Anti-nociceptive effects of <Emphasis Type="Italic">Carpolobia lutea</Emphasis> G. Don (Polygalaceae) leaf fractions in animal models

Leaves from Carpolobia lutea (Polygalaceae) were screened to establish the antiulcer ethnomedicinal claim and to quantitatively isolate, elucidate the active compounds by semi-preparative HPLC. The anti-nociceptive effects of Carpolobia lutea (CL) G. Don (Polygalaceae) organic leaf extracts were tested in experimental models in mice. The anti-nociceptive mechanism was determined using tail-flick test, acetic acid-induced abdominal constrictions, formalin-induced hind paw licking and the hot plate test. The fractions (ethanol, ethyl acetate, chloroform, n-hexane) and crude ethyl acetate extract of CL (770 mg/kg, i.p.) produced significant inhibitions of both phases of the formalin-induced pain in mice, a reduction in acetic acid-induced writhing as well as and an elevation of the pain threshold in the hot plate test in mice. The inhibitions were greater to those produced by indomethacin (5 mg/kg, i.p.). Ethyl acetate fraction revealed cinnamic and coumaric acids derivatives, which are described for the first time in literature. These cinnamalglucosides polyphenols characterised from CL may in part account for the pharmacological activities. These findings confirm its ethnomedical use in anti-inflammatory pain and in pains from gastric ulcer-associated symptoms.     

Antiinflammatory, Analgesic and Antipyretic Activities of Mimusops elengi Linn

In the present study, 70% ethanol extract of Mimusops elengi Linn. bark was assessed for antiinflammatory, analgesic and antipyretic activities in animals. The antiinflammatory activity of ethanol extract of Mimusops elengi (200 mg/kg, p.o) was evaluated using carrageenan-induced paw edema and cotton pellet-induced granuloma models. Analgesic effect was evaluated using acetic acid-induced writhing and Eddy's hot plate models and antipyretic activity was assessed by Brewer's yeast-induced pyrexia in rats. The ethanol extract of Mimusops elengi (200 mg/kg, p.o) significantly inhibited the carrageenan-induced paw oedema at 3rd and 4th h and in cotton pellet model it reduced the transudative weight and little extent of granuloma weight. In analgesic models the ethanol extract of Mimusops elengi decreases the acetic acid-induced writhing and it also reduces the rectal temperature in Brewer's yeast induced pyrexia. However, Mimusops elengi did not increase the latency time in the hot plate test. These results show that ethanol extract of Mimusops elengi has an antiinflammatory, analgesic and antipyretic activity.     

Anti-inflammatory studies on Adenanthera pavonina seed extract

A methanol extract of the seeds of Adenanthera pavonina was evaluated for pharmacological effects in animal models. The extract (50–200 mg/kg) produced statistically significant (P < 0.05) inhibition of the carrageenan-induced paw oedema in the rat, as well as the acetic-acid-induced vascular permeability in mice. At doses of 100 and 200 mg/kg, pleurisy induced with carrageenan was also inhibited. The extract (50–200 mg/kg) exhibited a dose-dependent and significant (P < 0.05) analgesic activity in the acetic-induced writhing in mice. In addition, both early and late phases of the formalin-induced paw licking in mice was inhibited by the extract. Acute toxicity studies revealed that the extract produced reduced motor activity. The LD₅₀ value of the extract was found to be 1.36 g/kg. This study demonstrated the anti-inflammatory and analgesic effects of A. pavonina extract.     

