naloxone and Edema

Rhus genus is commonly known as sumac and widely used in the folk medicine. Rhus virens is a plant commonly used to treat diabetes or pain in the northern territory of Mexico. Even though R. virens is used in the folk medicine there is still a lack of evidence about the pharmacological effect of this species.. The aim of this study was to determine the antinociceptive, anti-inflammatory and antioxidant effect of R. virens through a bio-guided chemical separation.. The aqueous, methanolic, and hexane extract of R. virens were obtained and tested in the formalin test, TPA-induced ear edema, and DPPH, ABTS, and FRAP assay. Also, possible interaction of pain pathways was studied using naloxone, bicuculline, L-NAME, ODQ, and glibenclamide in the formalin test in mice.. Rhus virens methanolic extract (30 mg/kg, p.o.) produced higher antinociceptive activity in both the early and late phases of the formalin test (35.0 and 52.9%, respectively). Also, pre-administration with naloxone, bicuculline, L-NAME, ODQ and glibenclamide prevented the antinociceptive effect of R. virens in the early phase of the formalin test. Meanwhile, only naloxone and bicuculline prevented the antinociceptive effect on the late phase of the formalin test. Chemical separation of methanolic extract allowed to isolate 1,2,3,4,6-penta-O-galloyl-glucopyranose (PGG), it was tested in the formalin test, producing an antinociceptive effect on the late phase of the formalin test. On the other hand, topical application of the derivatives of R. virens methanolic extract produced an anti-inflammatory effect in the TPA-induced ear edema, being PGG an anti-inflammatory molecule. Lastly, radical scavenging activity was higher in the extracts of higher polarity, comparable to the standard used Camellia sinensis.. In conclusion, R. virens produce an antinociceptive, anti-inflammatory and free-radical scavenging activity. The antinociceptive effect could be related to the opioidergic, GABAergic, and NO-GMPc-K + ATP channels pathways. These effects could be partially produced by the presence of PGG.

Topics: Adenosine Triphosphate; Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Bicuculline; Edema; Glyburide; Hexanes; Mice; Naloxone; NG-Nitroarginine Methyl Ester; Pain; Plant Extracts; Plant Leaves; Rhus

Gastric ulcer induced by NSAIDs is the major medical concern and researchers are utilizing several approaches to combat this medical issue. In the current study, we investigated the efficacy of thiadiazinethione derivative (2,2'(2-thioxo-1,3,5-thiadiazinane-3,5-diyl) diacetic acid, as new less ulcerogenic compound.. 2,2'(2-thioxo-1,3,5-thiadiazinane-3,5-diyl) diacetic acid was evaluated using standard animal models including hot plate, writhing test and formalin induced nociceptive models. Anti-inflammatory activity was assessed via carrageenan-induced paw oedema model. Involvement of opioidergic nociceptive mechanism was confirmed via naloxone administration in hot plat assay. The gastro-ulcerogenic potential of test and standard compounds were evaluated via NSAID-induced pyloric ligation model followed by standard histopathological and biochemical analysis.. In acetic acid-induced writhing test, our compound significantly reduced abdominal constrictions at the tested doses of 15 (. Our findings suggests that our test compound has desirable anti-nociceptive and anti-inflammatory potentials with less propensity to cause gastric ulcer.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Carrageenan; Edema; Formaldehyde; Naloxone; Stomach Ulcer; Tramadol; Ulcer

