse, orally). Results: According to the current research, MEDM strongly reflected the antinociceptive activity of all mouse models of chemical and heat-induced pain (*p < 0.05). 400 and 600 mg/kg demonstrated a considerable (*p < 0.05) ability to prolong the reaction of latency to pain in opposition to thermally produced nociception in hot plate and tail immersion tests. Inhibition levels in the acetic acid-induced writhing test were 11.57%, 37.77%, and 51.83%, respectively. The extract suppressed 20.78%, 45.48%, and 56.93% of licking during the initial stages of formalin-induced nociception. In the late phase, the extract showed higher rates of licking than the control group (13.14%, 50.28%, and 66.85%). The glutamate-induced nociception test was significantly (*p < 0.05) prevented by the plant extract. Compared to the control, it demonstrated an inhibition of licking of 22.85%, 47.32%, and 63.42%, respectively. Conclusions: It is evident that the plant extract has exceptional analgesic properties. To determine the precise processes behind antinociceptive effect and to identify the substances that produce this activity, more research is required. The study’s findings also support the long-standing use of MEDM in painful conditions.

Antinociceptive activity of Ricinus communis L.leaves

Objective:To evaluate the antinociceptive activity of the methanol extract of Ricinus communis leaves(MRCL).Methods:Antinociceptive activity was evaluated using acetic acid induced writhing test,formalin induced paw licking and tail immersion method in mice at doses of 100,125 and 130 mg/kg bw.Results:The results indicated that MRCL exhibited considerable antinociceptive activity against three classical models of pain in mice.Preliminary phytochemical analysis suggested the presence of saponin,steroids and alkaloids.Conclusions:It can be concluded that MRCL possesses antinociceptive potential that may be due to saponin,steroids and alkaloids in it.

In vivo screening of essential oils of Skimmia laureola leaves for antinociceptive and antipyretic activity

Objective:To study the screening of essential oils of Skimmia laureola leaves(SLO)for acute toxicity,antinociceptive,antipyretic and anticonvulsant activities in various animal models.Methods:SLO were extracted using modified Clevenger type apparatus.Acute toxicity test was used in mice to observe its safety level.Antinociceptive activity of SLO was evaluated in acetic acid induced writhing and hot plate tests.Yeast induced hyperthermic mice and pentylenetetrazole induced convulsive mice were used for the assessment of its antipyretic and anticonvulsant profile respectively.Results:Substantial safety was observed for SLO in acute toxicity test.SLO showed a high significant activity in acetic acid induced writhing test in a dose dependent manner with maximum pain attenuation of 68.48%at 200 mg/kg i.p.However,it did not produce any relief in thermal induced pain at test doses.When challenged against pyrexia evoked by yeast,SLO manifested marked amelioration in hyperthermic mice,dose dependently.Maximum anti-hyperthermic activity(75%)was observed at 200 mg/kg i.p.after 4 h of drug administration.Nevertheless,SLO had no effect on seizures control and mortality caused by pentylenetetrazole.Conclusions:In vivo studies of SLO showed prominent antinociceptive and antipyretic activities with ample safety profile and thus provided pharmacological base for the traditional uses of the plant in various painful conditions and pyrexia.Additional detail studies are required to ascertain its clinical application.

Mechanisms of antinociceptive effects of ouabain in combination with neostigmine in the rat

