Formalin-induced Licking Models Research Articles

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.

Anti-inflammatory, antinociceptive and antioxidant properties of Schinopsis brasiliensis bark

Ethnopharmacological relevanceSchinopsis brasiliensis is a native plant from Brazil, popularly used in folk medicine to relieve pain and treat inflammation. This study evaluated the antinociceptive and anti-inflammatory activities and antioxidant properties of the hydroethanol extract (HEE) and ethyl acetate fraction (EAF) obtained from S. brasiliensis bark. Materials and methodsThe HEE and EAF of S. brasiliensis bark (10, 30 and 100mg/kg, p.o.) were evaluated using models of analgaesia (formalin-induced licking and hot-plate models) or inflammation (licking response by formalin-induced and carrageenan-induced cell migration into the subcutaneous air pouch). The antioxidant activities of HEE and EAF (50, 100 and 200µg/ml) were evaluated using the lipoperoxidation method induced in egg yolk by 2′-azobis(2-amidinopropane) dihydrochloride (AAPH) and FeSO4. ResultsHEE and EAF presented a central antinociceptive effect (at 100mg/kg dose), increasing the baseline and area under the curve in the hot plate model. EAF (100mg/kg) significantly reduced (p< 0.005) the pain response in the first (45%) and second (35%) phases of the formalin-induced licking model, while HEE (100mg/kg) reduced (38%) only the pain response in the second phase. Regarding anti-inflammatory activity, EAF (100mg/kg) also inhibited the inflammatory process induced by subcutaneous carrageenan injection in the SAP model, reducing the amount of the cytokine TNF-α produced. ConclusionHEE and EAF from S. brasiliensis bark show pharmacological interest because they were able to inhibit the peripheral and central transmission of pain. Our data also suggest that the anti-inflammatory activity caused by EAF exposure occurs through the inhibition of the pro-inflammatory cytokine TNF-α, also reducing the spreading of the inflammatory processes by neutralizing reactive oxygen species, which are by-products in the biosynthesis of pain mediators.

English

&nbsp; This study investigated the analgesic and anti-inflammatory effects of&nbsp;Crinum asiaticum&nbsp;(Amaryllidaceae)&nbsp;leaf ethanolic extract.&nbsp;Analgesic effect&nbsp;was&nbsp;investigated in acetic acid induced writhing model and formalin induced licking model in&nbsp;swiss albino mice. Anti-inflammatory effect&nbsp;was&nbsp;conducted in&nbsp;carrageenan-induced&nbsp;paw edema model of&nbsp;albino&nbsp;rat.&nbsp;Data were analyzed by one-way analysis of variance (ANOVA) followed by&nbsp;post hoc&nbsp;multiple comparison test.&nbsp;In analgesic study,&nbsp;C.&nbsp;asiaticumextract inhibited 42.34&plusmn;3.20% of acetic acid induced pain at higher dose&nbsp;of&nbsp;2.0 g/kg body weight.&nbsp;The effect was statistically significant (p&lt;0.001) compared to&nbsp;the&nbsp;positive control, diclofenac sodium (10 mg/kg).&nbsp;The extract reduced the formalin induced pain22.60&plusmn;1.39% in early phase and 27.11&plusmn;0.87% in late phase&nbsp;at the same dose&nbsp;of&nbsp;2.0 g/kg and the reductions were significant (p&lt;0.01) compared to&nbsp;the&nbsp;positive control morphine (0.5 mg/kg). In&nbsp;a time-dependent inhibition of carrageenan-induced paw edema model, the extract promoted the inhibitions of paw edema 51.60&plusmn;2.50% at the 1st&nbsp;h and 40.80&plusmn;0.52% at the 4th&nbsp;h of administration. These inhibitions were also significant (p&lt;0.01) in comparison to those promoted by diclofenac sodium. No mortality was observed in acute toxicity test. The study concludes that&nbsp;C. asiaticumleaf extract has potential analgesic and anti-inflammatory effects to be recorded as plant-derived complementary medicine. &nbsp; Key&nbsp;words:&nbsp;Crinum asiaticum,&nbsp;anti-inflammatory,&nbsp;analgesic, Carrageenan,&nbsp;formalin.