Eugenia uniflora (Myrtaceae) is a species native to Brazil and has a traditional use in the treatment of inflammation.. To evaluate the anti-inflammatory and antinociceptive effects, and the involvement of opioid receptors in the antinociceptive activity of extract and fractions from Eugenia uniflora leaves.. TLC and HPLC were used to characterize the spray-dried extract (SDE) and fractions. In the in vivo assays, Swiss (Mus musculus) mice were used. Carrageenan-induced hind-paw edema and carrageenan-induced peritonitis models were used to determine the anti-inflammatory effect of the extract (50, 100, or 200 mg/kg). Acetic acid-induced writhing, tail-flick, and formalin tests were used to determine the antinociceptive effect of the extract (50, 100, or 200 mg/kg). The aqueous (AqF) and ethyl acetate (EAF) fractions (6.25, 12.5, and 25 mg/kg) were then combined with naloxone to evaluate the involvement of opioid receptors in the antinociceptive activity.. In this work, the TLC and HPLC analysis evidenced the enrichment of EAF, which higher concentration of gallic acid (5.29 ± 0.0004 %w/w), and ellagic acid (1.28 ± 0.0002 %w/w) and mainly myricitrin (8.64 ± 0.0002 %w/w). The extract decreased the number of total leukocytes and neutrophils in the peritoneal cavity (p < 0.05), at doses of 100 and 200 mg/kg and showed significant inhibition in the increase of paw edema volume (p < 0.05). The treatment per oral route (doses of 50, 100, and 200 mg/kg) significantly reduced the nociceptive response in acetic acid-induced abdominal writhing (p < 0.05). The effect of the extract on the tail-flick test showed a significant increase in latency time of animals treated at doses of 200 and 100 mg/kg (p < 0.05). The extract and ethyl acetate fraction reduced the nociceptive effect in both phases of formalin at all tested doses. The naloxone reversed the antinociceptive effect of EAF, suggesting that opioid receptors are involved in mediating the antinociceptive activity of EAF of E. uniflora in the formalin test.. The current study demonstrates the anti-inflammatory and analgesic activities of water: ethanol: propylene glycol spray-dried extract from E. uniflora leaves using in vivo pharmacological models in mice. Our findings suggest that spray-dried extract and ethyl acetate fraction exhibit peripheral and central antinociceptive activity with the involvement of opioid receptors that may be related to the presence of flavonoids, mainly myricitrin.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Edema; Ethanol; Eugenia; Mice; Naloxone; Pain; Plant Extracts; Propylene Glycols; Receptors, Opioid; Water

The current work examined the pharmacological potential of a selected flavanone derivative 2-hydroxyflavanone as a promising remedy for the treatment and management of pain. The selected flavanone derivative (2-HF) was evaluated for its analgesic and anti-inflammatory potentials following standard pharmacological protocols including hot plate, acetic acid-induced writhing and tail immersion tests. Naloxone and pentylenetetrazol were used to evaluate the potential implication of GABAergic and opioidergic mechanisms. The anti-inflammatory potential of 2-HF was confirmed using carrageenan-, serotonin- and histamine-induced paw edema models as well as a xylene-induced ear edema model. Furthermore, the anti-neuropathic potential of 2-HF was tested using a cisplatin-induced neuropathic pain model. Our sample, at the tested concentrations of 15, 30 and 45 mg kg

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Cisplatin; Disease Models, Animal; Edema; Flavanones; Gabapentin; Hyperalgesia; Inflammation; Naloxone; Neuralgia; Pentylenetetrazole; Rodentia

Eugenia pohliana DC.(Myrtaceae) is used in folk medicine by communities in Brazil. However, there are no reports on its biological activity. This is the first study to identify the components of E. pohliana essential oil (EpEO) and evaluate their antinociceptive and anti-inflammatory activities in an in vivo model at doses of 25, 50, and 100 mg/kg. The essential oil (EO) was obtained by hydrodistillation, and the analysis was performed by gas chromatography coupled with mass spectrometry. Antinociceptive activity was evaluated by writhing tests, tail movement, and formalin (neurogenic and inflammatory pain); naloxone was used to determine the nociception mechanism. Anti-inflammatory activity was assessed by oedema and peritonitis tests. We found that (E)-β-caryophyllene (BCP) (15.56%), δ-cadinene (11.24%) and α-cadinol (10.89%) were the major components. In the writhing test, there was a decrease in writing by 42.95-70.70%, in the tail movement, an increase in latency time by 69.12-86.63%, and in the formalin test, there was a reduction in pain neurogenic by 29.54-61.74%, and inflammatory pain by 37.42-64.87%. The antinociceptive effect of EpEO occurs through the activation of opioid receptors. In addition, a reduction in inflammation by 74.93‒81.41% was observed in the paw edema test and inhibition of the influx of leukocytes by 51.86‒70.38% and neutrophils by 37.74‒54.72% in the peritonitis test. It was concluded that EpEO has antinociceptive effect by the opioid pathway, as shown by the inhibitory effect of naloxone, and anti-inflammatory actions, and that its use does not cause hemolytic damage or behavioral change.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Edema; Eugenia; Inflammation; Mice; Myrtaceae; Naloxone; Nociception; Oils, Volatile; Pain; Peritonitis; Plant Extracts

Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are gut derived hormones. GLP-1 and GLP-2 were shown to have pleiotropic effects in intestinal and pancreatic diseases.. We aimed to investigate the activities of GLP-1 and GLP-2 on nociception and inflammation in mice, involving their actions on serotonergic, nitrergic, and opioidergic systems.. Antinociceptive and anti-inflammatory activities of intraperitoneally injected GLPs were evaluated in hotplate latency test, formalin-induced behavioral, and paw edema tests. Ondansetron, a selective 5-HT. GLP-1 (0.2 mg/kg) and GLP-2 (0.05, 0.2 mg/kg) significantly increased pain threshold. GLP-1 (0.2 mg/kg) and GLP-2 (0.05, 0.1, 0.2 mg/kg) significantly decreased formalin-induced licking and shaking behaviors. GLP-1 or GLP-2 showed no significant inhibitory action on formalin-induced swelling in paws of mice. Antinociceptive actions of GLP-1 and GLP-2 were significantly decreased with ondansetron and naloxone, and paw shaking behavior significantly increased with naloxone. GLP-1 and GLP-2 did not impair rotarod performance, and did not cause a significant hypoglycemic effect in our normoglycemic mice after rotarod test.. These finding indicated that the antinociceptive and anti-inflammatory effect of GLP-1 was related to opioidergic system. Antinociceptive effect of GLP-2 was partially related to 5-HT3 serotonergic or opioidergic system in hotplate test. However, the anti-inflammatory effect of GLP-2 was not directly related to 5-HT3, NO or opioids.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Edema; Female; Glucagon-Like Peptides; Male; Mice; Mice, Inbred BALB C; Naloxone; Narcotic Antagonists; Nitric Oxide; Nociception; Pain; Pain Measurement; Plant Extracts; Receptors, Serotonin, 5-HT3; Rotarod Performance Test; Serotonin 5-HT3 Receptor Antagonists

Background Tetracera alnifolia Willd. (Dilleniaceae) is used in traditional African Medicine for the treatment of headache, abdominal pain, and rheumatism. Hence, this study sought to investigate the antinociceptive and anti-inflammatory effects of the hydroethanolic leaf extract of T. alnifolia (HeTA) in rodents. Methods Antinociceptive activity was evaluated using the acetic acid-induced writhing, formalin-/capsaicin-induced paw licking and hot plate tests in mice. The contribution of opioidergic, l-arginine-nitric oxide, and ATP-sensitive potassium channel pathways in HeTA-induced antinociception was also evaluated. The anti-inflammatory effect was assessed using the carrageenan-induced paw edema, xylene ear edema, cotton pellet granuloma, and complete Freund's adjuvant (CFA)-induced arthritis in rats. Results HeTA (100, 200, and 400 mg/kg, p.o.) produced significant (p<0.05) decrease in mean number of acetic acid-induced writhing, time spent licking paw in formalin, and capsaicin tests as well as time course increase in nociceptive reaction latency in hot plate test. HeTA-induced antinociception was prevented by pretreatment of mice with naloxone (non-selective opioid receptor antagonist), l-arginine (nitric oxide precursor), or glibenclamide (ATP-sensitive potassium channel blocker). HeTA (100 mg/kg, p.o.) produced a significant anti-inflammatory effect against carrageenan-induced rat paw edema (1-5 h), xylene-induced ear edema, cotton pellet-induced granuloma formation, and CFA-induced arthritis in rats. The effects of HeTA in various models were similar to the effect of the standard reference drugs. Conclusions Findings from this study showed that HeTA possesses antinociceptive effect possibly mediated through peripheral opioid receptors with activation of l-arginine-nitric oxide and ATP-sensitive potassium channel pathway as well as anti-inflammatory activity.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Arginine; Arthritis; Carrageenan; Dilleniaceae; Edema; Glyburide; Male; Medicine, African Traditional; Mice; Naloxone; Pain; Pain Measurement; Phytotherapy; Plant Extracts; Plant Leaves; Rats