BACKGROUND： It has been previously shown that intrathecal administration of either ouabain or neosdgmine can produce antinociceptive effects. Moreover, ouabain and neostigmine are differently associated with acetylcholine. OBJECTIVE： It has been hypothesized that intrathecal administration of ouabain, in combination with neostigmine, can produce antinociceptive synergistic effects. Atropine, as a competitive antagonist, was pre-injected to verify the mechanisms of action. DESIGN, TIME AND SETTING： This study was a randomized, controlled, animal experiment, performed at the State Key Laboratory of Oncology in Southern China between May 2006 and February 2007. MATERIALS： A total of 102 healthy, adult, Sprague Dawley rats were included. Ouabain and neostigmine （Sigma, USA）, as well as atropine （Tanabe Seiyaku, Japan）, were also used. METHODS： Varied doses of ouabain, neostigmine, and a combination of the two were intrathecally injected into rats. Six rats were allotted for each dose group. Intrathecal pretreatment with atropine was tested 10 minutes prior to intrathecal administration of neostigmine or the combination of ouabain and neostigmine. MAIN OUTCOME MEASURES： Tail-flick tests were performed to measure tail-flick latency （seconds） prior to and after administration. The response in the tail-flick test was expressed as the percentage of maximum possible effect （% MPE）, where % MPE = [tail-flick latency after administration （seconds） -mean baseline value for tail-flick latency]/[ 10 seconds - the mean baseline value for tail-flick latency （seconds）] x 100%. RESULTS： Rat spinal intrathecal administration of either ouabain or neostigmine alone produced antinociceptive effects in a dose-dependent manner. Intrathecally administration of neostigmine （0.05, 0.1, 0.3 μg ） in combination with ouabain （1 μ g ） produced enhanced antinociceptive effects, with a % MPE of 29%, 78%, and 95%, respectively （P 〈 0.05）. Intrathecally administration of 0.3μg neostigmine （% MPE： 45%）, in combination with 1 μ g ouabain （% MPE： 27%） produced potent antinociceptive effects （% MPE： 95%）. Intrathecally pre-injected atropine antagonized the antinociceptive effects of neostigmine （3 μg）, or a combination of ouabain （1 μg） and neostigmine （0.3 μg） （P 〈 0.01）. CONCLUSION： Rat spinal intrathecal administration of either ouabain or neostigmine alone produced dose-dependent andnociceptive effects. Ouabain enhanced the antinociceptive effects of neostigmine. Atropine antagonized the antinociceptive effects of neostigmine or the combination of ouabain and neostigmine. This occurs possibly due to the fact that atropine is a competitive antagonist of the muscarinic acetylcboline receptors.

Estimation of the novel antipyretic, anti-inflammatory, antinociceptive and antihyperlipidemic effects of silymarin in Albino rats and mice

Objective: To evaluate the other pharmacological actions of silymarin in Albino rats and mice such as antipyretic, anti-inflammatory, antinociceptive and antihyperlipidemic effects. Methods: Rats were injected intramuscularly with pyrogenic dose of brewer's yeast for the antipyretic test of silymarin. Another group of rats injected with 0.1 mL of 1% carrageenan solution in saline at the subplanter area of the right hind paw for the anti-inflammatory test of silymarin. Another group of mice tested by hot plate method for determination of antinociceptive effect of silymarin. Hyperlipidemia was induced using high fat diet for 2 months to estimate the antihyperlipidemic activity of silymarin. Results: Silymarin showed a significant antipyretic effect of both doses(50 and 100 mg/kg) compared with control untreated group. Moreover, silymarin elucidated a significant anti-inflammatory effect of both doses reflected on the decrease of the rat paw edema every hour interval for 4 h after administration in comparison with control positive group. By the same taken, both doses of silymarine revealed a significant antinociceptive action in hot plate method at 30 and 60 min post administration. Besides, it lowered significantly the serum levels of prostaglandin E2, tumor necrosis factor alpha and interleukin 1 beta after 2 h of silymarin administration in carrageenan induced rat paw edema besides the significant decrease of total cholesterol, triglycerides, low density lipoprotein and significantly elevated high density lipoprotein after 2 weeks of silymarin administration. Conclusions: These outcomes delivered a new vision into the possible pharmacological mechanisms by which silymarin advances antipyretic, anti-inflammatory, antinociceptive and antihyperlipidemic effects.