Antioxidant,antinociceptive and anti-inflammatory activities of atorvastatin and rosuvastatin in various experimental models

The present study was planned to investigate the antioxidant, antinociceptive, and anti-inflammatory activities of atorvastatin and rosuvastatin (1, 3 and 10 mg/kg, p.o.) in various animal models. The antinociceptive effect was assessed by chemically- (formalin, acetic acid) and thermally- (hot plate) induced nociception, while anti-inflammatory effect was evaluated using carrageenan-, formaldehyde-induced paw oedema and cotton pellet-induced granuloma. The effect of atorvastatin and rosuvastatin on liver antioxidant enzymes like superoxide dismutase, glutathione, LPO, CAT along with the effect on lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) was evaluated in the cotton pellet-induced granuloma model. Atorvastatin and rosuvastatin showed significant decrease (p < 0.05) in carrageenan- and formaldehyde-induced rat paw oedema and reduced granuloma formation in the cotton pellet-induced granuloma method (p < 0.01) while the levels of LDH and ALP were also significantly decreased (p < 0.05). The liver antioxidant enzyme levels were found to be restored (p < 0.05). Atorvastatin and rosuvastatin also showed antinociceptive activities (p < 0.05 and p < 0.01) in the acetic acid- and formalin-induced nociception in mice, while there was no significant activity in the hot plate method. The present findings suggest that atorvastatin and rosuvastatin possess dose-dependent antioxidant, analgesic, and anti-inflammatory activities.     

Antinociceptive,antipyretic, and anti-inflammatory activities of <Emphasis Type="Italic">Putranjiva roxburghii</Emphasis> Wall. leaf extract in experimental animals

The effects of the ether extract from the leaves of Putranjiva roxburghii (P. roxburghii) Wall. were assessed on nociceptive responses in mice by using writhing, hot plate, and formalin tests and the antipyretic activity was determined in yeast-induced fever in rats. Anti-inflammatory activities were also investigated using carrageenin-induced paw edema in rats and croton oil-induced ear and anus edemas. The ether extract (100, 200, and 400 mg/kg, p.o.) of P. roxburghii dose-dependently produced analgesic activity in acetic acid-induced writhing in mice. The extract had no significant effect in the hot plate test in mice. At the dose of 400 mg/kg, the extract significantly suppressed the licking activity in the late phase of the formalin test in mice and decreased fever induced by yeast in rats. The extract exhibited moderate inhibitory activity of inflammation in carrageenin-induced paw edema in rats. The extract inhibited croton oil-induced ear edema in a dose-dependent manner (1.25, 2.5, and 5.0 mg/ear) in mice. The extract decreased anus edema induced by croton oil at the high dose of 800 mg/kg in rats. The results indicated that the ether extract of P. roxburghii leaves possesses analgesic, antipyretic, and anti-inflammatory activities.     

Anti-inflammatory, analgesic and antipyretic activity of aqueous extract of fresh leaves of Coccinia indica

This study was aimed to evaluate both post- and pre-treatment anti-inflammatory activities of the aqueous extract of fresh leaves of Coccinia indica in rats using the carrageenan-induced paw oedema method at various dose levels. Analgesic and antipyretic properties were evaluated using tail flick model and yeast-induced hyperpyrexia, respectively. Ceiling effect of the extract was observed at 50 mg/kg in pre-treatment carrageenan test. In post-treatment studies, a dose-dependent anti-inflammatory effect was observed in the dose range of 25–300 mg/kg. The effect was equivalent to diclofenac (20 mg/kg) at 50 mg/kg but it was significantly pronounced at higher doses. Effectiveness of extract in the early phase of inflammation suggests the inhibition of histamine and serotonin release. The extract produced marked analgesic activity comparable to morphine at 300 mg/kg, which suggests the involvement of central mechanisms. A significant reduction in hyperpyrexia in rats was also produced by all doses of extract with maximum effect at 300 mg/kg comparable to paracetamol. In conclusion, this study has established the anti-inflammatory activity, analgesic and antipyretic activity of C. indica and, thus, justifies the ethnic uses of the plant.     