The in vivo antiinflammatory and analgesic activities of the crude ethanol extract and chemical constituents of Clausena anisata roots were investigated. The crude extract, which was devoid of any visible acute toxicity, displayed significant antiinflammatory effect at the dose of 1000 mg/kg (p.o.) when assessed using the carrageenan-induced oedema model. In the acetic acid-induced writhing and hot plate tests, it produced a very significant (p < 0.001); dose- dependent analgesic effect, with maximum analgesic activity of 72.1% at 1000 mg/kg (p.o.). Phytochemical analysis of the crude extract resulted in the isolation of four coumarins (anisocoumarin B, osthol, imperatorin and xanthotoxol) and a carbazole alkaloid, heptaphylline. Among the isolated compounds, osthol and anisocournarin B produced the highest antiinflammatory activity at 9 mg/kg (p.o.): slightly better than the positive control, indomethacin. Except for xanthotoxol, all the isolated compounds administered at 6 mg/kg (p.o.) produced significant analgesic activity and higher than diclofenac; with- heptaphylline being the most potent (48.7%). The analgesic activity of anisocoumarin B (50.4%) was the highest among the isolates tested and the standard, tramadol, in the hot plate test. The nonselective opioid receptor antagonist, naloxone, abolished the analgesic effect of the crude extract and the tested isolates (anisocoumarin B and xanthotoxol) in the hot plate test suggesting an effect via the central opioidergic system. These findings provide the scientific basis for the use of C. anisata roots in traditional medicine as antiinflammatory and analgesic agents.

Topics: Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Clausena; Coumarins; Dose-Response Relationship, Drug; Edema; Ethanol; Magnetic Resonance Spectroscopy; Male; Mice; Mice, Inbred C57BL; Naloxone; Narcotic Antagonists; Pain Measurement; Plant Extracts; Plant Roots; Rats; Rats, Sprague-Dawley

Major attention has been on dietary and medicinal phytochemicals that inhibit or reverse abnormal conditions caused by nociceptive and inflammatory stimuli. Garcinia kola (Guttiferae) seed, known as "bitter kola", plays an important role in African ethno-medicine and traditional hospitality like in the treatment of inflammation, colds, bronchitis, bacterial, and viral infections. A number of useful phytochemicals have been isolated from the seed, and the most prominent of them is kolaviron (Garcinia bioflavonoid), which has been suggested to have antinociceptive and anti-inflammatory potentials. The aim of this experiment is to explore the mechanisms of action of the antinociceptive and anti-inflammatory potentials of kolaviron.. The probable mechanisms of action of kolaviron were assessed by using naloxone, prazosin, and atropine to investigate the involvement of adrenergic, opioidergic, and cholinergic systems, respectively, using tail flick, the acetic acid-induced writhing, formalin-induced paw licking, and carrageenan-induced paw edema models. Also, hematoxylin and eosin (H&E) staining was used to analyze the level of inflammation.. In the acetic acid-induced writhing test in mice, pretreatment with naloxone, prazosin, and atropine significantly reversed the antinociception effects of kolaviron (200 mg/kg) when compared with control and kolaviron groups. In the formalin-induced paw licking test in mice, there was a significant decrease on the antinociceptive effects of kolaviron in the late phase when compared with the control, while the pretreatment with naloxone and prazosin significantly reversed the antinociception of kolaviron but atropine did not have any significant decrease when compared with the kolaviron group. In the tail flick latency assay in rats, pretreatment with naloxone and prazosin significantly reversed the antinociception of kolaviron but atropine; however, did not have any significant increase when compared with the control and kolaviron groups. The result of the study also shows a highly significant inhibition of paw edema in the carrageenan-induced receiving kolaviron when compared with the vehicle carrageenan-induced groups. Histological staining also showed that kolaviron significantly reduced the infiltration of inflammatory cells in the paw tissues.. Kolaviron possesses antinociceptive and anti-inflammatory activity, both centrally and peripherally, which justifies its folkloric use to relieve pain and inflammation. It may be exerting its effects through mechanisms that involve opioidergic and adrenergic systems, and may not involve the cholinergic system.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Atropine; Carrageenan; Edema; Female; Flavonoids; Inflammation; Male; Mice; Naloxone; Pain; Phytotherapy; Plant Extracts; Prazosin; Rats; Rats, Wistar

