Late Phase Of Formalin-induced Licking Research Articles

Phytochemical and pharmacological evaluation of methanolic extract of Lathyrus sativus L. seeds

BackgroundLathyrus sativus L. (Fabaceae) has long been used as a traditional medicine for the treatment of several ailments such as Scabies, eczema, and allergy. The aim of the study was to evaluate the phytochemical nature with Central Nervous System (CNS) depressant, analgesic, antipyretic activities of the methanolic plant extract of Lathyrus sativus L. seeds in different experimental models.MethodsPreliminary phytochemical screening and proximate analysis was carried out using different standard methods. CNS depressant activity was evaluated observing the effects of plant extract on Swiss albino mice using open field and hole-cross method. Acetic acid induced writhing and formalin induced paw licking methods were used for the appraisal of analgesic activity while 2,4-dinitrophenol (DNP) induced pyrexia model was used to investigate the antipyretic activity. The data were analyzed by one way ANOVA followed by Dunnett’s test using SPSS (version 20).ResultsThe phytochemical analysis revealed the presence of wide range of phytoconstituents in the plant extract. Our investigation demonstrated that the methanolic plant extract significantly (p < 0.001) decreased the locomotor activity of mice in open field and hole-cross method at both the tested doses (200 and 300 mg/kg) which were comparable to the standard drug diazepam (1 mg/kg). The plant extracts significantly (p < 0.001) inhibited the writhing induced by acetic acid in mice to 87.09% and 80.65% (200 and 300 mg/kg respectively) compared to the standard indomethacin (70.97%). The extracts (200 and 300 mg/kg respectively) also significantly (p < 0.001) reduced the writhing to 43.39%, 64.15% in early and 46.15%, 97.44% in late phase of formalin-induced licking and biting. In 2,4-DNP induced pyrexia the extracts exhibited protection at 200 and 400 mg/kg, similar to standard drug aspirin at 150 mg/kg.ConclusionThe results demonstrated that the plant extract has potential CNS depressant, analgesic and antipyretic activity.

Screening of Baccaurea ramiflora (Lour.) extracts for cytotoxic, analgesic, anti-inflammatory, neuropharmacological and antidiarrheal activities

BackgroundIt has been observed that the various part of Baccaurea ramiflora plant is used in rheumatoid arthritis, cellulitis, abscesses, constipation and injuries. This plant also has anticholinergic, hypolipidemic, hypoglycemic, antiviral, antioxidant, diuretic and cytotoxic activities. The present studyaimed to assess the cytotoxic, analgesic, anti-inflammatory, CNS depressant and antidiarrheal activities of methanol extract of Baccaurea ramiflora pulp and seeds in mice model.MethodsThe cytotoxic activity was determined by brine shrimp lethality bioassay; anti-nociceptive activity was determined by acetic acid-induced writhing, formalin- induced licking and biting, and tail immersion methods. The anti-inflammatory, CNS depressant and anti-diarrheal activities were assessed by carrageenan-induced hind paw edema, the open field and hole cross tests, and castor oil-induced diarrheal methods, respectively. The data were analyzed by one way ANOVA (analysis of variance) followed by Dunnett’s test.ResultsIn brine shrimp lethality bioassay, the LC50 values of the methanol extracts of Baccaurea ramiflora pulp and seed were 40 μg/mL and 10 μg/mL, respectively. Our investigation showed that Baccaurea ramiflora pulp and seed extracts (200 mg/kg) inhibited acetic acid induced pain 67.51 and 66.08%, respectively (p < 0.05) that was strongly comparable with that of Ibuprofen (72%) (p < 0.05). The Baccaurea ramiflora pulp and seed extracts (200 mg/kg) significantly (p < 0.05) reduced 58.5 and 53.4 in early and 80.8%, 76.61% in late phase of formalin-induced licking and biting. At 60 and 90 min pulp and seed extracts (200 mg/kg) inhibited nociception of thermal stimulus 50.16 and 62.4%, respectively (p < 0.05) which was comparable with the standard (morphine, 75.9% inhibition). The pulp and seed extracts (200 mg/kg) significantly (p < 0.05) reduced inflammation (42.00 and 55.22%, respectively) in carrageenan-induced hind paw edema and defecations (59.7 and 63.03%, respectively) in castor oil induced diarrhea. Both the extracts showed high sedative activity at 30, 60, 90, and 120 min.ConclusionOur investigation demonstrated significant cytotoxic, analgesic, anti-inflammatory, CNS depressant and antidiarrheal activities of methanol extract of Baccaurea ramiflora pulp and seeds (200 mg/kg).