Antinociceptive and anti-inflammatory effects of the ethanol extract of Alpinia conchigera rhizomes in various animal models

Alpinia conchigera Griff. (Zingiberaceae), locally known to the Malays as “lengkuas ranting”, is native to Peninsular Malaysia. The Malays traditionally used it to treat infection and rashes, and as a health drink. This study evaluated the analgesic and anti-inflammatory activities of the ethanol extract of A. conchigera rhizomes in mice and rats, respectively. The analgesic activity was elucidated using the acetic acid-induced writhing test, hot plate test, and formalin test, while the anti-inflammatory activity was determined using carrageenan-induced paw edema. The extract (30, 100, and 300?mg/kg) given intraperitoneally (i.p.) exhibited antinociceptive and anti-inflammatory activities in all tests used. The range of percentage of analgesia obtained for all doses of extract in the writhing test was 50–92%, and in the early and late phases of the formalin test was 25–62% and 63–98%, respectively. In addition, naloxone (5?mg/kg) given subcutaneously (s.c.) was found to reverse the extract (300?mg/kg)-induced antinociceptive activity in the writhing, hot plate, and formalin tests. Based on the results obtained, it can be concluded that the ethanol extract of A. conchigera rhizomes possessed a peripheral and central antinociceptive activity that was mediated, in part, via the opioid receptor, as well as anti-inflammatory activity.     

Analgesic and anti-inflammatory activity of β-sitosterol isolated from Nyctanthes arbortristis leaves

Nyctanthes arbortristis Linn. (Oleaceae) is one of the well-known Indian medicinal plant. Various extracts of leaves of the plant were screened for analgesic activity by hot plate test and acetic acid-induced writhings and anti-inflammatory activity by carrageenan-induced hind paw edema method at the dose of 50?mg/kg, i.p. Petroleum ether extract was found to be most active and hence subjected to activity-guided fractionation. Results showed that β-sitosterol (5, 10 and 20?mg/kg, i.p.) was responsible for the significant and dose-dependent activity comparable with the standard extract. β-Sitosterol from N. arbortristis leaves might be responsible for analgesic and anti-inflammatory activity.     

Evaluation of the analgesic and anti-inflammatory activities of <Emphasis Type="Italic">Curcuma mangga</Emphasis> Val and Zijp rhizomes

The effects of Curcuma mangga ethanolic extract (CME) and its fractions, e.g., aqueous, chloroform, ethyl acetate, and hexane fractions, from C. mangga rhizome were investigated on nociceptive responses using writhing, hot plate, and formalin tests in mice and inflammatory models using carrageenan-induced rat paw edema and croton oil-induced mouse ear edema. The results showed that CME and all fractions (200 mg/kg, p.o.) significantly reduced the number of writhings. Oral administration (p.o.) of CME, chloroform, and hexane fractions (200 mg/kg) significantly prolonged the latency time, whereas aqueous and ethyl acetate fractions were inactive. The activities of CME, chloroform, and hexane fractions were abolished by naloxone (2 mg/kg, intraperitoneal (i.p.)). CME and all fractions at the dose of 200 mg/kg significantly produced antinociception in both early and late phases of the formalin test. CME, chloroform, and hexane fractions were more prominent in licking inhibition than those of the aqueous and ethyl acetate fractions. CME and all fractions (150 mg/kg, p.o.) showed significant reduction of rat paw edema. The order of activity on inhibition of paw edema at 4 h was chloroform fraction > hexane fraction > ethyl acetate fraction > CME > aqueous fraction. When topically applied at 0.5 mg/ear, CME and all fractions suppressed ear edema induced by croton oil. CME and chloroform fraction showed a greater inhibition by 53.97 and 50.29%, respectively. These results suggested that CME and its fractions, especially chloroform and hexane fractions from C. mangga rhizome, possessed centrally acting analgesic as well as anti-inflammatory activities.     

