Central Antinociceptive Effect Research Articles

In vivo evaluation of the antinociceptive effects of novel methylsulfonyl group-containing compounds.

Pain management is among the problems that remain important today, and analgesic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, tricyclic antidepressants, and anticonvulsants used in pain treatment cause various side effects. Therefore, new, safe, and highly effective drugs are needed. Synthesis of chemical molecules has begun to be preferred as a faster and easier method in new drug development processes. In this study, new compounds (3a-3k) containing the "methylsulfonyl group," which have been shown to have potential inhibitory effects on cyclooxygenase (COX) enzymes responsible for the synthesis of inflammatory mediators, were synthesized. Central antinociceptive effect of the compounds was evaluated by hot-plate and tail-immersion tests, and the peripheral antinociceptive effect was evaluated by acetic acid-induced writhing test. 3a, 3b, 3d, 3e, 3f, 3g, 3h, 3i, 3j, and 3k (20 mg/kg) significantly increased the percentage of themaximum possible effect (MPE %) in the hot-plate test compared to the control group. 3a-3k (20 mg/kg) significantly increased MPE % in the tail-immersion test compared to the control group and significantly decreased the number of writhings in the acetic acid-induced writhing test. The results of this study indicate that the synthesized compounds containing methylsulfonyl groups have central and peripheral antinociceptive effects.

Novel chimeric peptides of endomorphin-2 and the active fragments of ghrelin exhibit blood-brain barrier permeability and central antinociceptive effects with reduced opioid-related side effects

Novel chimeric peptides of endomorphin-2 and the active fragments of ghrelin exhibit blood-brain barrier permeability and central antinociceptive effects with reduced opioid-related side effects

Mechanisms of action of ethyl acetate fractions of Liparis nervosa (Thunb.) Lindl. as potential central anti-nociceptive agents.

Opioids/non-steroidal anti-inflammatory drugs are used to alleviate pain; however, they are expensive and can have adverse effects, especially when used over extended periods. Therefore, there is immense demand for innovative, non-addictive analgesics. Here, we report a novel plant-derived central anti-nociceptive agent, Liparis nervosa (Thunb.) Lindl. (LN), validated in animal pain models. Ethyl acetate fractions of L. nervosa (EALN) exhibited central anti-nociceptive activity in hot plate, tail immersion, formalin-induced paw oedema, and acetic acid-induced abdominal writhing tests. The chemical composition of the EALN was determined using ultra-high-performance liquid chromatography-mass spectrometry. Reserpine (monoamine transmitter-depleting agent) and naltrexone (opioid antagonist) partially suppressed the anti-nociceptive effect of EALN in both phases of the formalin test. Oral administration of EALN activated the endogenous opioid and central descending inhibitory systems by increasing β-endorphin, 5-hydroxytryptamine, and norepinephrine expression. EALN treatment increased the expression of γ-aminobutyric acid B; inhibited the expression of prostaglandin E2, substance P, calcitonin gene-related peptide, and c-Fos; and blocked the transmission of pain signals in the spinal cord. EALN treatment reduced the activity of nitric oxide and nitric oxide synthase in the central region and inhibited the nitric oxide-cyclic guanosine monophosphate signal transduction pathway, thereby attenuating the transmission of nociceptive information in the descending inhibitory pathways. The central anti-nociceptive effect of EALN was achieved by integrating these pathways. This study provides new insights into the pharmacologic action of LN and provide a therapeutic approach as a promising candidate for central anti-nociceptive agents.

Structure-Activity Relationship of 7-Chloro-4-(Phenylselanyl) Quinoline: Novel Antinociceptive and Anti-Inflammatory Effects in Mice.