Antinociceptive and anti-inflammatory activities of crude extracts of Ipomoea involucrata leaves in mice and rats

Objective:To investigate antinociceptive and anti-inflammatory activities of crude extract from Ipomoea involucrata leaves(Convolvulaceae) in mice and rats.Methods:The antinociceptive activity was tested using acetic acid-induced abdominal writhing test in mice.The antiinflammatory activity was evaluated using egg albumin -induced oedema of rat paw.Results: Phytochemical screening showed the presence of alkaloids,flavonoids,saponins,terpenoids and tannin.At the doses of 25-100 mg/kg,Ipomoea involucrata exhibited dose-dependent and significant increase in pain threshold in acetic acid -induced writhing test of mice (P【0.05,student t-test) The administration of Ipomoea involucrata leaf extract(25-100 mg/ kg) showed dose-dependent decreases in paw volume of egg albumin induced oedema in rats and a significant higher anti-inflammatory activity compared to the standard control(Aspirin). Conclusions:These results support the claims on the traditional use of the of Ipomoea involucrata leaves in the treatment of toothache,rheumatic pains and other inflammatory conditions.Studies on the isolation and structural elucidation of the active principle are still needed being carried out.

Anti-inflammatory and antinociceptive activities of Rhipicephalus microplus saliva

To evaluate the antinociceptive and anti-inflammatory activities and the toxic effects of Rlhipicephalus microplus saliva for elucidating the modulation mechanism between arthropod saliva and host.Methods:For saliva collection,engorged ticks were obtained from a controlled bovine infestation and collected by natural fall.The ticks were fixed and injected pilocarpine 0.2%for induction of salivation.Saliva was collected,lyophilized and stored at-80℃.Cytotoxic activity was assessed by the hemolysis method(25,50,100,200 and 300μg/mL)and MTT cell viability assay(2.5,5,10,20 and 40μg/mL)for 24,48 and 72 h.Anti-inflammatory activity was evaluated using the method of neutrophil migration to the peritoneal cavity of mice at doses of l0,15 and 20 mg/kg;antinociceptive activity was assessed using the acetic acid-induced writhing test,and formalin-induced paw-licking in mice at dose of 15 mg/kg.Results:Saliva did not cause erythrocytes hemolysis at any concentration tested,as well as did not decrease cell viability in the MTT assay.Saliva inhibited neutrophil migration by 87%and 73%at doses of l5 and 20 mg/kg,respectively.In the nociceptive tests,saliva presented analgesic activity of69.96%in the abdominal writhing test,and of 84.41%in the formalin test.The study proves that Rlhipiceplhalus microplus saliva has significant in vivo anti-inflammatory and antinociceptive activities.The data presented herein support the development of further studies to elucidate the active principles of Rhipicephalus microplus saliva and its mechanism of action and,in future,to develop novel anti-inflammatory and analgesic drugs.

Pentapeptide Any-GS Blocks Antinociceptive Effect of Poneratoxin in Rats

Poneratoxin （PoTX） is an insect neuropeptide isolated from ant venom. It was previously demonstrated that administration of synthetic PoTX into the lateral brain ventricle （icv） induced in rats significant antinociceptive effect. Moreover it was demonstrated that this effect was not mediated by opioid receptors. The aim of present study was to determine other probable mechanisms mediating antinociceptive effect of PoTX, above all： （1） to check if insect-derived pentapeptide Any-GS may influence on PoTX-induced analgesia in rats, and （2） to estimate the role of voltage-gated sodium channels in rat＇s brain in antinociceptive effect of PoTX. The study was performed on adult, female wistar rats, which a week before experiments were implanted with polyethylene cannulas into the lateral brain ventricle （icv）. Antinociceptive effect of PoTX applied directly icv was determined in rats by the test of the tail immersion. PoTX applied icv at the dose of 1 or 5 nmol induced significant antinociceptive effect in rats. Pretreatment rats with equimolar dose of 1 or 5 nmol of veratridine, an agent, which opens voltage-gated sodium channels in neurons of rat brain, did not modify effect of PoTX. On the other hand, prior icv administration of pentapeptide Any-GS significantly inhibited antinociceptive effect of both icv doses of 1 and 5 nmols of PoTX. The results of the present study demonstrated antagonistic effect Any-GS against PoTX-induced analgesia. Thus blocking effect Any-GS on PoTX-induced analgesia indicates that this insect peptide is a probable antagonist of PoTX.