Methanol extract from mycelium of endophytic fungus Rhizoctonia sp. induces antinociceptive and anti-inflammatory activities in mice

The present study aimed to elucidate the antinociceptive and anti-inflammatory properties of the methanol extract from the mycelium of the endophytic fungus Rhizoctonia sp. (MEMRh) in mice. The antinociceptive activity was assessed using the abdominal constriction, hot plate, and formalin tests. The anti-inflammatory activity was assessed using a murine model of paw edema. Intraperitoneal administration of MEMRh (0.1, 1, 10 and 100?mg/kg, i.p.) produced an inhibition of acetic acid-induced writhing in mice for at least 8?h. In addition, all doses tested of the methanol extract were able to prevent thermal nociception in the hot-plate test. Furthermore, treatment with MEMRh (10?mg/kg, i.p.) inhibited both the early and late phases of formalin-induced nociception. This antinociceptive effect exhibited by MEMRh in the formalin test was reversed by the systemic administration of naloxone. MEMRh produced inhibition in a carrageenan-induced edema model at a dose of 10?mg/kg. The same extract also displayed significant activity against a histamine- or PGE(2)-induced edema model. The experimental data demonstrated that MEMRh showed remarkable anti-inflammatory and antinociceptive activities. Further studies are warranted to define and isolate the active anti-inflammatory and antinociceptive components from this endophytic fungus, which may yield effective agents for the treatment of inflammatory disorders.     

Analgesic and anti-nociceptive activity of hydroethanolic extract of Drymaria cordata Willd

Objectives:

To study the analgesic and anti-nociceptive activity of hydroethanolic extract of Drymaria cordata Willd.

Materials and Methods:

Wistar rats and Swiss albino mice were used for studying analgesic and anti-nociceptive activity of Drymaria cordata hydroethanolic extract (DCHE) at doses 50, 100 and 200 mg/kg p.o. Various models viz. acetic acid induced writhing model (female mice), Eddy''s hot plate (mice) and tail flick model (rat) for analgesic study and formalin-induced paw licking model (mice) were used for anti-nociceptive study.

Results:

In acetic acid induced writhing model, effect of DCHE was better than the standard drug- indomethacin 10 mg/kg (p.o.). In the hot plate model, the maximum effect was observed at 60 min at a dose of 200 mg/kg p.o., which was higher than the standard drug morphine sulfate (1.5 mg/kg i.p.), whereas in the tail flick model, effect was comparable with morphine sulfate. In formalin-induced paw licking model, administration of DCHE completely abolished the early phase at 100 and 200 mg/kg p.o. and in the late phase, the effect of DCHE (200 mg/kg p.o.) was higher than indomethacin (10 mg/kg p.o.).

Conclusion:

DCHE was effective in both non-narcotic and narcotic models of nociception, suggesting its possible action via peripheral and central mechanism. It also abolished the early phase in formalin-induced paw licking model, suggesting complete inactivation of C-fiber at higher dose. The activity can be attributed to the phyto-constituents viz tannins, diterpenes, triterpenes and steroids present in the DCHE extract. In conclusion, DCHE can be developed as a potent analgesic and anti-nociceptive agent in future.     

Anti-inflammatory and analgesic effects of 6α,7β–dihydroxy-vouacapan-17β-oic acid isolated from <Emphasis Type="Italic">Pterodon emarginatus</Emphasis> Vog. fruits

6α,7β-dihydroxy-vouacapan-17β-oic (tricyclic furanoid diterpene; DHVO) acid was isolated from the hexane extract of Pterodon emarginatus fruits and evaluated for anti-inflammatory and analgesic effects using an assay that induces paw oedema with carrageenan, dextran and prostaglandin E₂ (PGE₂) in rats and the writhing and formalin tests in mice. Oral administration of 50 mg/kg DHVO significantly inhibited carrageenan-induced oedema formation by 24% (p < 0.05). This treatment did not inhibit dextran-induced oedema but was effective when the inflammatory effect was triggered by PGE₂, inhibiting oedema formation by 39% (p < 0.05). In the writhing test, doses of 50, 200 and 400 mg/kg resulted in a dose-dependent effect with a correlation coefficient (r) of 0.983 (F = 29.04, ANOVA). Doses of 50 and 100 mg/kg inhibited both the neurogenic and inflammatory phases (p < 0.05) in the formalin test but were not effective for increasing the lag time in the hot plate test. Together, these results suggest that DHVO has both anti-inflammatory and peripheral analgesic effects.     