The 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) shows promise for its antinociceptive and anti-inflammatory properties. Here, we explored the structure-activity relationship of 4-PSQ and its analogues: 7-chloro-4-[(4-fluorophenyl) selanyl]quinoline (a), 7-chloro-4-{[3-trifluoromethyl)phenyl] selanyl} quinoline (b), 4-((3,5-Bis(trifluoromethyl)phenyl) selanyl-7-chloroquinoline (c), 7-chloro-4-[(2,4,6-trimethyl)selanyl]quinolinic acid (d) and 7-chloroquinoline-4-selenium acid (e) in models of acute inflammation and chemical, thermal and mechanical nociception in mice, alongside in silico analysis. Compounds a (-F), b (-CF3), c (-Bis-CF3), d (-CH3), e (-OOH), and 4-PSQ exhibited antinociceptive effects in chemical and thermal nociception models, except d (-CH3) and e (-OOH) in the hot plate test. None induced locomotor changes. In silico, only c (-Bis-CF3) showed low gastrointestinal absorption, and c (-Bis-CF3) and e (-OOH) lacked blood-brain barrier penetration, suggesting e (-OOH) lacked central antinociceptive effect. These compounds had higher COX-2 affinity than COX-1. Our findings suggest substituent insertion alters 4-PSQ's efficacy as an antinociceptive and anti-inflammatory agent.

Bioflavonoid exerts analgesic and anti-inflammatory effects via transient receptor potential 1 channel in a rat model.

Pain is an uncomfortable sensation in the body. Kaempferol is a flavonoid with antinociceptive effects. Transient receptor potential (TRP) channels have been characterized in the sensory system. This study evaluated the central antinociceptive effect of Kaempferol and possible mechanisms of action of transient receptor potential cation channel subfamily V member 1 (TRPV1). Capsaicin as a TRPV agonist (5 μg/μL, intracerebroventricular [ICV]) and capsazepine as its antagonist (10 μg/μL, icv) were used to test the analgesic effect of kaempferol (1.5 mg, ICV). Morphine (10 μg, ICV) was used as a positive control. The other groups were treated with a combination of kaempferol and capsaicin, kaempferol and capsazepine, and capsaicin and capsazepine. The cannula was implanted in the cerebroventricular area. The tail-flick, acetic acid, and formalin tests were used to assess analgesic activity. For evaluation of antiinflammatory effect, the formalin-induced rat paw edema was used. Kaempferol significantly decreased pain in the acute pain models, including the tail-flick and the first phase of the formalin test. In the late phase of the formalin test, as a valid model of nociception, capsazepine inhibited the antinociceptive effect of kaempferol. Kaempferol has an analgesic effect in the acute pain model and can affect inflammatory pain. Also, the TRPV1 channel plays a role in the antinociceptive activity of kaempferol.

In-vivo Anticonvulsant and Analgesic Activities of Sclareol Isolated from Salvia officinalis L

Salvia officinalis, a native plant to the Mediterranean and Middle East, is familiar cookery and traditional herb. Herein, in vivo anticonvulsant and analgesic effects of sclareol isolated from S. officinalis were reported. Sclareol (50 mg/kg) decreased tonic convulsions from 100% (positive control) to 33.33% with 16.66% mortality using MES protocol. Also, 100 mg/kg decreased convulsions to 16.66%, with no mortality. In MEST test, sclareol protected against gradually increased electric shock in a dose-dependent manner comparable to phenytoin. Pentylenetetrazole injection induced generalized clonic seizures and 100% mortality. Sclareol pretreatment exhibited a prolonged latency to 1-3 stages of clonic convulsions with significant incidence reduction of lethality. Sclareol at both doses was not neurotoxic in rotarod test. In the hot-plate test, sclareol showed analgesic effect at 60 and 90 min after drug administration. Finally, in addition to its central anti-nociceptive effect, sclareol also protected against chemically- and electrically-induced seizures with no central nervous system side effects. Our findings suggest that sclareol could be a leading compound for a potential new antiepileptic and analgesic drug.

Antinociceptive and Antipruritic Effects of HSK21542, a Peripherally-Restricted Kappa Opioid Receptor Agonist, in Animal Models of Pain and Itch.