Antinociceptive and Anti-inflammatory Activities of Methanol Extract of Ormosia coccinea （Aubl,） Jacks in vivo

The present study was conducted to evaluate the antinociceptive and anti-inflammatory activities of methanol extract of rachis of Ormosia coccinea （Aubl.） Jacks （MEOC） using animal models of nociception and inflammation. The antinociceptive activity of the extract was assessed using acetic acid-induced abdominal writhing, hot-plate, and formalin tests. Oral administration of MEOC （500 mg/kg） produced significant （t7 〈 0.05） antinociceptive effects when tested in mice using acetic acid-induced abdominal writhing test and on the inflammatory phase of the formalin test. It was also demonstrated that MEOC had no significant effect on the response latency time to the heat stimulus in the thermal model of the hot plate test. The anti-inflammatory activity of the extract was assessed using carrageenan, histamine and serotonin induced oedema in rat paw. The oral administration of MEOC showed maximum inhibition （64.29%） at 1 h on carrageenan edema, but it did not modify the edema induced by histamine and serotonin. The present results suggest that MEOC has a peripheral antinoeiceptive and anti-inflammatory action.

THE ROLE OF BRAIN-STEM DISCENDING INHIBITORY SYSTEM IN THE ANTINOCICEPTIVE EFFECT ELICITED BY MUSCLE SPINDLE AFFERENTS

Objective To analyse the antinociceptive effect of muscle spindle afferents and the involved mechanism.Methods The single unit of wide dynamic range neurons in the spinal cord dorsal horn were recorded extracelluarly.The effects of muscle spindle afferents elicited by intravenous administration of succinylcholine on nociceptive responses (C fibres evoked responses,C responses) of WDR neurons were observed before and after bilateral lesions of ventrolateral periaqueduct gray .And the effects of muscle spindle afferents on the spontaneous discharge of the tail flick related cell in the rostral ventro medial medulla and on the spontaneous discharge of the PAG neurons were observed.Results The C responses of WDR neurons were significantly inhibited by muscle spindle afferents,and the inhibitory effects were reduced by bilateral lesions of ventrolateral PAG.The spontaneous discharge of the off cell in the RVM was excited while the on cell was inhibited by intravenous administration of Sch.The spontaneous discharge of the PAG neurons were excited by muscle spindle afferents.Conclusion Muscle spindle afferents show a distinct effect of antinociception.PAG RVM descending inhibitory system may play an important role in this nociceptive modulative mechanism.

THE ROLE OF NUCLEUS RAPHE MAGNUS IN THE ANTINOCICEPTIVE EFFECT OF MUSCLE SPINDLE AFFERENTS IN THE RAT

Objective To investigate the role of NRM in the antinociceptive effect of muscle spindle afferents,the influence of NRM lesion on the inhibitory effect of muscle spindle afferents on the nociceptive responses of wide dynamic range (WDR) neurons and the effects of the muscle spindle afferents on the NRM neuronal activities were observed. Methods The single units of WDR neurons in the spinal dorsal horn were recorded extracellularly, and the inhibitory effects of activating muscle spindle afferents by intravenous administration of succinylcholine (SCH) on the C fibers evoked responses (C responses) of WDR neurons were tested before and after lesion of NRM.The effects of the muscle spindle afferents activated by administrating SCH on the single NRM neurons were also examined.Results ①It was found that the C responses of WDR neurons were significantly inhibited by intravenously administration of SCH, and the inhibitory effect was reduced after lesion of NRM;②The activities of most of the NRM neurons could be changed significantly by administrating SCH. According to their responses, NRM neurons could be classified into three types:excitatory, inhibitory and non responsive neurons, and the responses were dose dependent. Conclusion These results suggest that the muscle spindle afferents evoked by SCH may activate the NRM neurons, which plays an important role in the antinociception of muscle spindle afferents.