Convolutamydine A and synthetic analogues have antinociceptive properties in mice

Convolutamydine A, an oxindole that originated from a marine bryozoan, has several biological effects. In this study, we aimed to investigate the antinociceptive effects of convolutamydine A and two new synthetic analogues.Convolutamydine A and the two analogues were given orally to assess their ability to induce antinociceptive effects. Formalin-induced licking response, acetic acid-induced contortions, and hot plate models were used to characterize the effects of convolutamydine A and its analogues.Convolutamydine A (4,6-bromo-3-(2-oxopropyl)-3-hydroxy-2-oxindole), compound 1 (3-(2-oxopropyl)-3-hydroxy-2-oxindole), and compound 2 (5-bromo-3-(2-oxopropyl)-3-hydroxy-2-oxindole) caused peripheral antinociceptive and anti-inflammatory effects in the acetic acid-induced contortions and the formalin-induced licking models. Supraspinal effects were also observed in the hot plate model and were similar to those obtained with morphine. The peripheral effects were not mediated by the cholinergic or opioid systems. The antinociceptive effects of convolutamydine A seem to be mediated by all three systems (cholinergic, opioid, and nitric oxide systems), and the mechanism of action of compounds 1 and 2 involved cholinergic and nitric oxide-mediated mechanisms. Convolutamydine A and its analogues (compounds 1 and 2) showed good antinociceptive ability after systemic administration in acute pain models. The antinociceptive action mediated by cholinergic, opioid, and nitric oxide systems could explain why convolutamydine A, compound 1, and compound 2 retained their antinociceptive effects. The doses used were similar to the doses of morphine and were much lower than that of acetylsalicylic acid, the classical analgesic and anti-inflammatory drug.In conclusion, convolutamydine A and the two analogues demonstrated antinociceptive effects comparable to morphine's effects.

Analgesic and anti-inflammatory effect of whole Ageratum conyzoides and Emilia sonchifolia alcoholic extracts in animal models

This study was designed to investigate the analgesic and anti-inflammatory effects ofAgeratum conyzoides and Emilia sonchifolia alcoholic extracts in animal models. Analgesic effects have been investigated in acetic acid induced writhing model and formalin induced licking model of Swiss albino mice. Anti-inflammatory effect was investigated in carrageenan induced anti-inflammatory paw edema model of Wistar albino rat. Data were analyzed by one-way analysis of variance (ANOVA), followed by Tukey's post hoc test for multiple comparisons. In a dose-dependent response, A. conyzoides and E. sonchifolia extracts inhibited 49.85 and 39.47% of acetic acid induced pain at the highest dose 2.0 g/kg body weight (BW). These effects were statistically significant (P < 0.05) as compared to the reference drug, diclofenac sodium (40 mg/kg). A. conyzoides reduced 35.48% and E. sonchifolia reduced 38.70% of formalin induced pain by 2.0 g/kg which were also statistically significant (P < 0.05) as compared to morphine (0.5 mg/kg). In a time-dependent inhibition of carrageenan induced paw edema model, the extracts of A. conyzoides and E. sonchifoliapromoted 50.23 and 48.11% inhibition of paw edema at the 4th hour of administration, respectively and the effects were statistically significant (P < 0.05). No mortality was observed in acute toxicity test. Observed results demonstrate an effective analgesic and anti-inflammatory potentials of the extracts to be used as complementary and alternative therapy. Key words: Ageratum, Emilia, anti-inflammatory, analgesic, carrageenan.

Characterisation of the anti-inflammatory and antinociceptive activities and the mechanism of the action of Lippia gracilis essential oil

The species Lippia gracilis Schauer, known in Brazil as "Alecrim-da-chapada", is popularly used in folk medicine to treat cough, bronchitis, nasal congestion, and headache. Lippia gracilis essential oil (EO; 10, 30, and 100mg/kg, p.o.) and the reference drugs morphine (5mg/kg, p.o.) and acetylsalicylic acid (ASA; 200mg/kg, p.o.) were evaluated using models for analgesia (acetic acid-induced contortion, formalin-induced licking, and hot plate) or inflammation (formalin-induced licking response and subcutaneous air pouch model). To elucidate the antinociceptive mechanism of action, animals were pre-treated with naloxone (opioid receptor antagonist; 1mg/kg, i.p.), atropine (cholinergic antagonist; 1mg/kg, i.p.) or l-nitro arginine methyl ester (L-NAME; 3mg/kg, i.p.) 30 min prior to oral administration of EO. EO significantly inhibited the number of writhings in acetic acid-induced contortions and the time that the animal spent licking the formalin-injected paw (second phase). All doses of EO increased the baseline and the area under the curve in the hot plate model. The administration of naloxone did not reverse the antinociceptive effect of EO in the acetic acid-induced contortion and formalin-induced licking models. L-NAME and atropine significantly reversed the effect of EO in the models of contortion, formalin, and hot plate. EO also inhibited the inflammatory process induced by subcutaneous carrageenan injection, reducing cell migration, exudate volume, extravased protein, and inflammatory mediators (nitric oxide, prostaglandin E2, TNF-α, and IFN-γ) produced in the pouch. Our results indicate that the essential oil from Lippia gracilis produces an antinociceptive effect that could be potentially mediated by cholinergic receptors and the nitric oxide pathway. Our data also suggest that the anti-inflammatory activity caused by EO exposure occurs through inhibition of nitric oxide and PGE2 production.