Kappa opioid receptor (KOR) agonists have been promising therapeutic candidates, owing to their potential for relieving pain and treating intractable pruritus. Although lacking morphine-like central nervous system (CNS) effects, KOR agonists do elicit sedation, dysphoria and diuresis which seriously impede their development. Peripherally-restricted KOR agonists have a poor ability to penetrate into the CNS system, so that CNS-related adverse effects can be ameliorated or even abolished. However, the only approved peripherally-restricted KOR agonist CR845 remains some frequent CNS adverse events. In the present study, we aim to address pharmacological profiles of HSK21542, with an expectation to provide a safe and effective alternative for patients who are suffering from pain and pruritus. The in vitro experimental results showed that HSK21542 was a selective and potent KOR agonist with higher potency than CR845, and had a brain/plasma concentration ratio of 0.001, indicating its peripheral selectivity. In animal models of pain, HSK21542 significantly inhibited acetic acid-, hindpaw incision- or chronic constriction injury-induced pain-related behaviors, and the efficacy was comparable to CR845 at 15 min post-dosing. HSK21542 had a long-lasting analgesic potency with a median effective dose of 1.48 mg/kg at 24 h post-drug in writhing test. Meanwhile, the antinociceptive activity of HSK21542 was effectively reversed by a KOR antagonist nor-binaltorphimine. In addition, HSK21542 had powerful antipruritic activities in compound 48/80-induced itch model. On the other hand, HSK21542 had a weak ability to produce central antinociceptive effects in a hot-plate test and fewer effects on the locomotor activity of mice. HSK21542 didn’t affect the respiratory rate of mice. Therefore, HSK21542 might be a safe and effective KOR agonist and promising candidate for treating pain and pruritus.

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.

The Role of Peripheral Opioid Receptors in the Development of Tolerance to Mu‐Opioid Receptor Agonists

Opioids are regarded as the most effective drugs for pain therapy. However, adverse effects, such as tolerance development, hinder the effectiveness of opioids during chronic treatment. Therefore, elucidating mechanisms involved in tolerance may aid in the design of novel treatments of chronic pain. This study evaluates the role of peripheral opioid receptors in tolerance development to mu-opioid receptor (MOR) agonists. All animals used in this study were male, C57BL/6N, and weighed between 20-30 g at 7-15 weeks old. Antinociceptive effects of MOR agonists were evaluated in a state of inflammatory pain (CFA-induced mechanical allodynia) and a centrally-mediated, thermal reflex assay (50°C warm water tail withdrawal (WWTW)). Following five days of 3x daily administration of morphine (10mg/kg), the ED50 of the morphine dose-effect curve was shifted 2.5-fold to the right in both assays. Interestingly, in the same two assays, naloxone-methiodide (10mg/kg) pretreatments before each chronic morphine injection prevented the rightward shift in the morphine dose-effect curve without altering the acute antinociceptive effects of morphine in mice treated with chronic saline. In the WWTW, five days of 4x daily administration of loperamide (3.2mg/kg, an ineffective dose in the WWTW) was sufficient to produce cross-tolerance to the antinociceptive effects of morphine, as displayed by a rightward shift in the morphine dose-effect curve. Pretreatments of naloxone-methiodide (10mg/kg) completely attenuated loperamide-induced cross-tolerance to the antinociceptive effects of morphine. These results suggest that repeated activation of peripheral opioid receptors may be involved in developing tolerance to the central antinociceptive effects of MOR agonists.

Effects of intrathecal and intracerebroventricular microinjection of kaempferol on pain: possible mechanisms of action.

Background and purpose:Kaempferol (KM), a flavonoid, has an anti-inflammatory and anticancer effect and prevents many metabolic diseases. Nonetheless, very few studies have been done on the antinociceptive effects of KM. This research aimed at assessing the involvement of opioids, gamma-aminobutyric acid (GABA) receptors, and inflammatory mediators in the antinociceptive effects of KM in male Wistar rats.Experimental approach:The intracerebroventricular and/or intrathecal administration of the compounds was done for examining their central impacts on the thermal and chemical pain by the tail-flick and formalin paw tests. For assessing the role of opioid and GABA receptors in the possible antinociceptive effects of KM, several antagonists were used. Also, a rotarod test was carried out for assessing motor performance.Findings/Results:The intracerebroventricular and/or intrathecal microinjections of KM (40 μg/rat) had partially antinociceptive effects in the tail-flick test in rats (P < 0.05). In the formalin paw model, the intrathecal microinjection of KM had antinociceptive effects in phase 1 (20 and 40 μg/rat; P < 0.05 and P < 0.01, respectively) and phase 2 (20 and 40 μg/rat; P < 0.01 and P < 0.001, respectively). Using naloxonazine and/or bicuculline approved the involvement of opioid and GABA receptors in the central antinociceptive effects of KM, respectively. Moreover, KM reduced the expression levels of caspase 6, interleukin-1β, tumor necrosis factor-α, and interleukin-6. The antinociceptive effects of KM were not linked to variations in the locomotor activity.Conclusion and implications:It can be concluded that KM has remarkable antinociceptive effects at a spinal level, which is associated with the presence of the inflammatory state. These impacts were undetectable following injections in the lateral ventricle. The possible mechanisms of KM antinociception are possibly linked to various modulatory pathways, including opioid and GABA receptors.