Nitridergic Modulation of the Antinociceptive Activity of Rosuvastatin in Mice

Statins, 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase enzyme inhibitors, are lipid-lowering drugs, often used in the treatment of cardiovascular diseases (hyperlipidemia, atherosclerosis). It has been shown that statins have antiinflammatory effects independent of their lipid-lowering effects and these anti-inflammatory effects inhibit the inflammation and pain process. This study evaluated the antinociceptive and anti-inflammatory effects of rosuvastatin using the acetic acid writhing, the formalin hind paw, the orofacial formalin and the hot plate tests. The following experimental group were used: control, acute (1 day) and chronic (3 days) after oral gavage with rosuvastatin (3, 10, 30, 100 and 300 mg/kg). Rosuvastatin produced a dose-dependent antinociception, with different potency, in all the tests. Additionally, nitric oxide synthase inhibitors (Abbreviationsand aminoguanidine) were used to assess the nitric oxide participation on this induced rosuvastatin antinociception. The data demonstrated the antinociceptive and anti-inflammatory activity of rosuvastatin in algesiometer models of tonic or phasic pain. These activities seem to be induced by modulation of iNOS expression, a result that may be relevant in the pharmacological treatment of human pain where rosuvastatin and nitric oxide synthase inhibitors must be used.

Evaluation of Antinociceptive and Anti-Inflammatory Effects of Synthetic O-Prenylated Phenolic Derivatives

This work describes the synthesis, antinociceptive and anti-inflammatory effect of O-prenyl derivatives: O-prenyl derivatives 2-(3-methylbut-2-enyloxy)acetophenone (L1) and 3-methoxy-4-(3-methylbut-2-enyloxy)benzaldehyde (V1). Treatment with L1- or V1-produced antinociceptive effect on classical pain models: acetic acid abdominal contortions and formalin test (first and second phases), and in hot plate or tale flick models in mice without changing the locomotors performance, and anti-oedematogenic or anti-inflammatory effect in vivo: carrageenan-induced paw oedema and peritonitis in mice. In addition, L1 and V1 derivatives reduced nitric oxide production on RAW 264.7 cells stimulated with lipopolysaccharide without changing the cell viability. Taken together, our results show for the first time that L1 and V1 can produce antinociception and modulate inflammatory response when administered in mice.

Comparative study of chemical composition, antinociceptive effect and acute toxicity of the essential oils of three Asarum drugs

In the present study, the chemical composition, antinociceptive effect and acute toxicity of essential oils（EOs） of Asarum heterotropoides Fr. Schmidt var. mandshuricum（Maxim.） Kitag.（AHM）, A. sieboldii Miq. var. seoulense Nakai（ASS） and A. himalaicum Hook. f. et Thoms. ex Klotzsch.（AH） were comparatively evaluated. A total of 55 compounds were identified in EOs of AHM, ASS and AH by GC-MS. Methyleugenol（20.16%–62.89%）, safrole（2.67%–32.42%）, 3,5-dimethoxytoluene（2.00%–18.59%） and eucarvone（1.52%–19.16%） were the major constituents of EO of AHM, and methyleugenol（48.35%–61.06%）, eucarvone（11.13%–13.93%） and elemicin（4.79%–11.14%） were the major constituents of EO of ASS. The EO of AH was different from that of AHM and ASS, in which patchouli alcohol（27.42%–51.95%） and elemicin（13.11%–42.23%） were found in a greater amount. Moreover, the antinociceptive effect of EOs of AHM（5.5, 11.0, 16.5 μL/kg） and AH（2.0, 4.0, 6.0 μL/kg） was comparatively assayed in acetic acid-induced writhing, hot plate and formalin tests. The results indicated a weak central, but potent peripheral antinociceptive effect of EO of AHM, and more potent central and peripheral antinociceptive effect of EO of AH. The LD50 of the EOs of AHM and AH were 1.7 and 7.7 mL/kg, respectively. These findings suggest that EOs of AHM and AH possess evident antinociceptive activity and are probably safe within the range of its clinical doses. However, their chemical compositions are quite different. Therefore, AH can be clinically used as an herbal medicinal product with broad analgesic effects, but should not be confused with AHM and ASS used in traditional Chinese medicine.