Evaluation of the anti-inflammatory property of the extract of <Emphasis Type="Italic">Combretum micranthum</Emphasis> G. Don (Combretaceae)

A methanol extract of Combretum micranthum leaves was studied for anti-inflammatory activity in rats and mice using the carrageenan-induced rat paw oedema and the acetic acid-induced vascular permeability in mice. The effect of the extract on cellular-type inflammation was also investigated in the cotton pellet granuloma in rats. The extract (50, 100 mg/kg) significantly (P < 0.05) inhibited oedema production induced by carrageenan in rats. Increased vascular permeability caused by acetic acid injection was also inhibited by the extract, within the same dose range. C. micranthum extract (100 mg/kg) inhibited granuloma formation in rats to a similar degree as indomethacin (5 mg/kg). These results provide evidence for the anti-inflammatory property of C. micranthum leaves.     

Anti-inflammatory,analgesic, and antioxidant activities of Pisonia aculeata: Folk medicinal use to scientific approach

Context: Pisonia aculeata leaves (Nyctagenaceae), a Folk medicinal plant used in the treatment of several inflammation, pain, and oxidative stress associated diseases.

Objective: To evaluate anti-inflammatory, analgesic, and antioxidant potential of crude methanol extract of P. aculeata leaves (MEPA).

Materials and methods: Analgesic and anti-inflammatory activities of MEPA (250 and 500?mg/kg) were evaluated using writhing, formalin, hot plate, tail flick, carrageenan-induced paw edema test, and membrane stabilizing activity. Free radical scavenging activity, total phenolic and flavonoid contents of MEPA were also determined using standard methods.

Results: Oral administration of MEPA showed significant (p < 0.001) inhibition of paw edema, pronounced at 4?h and 5?h after carrageenan injection, and at 200 µg/mL exerts 77.67 and 38.51% protective effect against hypotonic solution and heat induced hemolysis, respectively. MEPA (250 and 500?mg/kg) produced 35.21 and 79.14% inhibition of acetic acid-induced writhing. Furthermore, MEPA (500?mg/kg) inhibited 49.19% early and 73.14% late phase of formalin-induced hypernociception. In contrast, a lower dose of MEPA did not prevent hot plate induced nociception, while in the tail immersion method, pronounced analgesic activity was observed between 1 and 4?h postdosing. The extract possesses significant in vitro antioxidant activity and a lipid peroxidation inhibition effect. Total phenolic and total flavonoid content in MEPA were 87.99?±?0.87?mg GAE/g and 58.98?±?0.01?mg QE/g, respectively.

Discussion and conclusion: Our findings confirmed the analgesic, anti-inflammatory and antioxidant activities of Pisonia aculeata leaves. Contents of flavonoids and phenolic compounds in extract could be correlated with its observed biological activities.     

Antinociceptive effects of the extracts of <Emphasis Type="Italic">Xylopia parviflora</Emphasis> bark and its alkaloidal components in experimental animals

In the present study, we attempted to elucidate the antinociceptive activity of Xylopia parviflora bark using the acetic acid-induced writhing test, hot plate test, and formalin test in mice. The MeOH extract (100 and 200 mg/kg, administered intraperitoneally (i.p.)) had an antinociceptive effect demonstrated by its inhibitory effects on writhing number induced by acetic acid. Three alkaloidal fractions exhibited significant antinociceptive effects in three animal models; the chloroform-soluble fraction, including secondary and tertiary alkaloids, exhibited the strongest effect. This result supported its use in folk medicine as an analgesic agent. We tested the main alkaloids of these fractions for their antinociceptive effects to clarify the active components. (+)-Corytuberine (6.3 and 12.5 mg/kg, i.p.) showed very strong activity, had a significant antinociceptive effect in the acetic acid-induced writhing test (with 49.4 and 98.9% reduction of writhes), in the hot plate test, and in the formalin test (with 55.4 and 90.6% inhibition during the first phase, and 73.9 and 99.9% during the second phase, respectively). (+)-Glaucine (12.5 and 25 mg/kg, i.p.) showed strong activity in three animal models, too. The activity of these compounds was also observed following oral administration in the acetic acid-induced writhing test.     