Inosine Reduces Pain-Related Behavior in Mice: Involvement of Adenosine A1 and A2A Receptor Subtypes and Protein Kinase C Pathways

Inosine, an endogenous purine, is the first metabolite of adenosine in a reaction catalyzed by adenosine deaminase. This study aimed to investigate the antinociceptive effects of inosine against several models of pain in mice and rats. In mice, inosine given by systemic or central routes inhibited acetic acid-induced nociception. Furthermore, inosine also decreased the late phase of formalin-induced licking and the nociception induced by glutamate. Inosine produced inhibition (for up to 4 h) of mechanical allodynia induced by complete Freund's adjuvant (CFA) injected into the mouse's paw. Given chronically for 21 days, inosine reversed the mechanical allodynia caused by CFA. Moreover, inosine also reduced the thermal (cold stimuli) and mechanical allodynia caused by partial sciatic nerve ligation (PSNL) for 4 h; when inosine was chronically administered, it decreased the mechanical allodynia induced by PSNL for 22 days. Antinociception caused by inosine in the acetic acid test was attenuated by treatment of mice with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; a selective adenosine A(1) receptor antagonist), 8-phenyltheophylline (8-PT; a nonselective adenosine A(1) receptor antagonist), and 4-{2- [7-amino-2-(2-furyl)[1,2,4]triazolo-[2,3-a][1,3,5]triazin-5-yl- amino]ethyl}phenol (ZM241385; a selective adenosine A(2A) receptor antagonist). In rats, inosine inhibited the mechanical and heat hyperalgesia induced by bradykinin and phorbol 12-myristate 13-acetate, without affecting similar responses caused by prostaglandin E(2) or forskolin. These results indicate that inosine induces antinociceptive, antiallodynic, and antihyperalgesic effects in rodents. The precise mechanisms through which inosine produces antinociception are currently under investigation, but involvement of adenosine A(1) and A(2A) receptors and blockade of the protein kinase C pathway seem to largely account for inosine's antinociceptive effect.

Spinal and supraspinal antinociceptive action of dipyrone in formalin, capsaicin and glutamate tests. Study of the mechanism of action