Water immersion is widely used in physiotherapy and might relieve pain, probably by activating several distinct somatosensory modalities, including tactile, pressure, and thermal sensations. However, the endogenous mechanisms behind this effect remain poorly understood. This study examined whether warm water immersion therapy (WWIT) produces an antiallodynic effect in a model of localized inflammation and whether peripheral opioid, cannabinoid, and adenosine receptors are involved in this effect. Mice were injected with complete Freund's adjuvant (CFA; intraplantar; i.pl.). The withdrawal frequency to mechanical stimuli (von Frey test) was used to determine 1) the effect of WWIT against CFA-induced allodynia and 2) the effect of i.pl. preadministration of naloxone (a nonselective opioid receptor antagonist; 5 µg/paw), caffeine (a nonselective adenosine receptor antagonist; 150 nmol/paw), 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; a selective adenosine A1 receptor antagonist; 10 nmol/paw), and AM630 (a selective cannabinoid receptor type 2 antagonist; 4 µg/paw) on the antiallodynic effect of WWIT against CFA-induced allodynia. Moreover, the influence of WWIT on paw inflammatory edema was measured with a digital micrometer. WWIT produced a significant time-dependent reduction of paw inflammatory allodynia but did not influence paw edema induced by CFA. Naloxone, caffeine, DPCPX, and AM630 injected in the right, but not in the left, hind paw significantly reversed the antiallodynic effect of WWIT. This is the first study to demonstrate the involvement of peripheral receptors in the antiallodynic effect of WWIT in a murine model of persistent inflammatory pain.

Topics: Adenosine; Animals; Benzoxazines; Disease Models, Animal; Edema; Freund's Adjuvant; Hyperalgesia; Immersion; Indoles; Inflammation; Male; Mice; Morpholines; Naloxone; Naphthalenes; Narcotic Antagonists; Neurobiology; Pain Measurement; Receptor, Adenosine A1; Receptor, Cannabinoid, CB2; Receptors, Opioid; Water Purification

The Condalia buxifolia root bark infusion is used in traditional medicine in Brazil as antipyretic, anti-inflammatory and against dysentery. This study was designed to investigate whether the methanolic extract of the root bark of Condalia buxifolia (MECb) exhibits antinociceptive and anti-inflammatory effects in mice. Furthermore, also was investigated the involvement of glutamatergic and opioidergic system in the antinociceptive effect induced by MECb.. The antinociceptive and anti-inflammatory effects of intra-gastric gavage (i.g.) administered MECb (10-300 mg/kg) were evaluated in mice subjected to chemical (formalin, acetic-acid, glutamate) or thermal (hot plate) models of pain. The involvement of opioid system in the antinociceptive effect of the MECb was investigated in formalin test. Furthermore, a nonspecific effect of MECb was evaluated by measuring locomotor activity and exploratory behavior in open field test. Finally, was performed a phytochemical analysis of MECb.. The phytochemical analysis of MECb was performed through HPLC analysis showing that the alkaloid Condaline-A is the main constituent. The intragastric administration of MECb (100-300 mg/kg) significantly inhibited the nociception caused by acetic acid (48 ± 2%), inflammatory phase (49 ± 3%) and paw edema (32 ± 6) caused by formalin, and MECb (100mg/kg, i.g.) also inhibited nociception caused by glutamate (41 ± 7%). In addition, MECb (100-300 mg/kg, i.g.) increased the paw withdrawal latency in hot-plate test, without affecting the locomotor activity and exploratory behavior in open field test. Finally, the antinociceptive effects of MECb (100mg/kg, i.g.) were significantly reversed by naloxone (1mg/kg, i.p.) in the formalin test.. These data show, for the first time, that MECb has significant antinociceptive and anti-inflammatory effects, which appear to be related to the inhibition of the glutamatergic system and the activation of opioid mechanism, besides present central effects. These results support the use of Condalia buxifolia in traditional medicine and demonstrate that this plant has therapeutic potential for the development of phytomedicines with antinociceptive and anti-inflammatory properties.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Behavior, Animal; Edema; Female; Formaldehyde; Glutamic Acid; Hot Temperature; Medicine, Traditional; Mice; Motor Activity; Naloxone; Narcotic Antagonists; Pain; Phytotherapy; Plant Extracts; Plant Roots; Rhamnaceae