Antinociceptive grayanane-derived diterpenoids from flowers of Rhododendron molle

Twelve new grayanoids(1-12)along with five known compounds were isolated from flowers of Rhododendron molle.Their structures were fully characterized using a combination of spectroscopic analyses,computational calculations,and single crystal X-ray diffraction.Rhomollone A(1)possesses an unprecedented 5/6/6/5 tetra-cyclic ring system(B-nor grayanane)incorporating a cyclopentene-1,3-dione scaffold.Rhodomollein XLIII(2)is a dimeric grayanoid,containing a novel 14-membered heterocyclic ring with a C2 symmetry axis.The antinociceptive activities of compounds 3,4,6,7,and 12-17 were evaluated by an acetic acid-induced writhing test.Among them,compounds 3,7,12,15 and 16 displayed significant antinociceptive activities at a dose of 20 mg/kg with inhibition rates ranging from41.9%to 91.6%.Compounds 6 and 13 inhibited 46.0%and 39.4%of the acetic acid-induced writhes at a dose of 2 mg/kg,while compound 17 inhibited 34.3%of the writhes at a dose of 0.4 mg/kg.

Sedative and antinociceptive activities of two new sesquiterpenes isolated from Ricinus communis

Two new sesquiterpenes, trivially named ricinusoids A(1) and ricinusoids B(2), were isolated from ethyl acetate fraction of Ricinus communis. The structures of new compounds were elucidated by detailed spectroscopic techniques, including 1 D-and 2 D-NMR, UV, IR spectroscopy, and mass spectrometry. The compounds(1-2) were also assessed for in-vivo sedative and analgesic like effects in open field and acetic acid induced writhing tests respectively at 5, 10, and 20 mg·kg^(–1) i.p. Pretreatment of both test compounds caused significant(P ≤ 0.05) reduction in locomotive activity like sedative agents and abdominal constrictions like analgesics. Both compounds(1-2) possessed marked sedative and antinociceptive effects in animal models.

Quantitative Electrophysiological Evaluation of the Analgesic Efficacy of Two Lappaconitine Derivatives: A Window into Antinociceptive Drug Mechanisms

Quantitative evaluation of analgesic efficacy improves understanding of the antinociceptive mechanisms of new analgesics and provides important guidance for their development.Lappaconitine(LA),a potent analgesic drug extracted from the root of natural Aconitum species,has been clinically used for years because of its effective analgesic and non-addictive properties.However,being limited to ethological experiments,previous studies have mainly investigated the analgesic effect of LA at the behavioral level,and the associated antinociceptive mechanisms are still unclear.In this study,electrocorticogram(ECoG)technology was used to investigate the analgesic effects of two homologous derivatives of LA,Lappaconitine hydrobromide(LAH)and Lappaconitine trifluoroacetate(LAF),on Sprague-Dawley rats subjected to nociceptive laser stimuli,and to further explore their antinociceptive mechanisms.We found that both LAH and LAF were effective in reducing pain,as manifested in the remarkable reduction of nocifensive behaviors and laser-evoked potentials(LEPs)amplitudes(N2 and P2 waves,and gamma-band oscillations),and significantly prolonged latencies of the LEP-N2/P2.These changes in LEPs reflect the similar antinociceptive mechanism of LAF and LAH,i.e.,inhibition of the fast signaling pathways.In addition,there were no changes in the auditory-evoked potential(AEP-N1 component)before and after LAF or LAH treatment,suggesting that neither drug had a central anesthetic effect.Importantly,compared with LAH,LAF was superior in its effects on the magnitudes of gamma-band oscillations and the resting-state spectra,which may be associated with their differences in the octanol/water partition coefficient,degree of dissociation,toxicity,and glycine receptor regulation.Altogether,jointly applying nociceptive laser stimuli and ECoG recordings in rats,we provide solid neural evidence for the analgesic efficacy and antinociceptive mechanisms of derivatives of LA.