Analgesic and anti-inflammatory effect of aqueous extract of the stem bark of <Emphasis Type="Italic">Allanblackia gabonensis</Emphasis> (Guttiferae)

Allanblackia gabonensis (Guttiferae) is a plant used in the African traditional medicine as remedies against pain, rheumatism, inflammations. In the present work, the analgesic effect of aqueous extract has been evaluated using acetic acid, formalin, hot-plate test, tail immersion and paw-pressure test. The anti-inflammatory effect of this extract was also investigated on carrageenan, histamine or serotonin induced by paw oedema. Aqueous extract of stem bark of A. gabonensis administrated p.o. showed significant activity against paw oedema induced by carrageenan, with a maximum percentage of inhibition reaching the 74.01% at the preventive test at a dose of 200 mg/kg. A. gabonensis exhibited a significant reduction of paw oedema induced by both histamine and serotonin with a maximal inhibition of 56.94% (200 mg/kg) and 40.83% (100 mg/kg), respectively. It showed significant protective effects against chemical stimuli (acetic acid and formalin) in the mouse. Administered orally at the doses of 100–400 mg/kg, exhibited protective effect of at least 69.78% on the pain induced by acetic acid and also reduced first (67.18% at 200 mg/kg) and second (83.87% at 400 mg/kg) phase of pain-induced par formalin. It also produced a significant increase of the threshold of sensitivity to pressure and hot plate-induced pain in the rats. These results suggest a peripheral and central analgesic activities as well as an anti-inflammatory effect of the stem bark of A. gabonensis.     

Evaluation of analgesic and anti-inflammatory activities of Nectandra megapotamica (Lauraceae) in mice and rats

The bioactivity-guided phytochemical investigation of the crude hydralcoholic extract of Nectandra megapotamica was carried out using the abdominal constriction test in mice, which led to the isolation of three active compounds: alpha-asarone (1), galgravin (2) and veraguensin (3). The crude extract (EBCA, 300 mg kg(-1)) and isolated compounds 1,2, and 3, at different doses, were evaluated using the acetic acid-induced abdominal constriction test in mice, carrageenan-induced paw oedema in rats, and hot plate tests in rats. The EBCA showed a significant effect in the abdominal constriction and hot plate tests, but did not show activity in the rat paw oedema assay. All isolated compounds displayed activity in the abdominal constriction test, but only compound 1 was active in the hot plate test. Compounds 2 and 3 displayed activity in the anti-inflammatory assay. It was suggested that the analgesic effects obtained for EBCA could be due mainly to the presence of its major compound, alpha-asarone (1).     

The antinociceptive and anti-inflammatory effects of Salvia officinalis leaf aqueous and butanol extracts

Context: The leaf of sage Salvia officinalis L. (Lamiaceae) is reputed in the folk medicine of Arabia, and Jordan in particular, to relieve pain associated with gastrointestinal disturbance.

Objectives: Evaluation of the antinociceptive and anti-inflammatory activities of aqueous and butanol extracts of S. officinalis leaf.

Materials and methods: The analgesic effects of the aqueous extract (10, 31.6, 100, 316, 1000?mg/kg) and butanol extract (10, 31.6, 100, 316?mg/kg) were studied using the hot-plate test for mice and the formalin-induced paw licking in rats. The effects were compared to those of morphine and the influence of naloxone on these effects was also evaluated. The same concentrations of both extracts were used to evaluate their anti-inflammatory effects using the cotton pellet granuloma and carrageenan-induced paw edema in rats.