The In Vivo Antinociceptive and Antiinflammatory Effects of Verbascum exuberans Hub.-Mor.

Safe and effective drugs are still lacking for many pain therapies. In recent years, growing interest has been devoted thus on herbal drugs as an option to identify new pain killers. Based on this, extensive researches are carried out on Verbascum L. genus due to its therapeutic potency on pain and inflammation therapy. In this study, among Verbascum species, the antinociceptive effect of Verbascum exuberans Hub.-Mor., and its contributions to nitrergic, serotonergic, or opioidergic pathways as well as its antiinflammatory acitivity were investigated. Tail clip, tail flick, and hot plate tests were used to determine the central (spinal and supraspinal) antinociceptive effect, while an acetic acid-induced writhing test was used to measure the peripheral antinociceptive effect of the extract (250 and 500 mg/kg). The extract (250 mg/kg) was then combined with nω-nitro-L-arginine methyl ester, cyproheptadine, and naloxone to evaluate its involvement in nitrergic, serotonergic, or opioidergic pathways, respectively. Carrageenan-induced hind paw edema model was used to determine the antiinflammatory effect of the extract (250 mg/kg). The extract shows central spinal but not central supraspinal antinociceptive effect, and presents peripheral antinociceptive effect. The antinociceptive actions of the extract is largely regulated via targeting the nitrergic pathway, while the opioidergic pathway is partly involved. Further, the extract shows antiinflammatory effect due to the significant inhibitions on the time dependent edema progression and the cytokine (tumor necrosis factor-alfa and interleukin-1beta) productions. V. exuberans could be stated as a new source with a high beneficial potential in alleviating pain and inflammation.

Aristolochia trilobata: Identification of the Anti-Inflammatory and Antinociceptive Effects

Aristolochia trilobata, popularly known as “mil-homens,” is widely used for treatment of stomach aches, colic, asthma, pulmonary diseases, diabetes, and skin affection. We evaluated the antinociceptive and anti-inflammatory activities of the essential oil (EO) and the main constituent, 6-methyl-5-hepten-2-yl acetate (sulcatyl acetate, SA). EO and SA (1, 10, and 100 mg/kg, p.o.) were evaluated using chemical (formalin-induced licking) and thermal (hot-plate) models of nociception or inflammation (carrageenan-induced cell migration into the subcutaneous air pouch, SAP). The mechanism of antinociceptive activity was evaluated using opioid, cholinergic receptor antagonists (naloxone and atropine), or nitric oxide synthase inhibitor (L-NAME). EO and SA presented a central antinociceptive effect (the hot-plate model). In formalin-induced licking response, higher doses of EO and SA also reduced 1st and 2nd phases. None of the antagonists and enzyme inhibitor reversed antinociceptive effects. EO and SA reduced the leukocyte migration into the SAP, and the cytokines tumor necrosis factor and interleukin-1 (TNF-α and IL-1β, respectively) produced in the exudate. Our results are indicative that EO and SA present peripheral and central antinociceptive and anti-inflammatory effects.

Pharmacological evaluation underlying the antinociceptive activity of two new hybrids NSAIDs tetrahydropyran derivatives.