In vivo hypoglycemic, antinociceptive and in vitro antioxidant activities of methanolic bark extract of Crataeva nurvala

Objective: To rationalize the folkloric use of hypoglycemic, antinociceptive and antioxidant potentials with phytochemical screening of methanolic bark extract of Crataeva nurvala (C. nurvala) in vivo and in vitro. Methods: The collected bark was dried and grinded. The coarse powder was soaked in 2000 mL of 90% methanol for several days then filtrated. At 40 °C the volume of crude methanolic extract (CME) was reduced by a vacuum rotary evaporator, then the aqueous methanol extract was separated into petroleum ether, carbon tetrachloride, and aqueous soluble fractions by Kupchan protocol. Then the extracts were subjected to evaluate in vivo analgesic, hypoglycemic activities in Swiss albino mice model and antioxidant in vitro. Results: In quantitative phytochemical analysis, total phenolic content was found maximum (235.94 mg of GAE/g) in aqueous soluble fraction;in case of antioxidant potentials, DPPH free radical scavenging assay showed IC50 value of 9.25 μg/mL exhibited by aqueous soluble fraction in comparison to ascorbic acid (8.27 μg/mL) as a reference standard. The CMEs potentially (P < 0.05) reduced the acetic acid-induced writhing and increased (P < 0.05;P< 0.01) latency period in the tail immersion method at a dose dependent manner. The CME significantly reduced blood sugar level of diabetic rat induced by alloxan monohydrate. Conclusions: This study was conducted to validate the extensive use of C. nurvala bark as folk medicine with antinociceptive, hypoglycemic and antioxidant effects. It can be concluded that the bark of C. nurvala possesses good antinociceptive, moderate hypoglycemic and antioxidant activities. However, further chemical and pharmacological revise are needed to elucidate the detail mode of action behind this and identify the responsible active principles.

Intrathecal administration of neuronostatin induces an antinociceptive effect in a mouse visceral pain model

Neuronostatin(NST)is a peptide encoded by the somatostatin gene that serves important physiological functions in diverse tissues.Previous studies have shown that intracerebroventricular administration of NST induces antinociceptive effects and hyperalgesic effects as determined by the tail immersion assay and formalin test,respectively.In the present study,we aimed to evaluate the effects of intrathecal(i.t.)injection of NST on nociception in a model of visceral pain,and determine possible mechanisms of action in mice.NST(1,3,6,or 12 nmol)was administered to mice,leading to a dose-dependent antinociceptive effect as determined by the acetic acid-induced writhing test in mice.NST(1 nmol)also enhanced the antinociceptive effect of morphine(2.5 and 5μg/kg)in the spine.Naloxone andβ-funaltrexamine hydrochloride significantly antagonized the antinociceptive effect of NST.The expression of G-protein-coupled receptor 107(GPR107)protein and the phosphorylation of PKA at Thr197 were increased after i.t.administration of NST,suggesting that theμ-opioid receptor and GPR107/PKA signaling pathway are involved in the analgesic response.In conclusion,i.t.injection of NST may potentially be used as a new approach in the mediation of visceral pain.