Dipyrone injected intraperitoneally (i.p.) or subplantarly into the mouse paw caused dose-related antinociception against the early and the late phases of formalin-induced licking, with mean ID 50 values of 154.5 and 263.7 μmol/kg, and 2.6 and 1.2 μmol/paw, respectively. Given either by intracerebroventricular (i.c.v.) or by intrathecal (i.t.) routes, dipyrone produced a similar inhibition of both phases of the formalin-induced licking, with mean ID 50 values of 0.4 and 1.3 μmol/site, and 0.4 and 0.9 μmol/site against the early and the late phase of the formalin response, respectively. Dipyrone, given by i.p., subplantar, i.t. or i.c.v. routes, caused dose-related antinociception of capsaicin-induced licking. The mean ID 50 values were: 207.6 μmol/kg, 2.2 μmol/paw, 0.4 μmol/site and 0.14 μmol/site, respectively. In addition, dipyrone given i.p. caused a significant increase of the latency both in the hot-plate and the tail-flick assays. Dipyrone, given i.p., i.t. or i.c.v., reversed significantly the hyperalgesia caused by i.t. injection of glutamate, with mean ID 50 values of 9 μmol/kg, 29 nmol/site and 94 nmol/site, respectively. The antinociception caused by dipyrone was not influenced by naloxone, l-arginine, phaclofen, glibenclamide, p-chlorophenylalanine methyl ester, pertussis toxin or by adrenal gland hormones, when assessed against the formalin assay. Dipyrone analgesic action was not secondary to its anti-inflammatory effect, nor was it associated with non-specific effects such as muscle relaxation or sedation actions of animals. Dipyrone at a higher concentration caused significant inhibition of [ 3H]glutamate binding (37%) in cerebral cortical membranes from both mice and rats. However, dipyrone had no significant effect on brain constitutive neuronal nitric oxide synthase activity. It is concluded that dipyrone produces peripheral, spinal and supraspinal antinociception when assessed on formalin and capsaicin-induced pain as well as in glutamate-induced hyperalgesia in mice. Dipyrone antinociception seems unlikely to involve an interaction with the l-arginine-nitric oxide pathway, serotonin system, activation of G i protein sensitive to pertussis toxin, interaction of ATP-sensitive K + channels, GABA B receptors, or the release of endogenous glucocorticoids. However, a modulatory effect on glutamate-induced hyperalgesia and, to a lesser extent, an interaction with glutamate binding sites, seems to account for its analgesic action.

Antinociceptive properties of the hydroalcoholic extract and preliminary study of a xanthone isolated from Polygala cyparissias (Polygalaceae)

Polygala cyparissias (Polygalaceae) grows abundantly on Brazil's Atlantic coast, belonging to the typical underbrush vegetation of dunes and have been used in folk medicine for treatment of several diseases, such as disturbances of bowel and kidney. The hydroalcoholic extract of P. cyparissias (HE, 3 to 60 mg kg −1, i.p. or 25 to 200 mg kg −1, p.o.) produced significant and graded inhibition of acetic acid-induced abdominal constrictions, with mean ID 50 values of 6 and 72 mg kg −1, respectively. The HE (at this same range of doses) also produced dose-related inhibition of both the early and the late phase of formalin-induced licking. The calculated mean ID 50 values for the early phase were: > 60 and > 200 mg kg −1, while for the late phase they were 11 and 101 mg kg −1, respectively, by i.p. and p.o. routes. The HE also caused dose-related inhibition of formalin-induced edema formation (P < 0.01). The HE (3 to 60 mg kg −1, i.p. or 50 to 200 mg kg −1, p.o.) produced significant and dose-related inhibition of the neurogenic nociception caused by topical injection of capsaicin, with mean ID 50 values of 12 and 71 mg kg −1, respectively. Given orally, the HE (50 to 200 mg kg −1) prevented in a dose-dependent manner, bradykinin (3 nmol paw ) and substance P (10 nmol paw )-induced hyperalgesia in the rat paw, with mean ED 50 values of 122 and 121 mg kg −1, respectively, but was ineffective in the hot-plate model of nociception. The antinociception caused by the HE, in contrast to that of morphine (5 mg kg −1, s.c.), was not reversed by naloxone (5 mg kg −1, i.p.) when assessed in the acetic acid writhing test. The HE, at antinociceptive doses, did not affect motor coordination of animals when assessed in the rota-rod model. The xanthone isolated from P. cyparissias, identified as 1,7-dihydroxy-2,3-dimethoxy xanthone (0.3 to 30 mg kg −1, i.p.), produced dose-related inhibition of acetic acid-induced abdominal constriction, with mean ID 50 value of 1.5 mg kg −1. These data show that the active principle(s) present in the HE of P. cyparissias, elicited pronounced antinociception when assessed by i.p or p.o. routes, against both inflammatory and neurogenic nociception, and was able to prevent bradykinin and substance P-induced hyperalgesia. Its precise mechanism of action still remains unclear.