The present work reports the anti-inflammatory and antinociceptive activities of the ethanol extract obtained from the stem bark of Sterculia striata A. St.-Hil. & Naudin (Ss-EtOH) in the experimental models of edema induced by carrageenan, dextran, or histamin and nociception induced by chemical stimuli, such as acetic acid, formalin, capsaicin, or glutamate. The Ss-EtOH (50 mg/kg) promoted a marked inhibition on the hind paw edema induced by carrageenan or dextran (30% and 73%, respectively). Besides, Ss-EtOH (25 mg/kg) exhibited a slight activity (30%) on the hind paw edema induced by histamin. The Ss-EtOH (12.5 and 25 mg/kg) showed the antinociceptive activity on chemical stimuli induced by acetic acid (65.59% and 38.37%, respectively), formalin, in the initial (35.08% and 31.5%, respectively) and late phases (44.09% and 83.57%, respectively), capsaicin (43.77% and 51.31%, respectively), or glutamate (36.6% and 52.12%, respectively). Regarding the possible mechanism involved in the antinociceptive effect, Ss-EtOH (12.5 mg/kg) showed a decrease in the antinociceptive effect (65.8%) in the acetic acid model after pretreatment with naloxone. Thus, opioid mechanisms might be underlying this response.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Capsaicin; Carrageenan; Dextrans; Edema; Formaldehyde; Glutamic Acid; Histamine; Inflammation; Male; Mice; Naloxone; Pain; Phytotherapy; Plant Bark; Plant Extracts; Plant Stems; Rats, Wistar; Sterculia

Restraint stress modulates pain and inflammation. The present study was designed to evaluate the effect of acute restraint stress on inflammatory pain induced by subcutaneous injection of bee venom (BV). First, we investigated the effect of 1 h restraint on the spontaneous paw-flinching reflex (SPFR), decrease in paw withdrawal mechanical threshold (PWMT) and increase in paw volume (PV) of the injected paw induced by BV. SPFR was measured immediately after BV injection, and PWMT and PV were measured 2 h before BV and 2-8 h after BV. The results showed that acute restraint inhibited significantly the SPFR but failed to affect mechanical hyperalgesia. In contrast, stress enhanced significantly inflammatory swelling of the injected paw. In a second series of experiments, the effects of pretreatment with capsaicin locally applied to the sciatic nerve, systemic 6-hydroxydopamine (6-OHDA), and systemic naloxone were examined on the antinociception and proinflammation produced by acute restraint stress. Local capsaicin pretreatment inhibited BV-induced nociception and inflammatory edema, and had additive effects with stress on nociception but reduced stress enhancement of edema. Systemic 6-OHDA treatment attenuated the proinflammatory effect of stress, but did not affect the antinociceptive effect. Systemic naloxone pretreatment eliminated the antinociceptive effect of stress, but did not affect proinflammation. Taken together, our data indicate that acute restraint stress contributes to antinociception via activating an endogenous opioid system, while sympathetic postganglionic fibers may contribute to enhanced inflammation in the BV pain model.

Topics: Animals; Bee Venoms; Capsaicin; Disease Models, Animal; Edema; Hindlimb; Hyperalgesia; Inflammation; Male; Naloxone; Nociception; Oxidopamine; Pain; Rats; Rats, Sprague-Dawley; Restraint, Physical; Sciatic Nerve; Stress, Psychological; Sympathetic Nervous System