The development of analgesic drugs is still a necessity due to the inefficiency of the current treatments for some pathological conditions and also due to the adverse effects produced by these drugs. The aim of this study was to deepen the pharmacological study of two new hybrids NSAIDs tetrahydropyran derivatives, regarding their antinociceptive effects on acute pain in mice. Male swiss mice were evaluated in the acetic acid-induced abdominal writhing, formalin, tail-flick, open-field, glutamate- and capsaicin-induced paw licking tests, and in vitro Cox inhibition assay, besides the acute toxicological evaluation. The compounds had an effect on the acetic acid-induced abdominal writhing, formalin (both phases), and tail-flick tests. In the study of the mechanism of action was observed reversion of the antinociceptive effect of the compounds from the previous administration of naloxone, L-NAME (L-nitro-arginine methyl ester), ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), glibenclamide, and nor-binaltorphimine, by the intrathecal and intraperitoneal routes. The prior administration of MK-801 suggests that the modulation of NMDA receptor contributes to the antinociceptive effect of compounds. In summary, hybrid compounds presented central antinociceptive effect, demonstrating participation of the NO-cGMP-K+ ATP pathway, κ-opioid, and NMDA receptors. In addition, the compounds showed inhibition of cyclo-oxygenase enzymes and adverse effects were not observed with dose 300 times greater than the dose used experimentally.

Anti-inflammatory and central and peripheral anti-nociceptive activities of α-asarone through the inhibition of TNF-α production, leukocyte recruitment and iNOS expression, and participation of the adenosinergic and opioidergic systems.

Alpha-asarone has been found to possess many pharmacological activities, which can improve cognitive function and exert anti-oxidant, anxiolytic, anti-epileptic and protective effects against endothelial cell injury. The anti-inflammatory activity of α-asarone was evaluated using lipopolysaccharide (LPS)-induced paw oedema. Moreover, leukocyte migration, inducible nitric oxide synthase (iNOS) expression and tumour necrosis factor-alpha (TNF-α) levels were quantified in footpads. Formalin and LPS-induced thermal hyperalgesia models were generated using adenosinergic, opioidergic, serotonergic and muscarinic receptor antagonists. The effects on motor coordination were evaluated by means of the rota-rod test. Oral treatment (p.o.) with α-asarone (3mg/kg) significantly inhibited paw oedema by 62.12 and 72.22%, 2 and 4h post LPS injection, respectively. Alpha-asarone (3mg/kg, p.o.) attenuated the inflammatory infiltrate 1, 3 and 6h after LPS injection. Furthermore, α-asarone (3mg/kg, p.o.) suppressed iNOS expression and TNF-α production, 6 and 1h after inflammatory stimulus, respectively. Alpha-asarone (3, 10 and 30mg/kg, p.o.) inhibited both phases of formalin-induced licking. In the hot-plate test, α-asarone (10 and 30mg/kg, p.o.) increased the latency to response 3 and 5h post LPS stimulus. Caffeine and naloxone abolished the central anti-nociceptive effect of α-asarone (neurogenic phase of formalin and hot plate tests), suggesting the participation of the adenosinergic and opioidergic systems. Furthermore, naloxone reversed the peripheral activity of α-asarone (inflammatory phase of formalin test), indicating the possible involvement of the opioidergic pathway. In the rota-rod test, α-asarone did not change motor coordination. These findings suggest that α-asarone has anti-inflammatory, peripheral and central anti-nociceptive effects and could represent a promising agent for future research.

Antinociceptive and genotoxic assessments of the antagonist TRPV1 receptor SB-366791 on morphine-induced tolerance in mice.

Chronic pain is mainly treated with opioid analgesics such as morphine. However, the use of these substances can cause adverse effects, including dependence and tolerance, necessitating the discovery of a new approach to analgesic therapies. The transient receptor potential vanilloid 1 (TRPV1) is linked to thermal sensibility and has been considered as a new therapeutic option for pain treatment. This study aims to investigate the antinociceptive effect and toxicity of SB-366791, a TRPV1 antagonist. Morphine-tolerant and morphine non-tolerant Swiss mice were submitted to the hot plate and thermal tail flick tests. Toxicological evaluations of the genotoxic and mutagenic activities of SB-366791 were assessed using a comet assay and micronucleus test, and the Salmonella/microsome mutagenicity assay. In the hot plate test, intrathecal injection of SB-366791 or morphine resulted in significantly increased antinociception in non-tolerant mice. SB-366791 also led to an analgesic effect in the tail flick test. Tolerant mice that received SB-366791 demonstrated a central antinociceptive effect in both thermal tests. No genotoxic effects were observed in the comet assay and no mutagenic effects were detected in the micronucleus test or in the Salmonella/microsome assay. Behavioral results of the thermal nociception tests show that SB-366791 has antinociceptive potential in both morphine-tolerant and non-tolerant mice and does not cause genotoxic or mutagenic effects. Nevertheless, new studies should be performed to clarify the activity and participation of vanilloid channels in the antinociception of SB-366791.