Results: The aqueous extract (10, 31.6, 100, 316, 1000?mg/kg) and butanol extract (10, 31.6, 100, 316?mg/kg) caused analgesic effect in the hot-plate latency assay as well as in early and late phases of formalin-induced paw licking in rats. These effects were reduced by the opioid receptor antagonist, naloxone (5?mg/kg). The same range of doses of both extracts caused dose-dependent inhibition of carrageenan-induced paw edema in rats as well as inhibition of cotton pellet granuloma.

Discussion and conclusion: These observations suggest that the sage leaf aqueous and butanol extracts have analgesic and anti-inflammatory effects, confirming the traditional use of this plant for pain alleviation.     

Anti-inflammatory activity of aqueous leaf extract of Chromolaena odorata

The anti-inflammatory activity of the aqueous extract of Chromolaena odorata was investigated in rats using the carrageenan-induced oedema, cotton pellet granuloma and formalin-induced oedema methods. The extract was administered orally at doses of 25, 50, 100 and 200 mg/kg. In the carrageenan method the paw oedema was significantly reduced by all the doses of the extract administered, with the 200 mg/kg dose producing the highest oedema inhibition (80.5%). In the cotton pellet method, granuloma weight was significantly reduced from 14 ± 0.1 to 9.0 ± 0.1 mg, while in the formaldehyde induced arthritis the extract inhibited the oedema during the 10-day period. In conclusion, this study has established the anti-inflammatory activity of C. odorata and, thus, justifies the traditional uses of the plant in the treatment of wounds and inflammation.     

Studies on the anti-inflammatory and anti-nociceptive effects of melatonin in the rat.

The present study aimed to evaluate the anti-inflammatory and anti-nociceptive effects of melatonin in the rat. Acute inflammation was induced by sub-plantar injection of carrageenan (1%) in the rat hind paw. The rats received vehicle or drug 30 min before carrageenan administration and were evaluated for paw oedema at 1, 2, 3, and 4 h post-carrageenan. The induced inflammation and the formation of oedema were determined by measurement of the paw thickness. Nociception was tested by determining vocalization following electrical stimulation of the tail. Given intraperitoneally (i.p.) 30 min before carrageenan, melatonin caused significant and a dose-dependent reduction of hind paw swelling induced by carrageenan. At doses of 0.5 and 1 mg kg(-1), melatonin inhibited the carrageenan-induced oedema by 20.5 and 29.6% versus control values at 4 h post-carrageenan, respectively. Melatonin (0.5 and 1 mg kg(-1), i.p.) 30 min beforehand displayed anti-nociceptive effect in the electric stimulation of the rat tail test, increasing nociceptive thresholds to electrically-induced pain at 4 h post-treatment by 29.6 and 39.5%, respectively. Melatonin given simultaneously with the non-selective COX-1 and COX-2 inhibitor indomethacin (5 mg kg(-1), i.p.) 30 min prior to carrageenan, enhanced the anti-inflammatory effect of the latter in the carrageenan-induced paw oedema model by 23%. Melatonin (0.5 mg kg(-1), i.p.) increased the anti-nociceptive effect of indomethacin (5 mg kg(-1), i.p.). Meanwhile, the anti-inflammatory and anti-nociceptive effect of the highly selective COX-2 inhibitor rofecoxib (2.25 mg kg(-1), i.p.) was only slightly increased by melatonin administration at 0.5 mg kg(-1). Melatonin enhanced the anti-inflammatory effect of cysteamine (300 mg kg(-1), s.c.) in the carrageenan-induced paw oedema. Melatonin (20 and 40 microg per paw) given prior to carrageenan into the rat hind paw was devoid of anti-inflammatory effect. These results indicate that melatonin possesses anti-inflammatory and anti-nociceptive properties in the rat and enhance those of indomethacin. This effect is likely to be centrally mediated.