Artemisia scoparia (redstem wormwood) locally known as jhahoo or jaukay, is traditionally used in pain, inflammation and febrile conditions. So far, little or no scientific work has been reported to validate its folk uses in the alleviation of pain, fever and inflammation. The present study was designed to explore the analgesic, anti-inflammatory and antipyretic effects of the Artemisia scoparia hydromethanolic extract (ASHME), and to validate its traditional use in Asia.. This study made use of thermal (hot plate induced) and chemical (acetic acid induced) nociception models in mice. In addition, the mechanism of antinociception in hot plate test was further evaluated in the presence of caffeine (10mg/kg), naloxone (2mg/kg) and monosodium glutamate (1g/kg). While carrageenan induced rat paw edema and yeast induced mouse pyrexia models were used to test the anti-inflammatory and antipyretic activities.. Administration of single intraperitoneal doses (400mg/kg and 800 mg/kg) of ASHME significantly reduced the carrageenan induced paw edema in rats (P<0.05, P<0.001) by 54% and 74%, increased the thermal nociception time in the hot plate test up to 2- and 2.5-fold (P<0.01, P<0.001), inhibited the acetic acid induced writhings in mice by 41.12% and 61.53% (P<0.001), and attenuated the yeast induced pyrexia in mice by nearly 74% and 90% respectively (P<0.01, P<0.001). Caffeine (10mg/kg), naloxone (2mg/kg) and monosodium glutamate (1g/kg) significantly (P<0.001) abolished the anti-nociceptive response of ASHME (400mg/kg).. These findings suggest that the Artemisia scoparia hydromethanolic extract of ASHME possesses anti-nociceptive, anti-inflammatory and antipyretic potentials, which support its use, for the said conditions, in traditional medicine and should be further exploited for its use in clinical medicine.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antipyretics; Artemisia; Caffeine; Carrageenan; Edema; Female; Fever; Herb-Drug Interactions; Male; Methanol; Mice; Mice, Inbred BALB C; Naloxone; Pain; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Sodium Glutamate

Hemorphins, a family of atypical endogenous opioid peptides, are produced by the cleavage of hemoglobin β-chain. Hemorphins were proved to bind to the μ-opioid receptors (agonist) and angiotensin IV receptors (insulin-regulated aminopeptidase; IRAP) (inhibitor). Among the hemorphins, LVV-hemorphin-7 (LVV-H7) was found to be abundant and with a longer half life in the CNS. Using intrathecal and intracerebroventricular injections, LVV-H7 and angiotensin IV were given to the rats, which were then subjected to the plantar test and the tail-flick test. Our results showed that LVV-H7 attenuated carrageenan-induced hyperalgesia at the spinal level, which could not be reversed by the co-administration of naloxone. At the supraspinal level, LVV-H7 also produced a significant anti-hyperalgesia effect but with a lower extent. Angiotensin IV showed a similar anti-hyperalgesia effect at the spinal level, but had no effect at the supraspinal level. In the tail-flick test and paw edema test, both peptides showed no effect. These results suggest that LVV-H7 mainly exert the anti-hyperalgesia effect at the spinal level, possibly through IRAP but not μ-opioid receptors. In addition, we observed the expression of IRAP in the CNS of animals with/without carrageenan-induced hyperalgesia. Our results showed a significant expression of IRAP in the spinal cord of rats. However, there was no significant quantitative change of IRAP after the development of hyperalgesia. The serum level of LVV-H7 was also found to be with no change caused by hyperalgesia. These results indicated that the endogenous LVV-H7 and IRAP may not regulate the severity of hyperalgesia through a quantitative change.

Topics: Analgesics; Angiotensin II; Animals; Behavior, Animal; Carrageenan; Cystinyl Aminopeptidase; Dose-Response Relationship, Drug; Drug Therapy, Combination; Edema; Foot; Hemoglobins; Hyperalgesia; Male; Naloxone; Nociception; Peptide Fragments; Rats; Rats, Sprague-Dawley; Spinal Cord

Pyrexia, algesia and inflammation are associated with several pathological conditions. Synthetic drugs available for the treatment of these conditions cause multiple unwanted effects. Several studies are ongoing worldwide to find natural healing agents with better safety profile. The current study was thus aimed at evaluating antipyretic, analgesic and anti-inflammatory activities of the methanolic extract of whole plant of V. betonicifolia (VBME).. VBME was employed to assess antipyretic activity in yeast induced hyperthermia. Analgesic profile was ascertained in acetic acid induced writhing, hot plat and tail immersion test. Nevertheless, the anti-inflammatory activity was tested in carrageenan induced paw edema and histamine induced inflammatory tests. BALB/c mice were used at test doses of 100, 200 and 300 mg/kg body weight intra peritoneally (i.p).. In yeast induced pyrexia, VBME demonstrated dose dependently (78.23%) protection at 300 mg/kg, similar to standard drug, paracetamol (90%) at 150 mg/kg i.p. VBME showed a dose dependent analgesia in various pain models i.e. acetic acid, hot plat and tail immersion having 78.90%, 69.96% and 68.58% protection respectively at 300 mg/kg. However, the analgesic action of VBME was completely antagonized by the injection of naloxone like opiate antagonists. Similarly carrageenan and histamine induces inflammation was significantly antagonized by VBME, 66.30% and 60.80% respectively at 300 mg/kg.. It is concluded that VBME has marked antipyretic, analgesic and anti-inflammatory activities in various animal models and this strongly supports the ethnopharmacological uses of Viola betonicifolia as antipyretic, analgesic and anti-inflammatory plant.