Anti-inflammatory, antinociceptive and antioxidant activities of the hydromethanolic fraction from Annona nutans leaves

Annona nutans (Annonaceae) is a plant species found in Bolivia, Paraguay, Argentina, and the Brazilian Cerrado, specifically in the states of Mato Grosso and Mato Grosso do Sul (Brazil). Its common names are Araticû-Mi and Araticû-Ñu. The research contributions regarding the chemical composition and biological activities of extracts from A. nutans are rare, with only four articles being found in the literature. Therefore, the present study evaluated the anti-inflammatory and antinociceptive activities of the hydromethanolic fraction (FHMeOH) using carrageenan-induced paw edema and hot-plate tests. In addition, the antioxidant activity was evaluated by DPPH radical scavenging, total phenolic, flavonoid and tannin content assays and quantification of the major metabolites by LC-MS were performed. Oral treatment with the FHMeOH (at a dose of 300 mg.kg-1) significantly reduced paw edema 2 h and 4 h after the inflammatory stimulus. The intraperitoneal (i.p.) treatment with the FHMeOH (50 and 100 mg.kg-1) proved to be most effective, and the inhibition of acute inflammation was still visible 6 h after carrageenan injection. At doses of 50 and 100 mg.kg-1 (i.p.), FHMeOH exhibits central antinociceptive effects by increasing the latency of the reaction in the hot-plate model. The FHMeOH showed antioxidant potential, and the metabolites quercetin-3-O-galactoside, quercetin-3-O-glucoside, isorhamnetin-3-O-galactoside, quercetin-3-O-β-D-apiofuranosyl-(1→2)-galactopyranoside, and chlorogenic acid were identified and quantified by LC-MS. Our results indicate, for the first time, that FHMeOH has anti-inflammatory, antinociceptive and antioxidant potential, and it is a promising source of studies for new herbal medicines

Antinociceptive activities of Artocarpus lacucha Buch-ham (Moraceae) and its isolated phenolic compound, catechin, in mice

BackgroundThe present study evaluated the antinociceptive effect of the bark of Artocarpus lacucha, which is used for the treatment of stomachache, headache and boils in the traditional system of medicine.MethodsThe antinociceptive activity was investigated by the tail immersion, hot plate, acetic acid- & formalin-induced nociception and carrageenan-induced paw edema tests using a hydro-methanolic extract of A. lacucha bark. The plant extract was found to contain a substantial amount of phenolic compounds according to the total phenolic and flavonoid content assay. A phenolic metabolite, (+)-catechin, has been isolated using different chromatographic techniques. The compound was characterized with 1D and 2D NMR spectroscopic data. (+)-catechin, isolated from A. lacucha was assessed for antinociceptive effects swiss albino mice. Furthermore, the possible involvement of opioid receptors and ATP-sensitive K+ channel for the effect of the plant extract and (+)-catechin has been justified using naloxone and glibenclamide, respectively.ResultsOral administration (p.o) of the plant extract (50–200 mg/Kg b.w.) resulted in significant thermal pain protection in the hot plate and tail immersion tests. The action of the plant extract was significantly antagonized by naloxone, a non-selective opioid antagonist, in the hot plate and tail immersion tests, which supports the involvement of opioid receptors. Both the plant extract and (+)-catechin, (50–200 mg/Kg b.w., p.o.) significantly diminished the acetic acid- & formalin-induced nociception, and carrageenan-induced paw edema. Glibenclamide, an ATP-sensitive K+ channel blocker, significantly reversed their effect in the acetic acid-induced writhing test which indicates the participation of ATP-sensitive K+ channel system.ConclusionsThe investigation revealed potential central and peripheral antinociceptive effects of A. lacucha bark supports its applications in the traditional system of medicine.

Antinociceptive and Anxiolytic-Like Effects of Some Compounds Carrying Benzothiazole Ring

The aim of this study was to examine the antinociceptive and anxiolytic-like effects of some compounds carrying benzothiazole ring. The antinociceptive effects of test compounds, administrated at a dose of 40 mg/kg, were investigated by tail clip, hot plate and acetic acid-induced writhing tests. Hole board and elevated plus maze tests were performed to evaluate the anxiolytic-like effects of the compounds. Rota-rod device was used to assess the motor coordinations of mice. As a result of the experiments, it was determined that compounds 3f, 3g and 3h increased the reaction times of animals in the tail clip and hot plate tests, and compound 3e reduced the writhing number of mice in the acetic acid-induced writhing test. On the other hand, in the hole board test, compounds 3f, 3g and 3h reduced the first head-dipping latencies of mice while increasing the total number of head-dips. In the elevated plus maze test, it has been shown that the same derivatives increase the percentages of open arm entries and time spent in the open arms. In the Rota-rod tests, test compounds did not change the falling time of mice from the rotating mill. All these findings point out that compounds 3f, 3g and 3h exhibit central antinociceptive and anxiolytic-like effects and compound 3e shows a peripheral antinociceptive effect.

Analgesic and antiinflammatory activities of the essential oil from Artemisia sieberi Besser

The analgesic activity of Artemisia sieberi oil was assessed by acetic acid-induced writhing test and Eddy’s hot plate method; while the acute anti-inflammatory effect was investigated by inflammatory paw edema test in rats. The administration rout of the essential oil, standard drugs and the vehicle used in all assays was intraperitoneal injection. The 1 and 2.5 mg/kg doses of the studied oil significantly decreased the number of acetic acid-induced writhes in mice. The dose of 1 mg/kg of the oil also exhibited a central analgesic effect as evidenced by a significant increase in reaction time at several time points after 15 min treatment in the hot plate method. In addition, the 1 mg/kg dose of the oil significantly reduced carrageenan induced paw edema in rats at the first hour of the test by 72.7% inhibition and lasted to the third hour of the test by 74.3% inhibition found to be very close to that of the standard drug, diclofenac sodium (50 mg/kg). The major components of the oil were characterized as camphor (31.2%) and 1,8-cineole (20.0%). The results suggest that A. sieberi essential oil has a significant effect against acute inflammation and has central and peripheral anti-nociceptive effects.

New \u03b2N-octadecanoyl-5-hydroxytryptamide: antinociceptive effect and possible mechanism of action in mice

The present study examined the potential antinociceptive activity of C18 5-HT (βN-octadecanoyl-5-hydroxytryptamide) using chemical and thermal nociception models in mice. Orally administered C18 5-HT (0.1, 1 and 10 mg/kg) produced significant dose-dependent antinociceptive effects in formalin-, capsaicin- and glutamate-induced licking models. This compound also induced a significant increase in the response to thermal stimuli in the hot plate test, and its antinociceptive effect was not related to muscle relaxant or sedative actions. In a thermal hyperalgesia model, C18 5-HT presented an anti-hyperalgesic profile as evidenced by the increase in the response time of the animals. Furthermore, intraperitoneal (i.p) pretreatment with naloxone (a non-selective opioid receptor antagonist, 1 mg/kg), ondansetron (serotoninergic receptor antagonist (5-HT3 subtype), 0.5 mg/kg) or AM241 (CB1 cannabinoid receptor antagonist, 1 mg/kg) reversed the antinociceptive effects of C18 5-HT in the hot plate model. In the formalin-induced licking model, pretreatment with naloxone reversed the antinociceptive effects of C18 5-HT, as demonstrated by an increase in the paw licking response when compared with the C18 5-HT-treated group. These findings suggest that C18 5-HT has peripheral and central antinociceptive effects and that its mechanism of action involves, ate least in part, opioid, serotoninergic and cannabinoid pathways.