Topics: Acetaminophen; Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Antipyretics; Behavior, Animal; Carrageenan; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Female; Fever; Histamine; Hot Temperature; Inflammation; Male; Mice; Mice, Inbred BALB C; Naloxone; Narcotic Antagonists; Pain; Phytotherapy; Plant Extracts; Tail; Viola; Yeasts

The neuropeptide oxytocin (OXT) contributes to the regulation of diverse cognitive and physiological functions including nociception. Indeed, OXT has been reported to be analgesic when administered directly into the brain, the spinal cord, or systemically. Although many authors have reported the analgesic effects of OXT, its mechanism has not been well elucidated. Recently, it has been also hypothesize that OXT, increasing intracellular concentration of calcium, could regulate the production of mediators, like endocannabinoids (eCB). It has been well documented that eCB are able to suppress pain pathways. The present study investigates the effect of OXT in paw carrageenan-induced pain. Intracerebroventricular (icv) administration of OXT, but neither intraperitoneal nor intraplantar route, induces an antihyperalgesic effect increasing paw withdrawal latency to mechanical or thermal stimuli. Our results clearly demonstrate that 3 and 6h following carrageenan challenge, central administration of OXT (30 ng/mouse) shows a significant antihyperalgesic activity. Moreover, for the first time, we demonstrate that CB1 receptor plays a key role in the antihyperalgesic effect of OXT. In fact our results show CB1 antagonist, but not the specific CB2 antagonist reduce OXT-induced antihyperalgesic effect. In addition, our data show that central OXT administration is able to reduce carrageenan-induced hyperalgesia but does not modify carrageenan-induced paw edema. Finally, using opioid antagonists we confirm an important role of opioid receptors. In conclusion, our experiments suggest that central administration of OXT reduces hyperalgesia induced by intraplantar injection of carrageenan, and this effect may work via cannabinoid and opioid systems.

Topics: Analgesics, Non-Narcotic; Animals; Carrageenan; Cyclooxygenase 2; Dose-Response Relationship, Drug; Edema; Hyperalgesia; Injections, Intraventricular; Male; Mice; Motor Activity; Naloxone; Narcotic Antagonists; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type II; Oxytocin; Pain; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Receptors, Opioid; Receptors, Oxytocin; Spinal Cord

The objectives of this work were to carry out a comparative chemical study and to evaluate the antinociceptive and anti-inflammatory activities of ethanol extracts (EtOHE) and vanilic acid (VA) from cultivated and wild Amburana cearensis A.C. Smith (Fabaceae), an endangered species used in Northeast Brazil for the treatment of asthma. The HPLC analysis of EtOHE, showed that coumarin (CM) and VA were the major constituents from the cultivated plant, while in the extract from the wild plant the major constituents were amburoside A (AMB) and CM. Pharmacological tests were performed with male Swiss mice or male Wistar rats acutely administered with 100-400mg/kg, p.o. of EtOHEs or 12.5-50mg/kg, p.o. of VA. EtOHEs from A. cearensis with 4, 7 or 9 months of cultivation significantly inhibited, from 32 to 64%, both phases of the formalin test in mice. Similar results were observed with the EtOHE from the wild species. VA significantly reduced both phases of the formalin test. This effect was partially reversed by naloxone. EtOHE from cultivated or wild A. cearensis inhibited the carrageenan (Cg)-induced mice paw edema. Furthermore, VA inhibited the paw edema and the leukocyte migration in rat peritoneal cavity induced by Cg. On the other hand, it did not inhibit the edema and the increase of vascular permeability induced by dextran in the rat paw. All together, these results indicate that the EtOHE from cultivated A. cearensis exhibit similar chemical and pharmacological profiles, as related to the wild plant. VA is, at least partially, responsible for these pharmacological effects. Its antinociceptive effect occurs by a mechanism partly dependent upon the opioid system, while the anti-inflammatory action was manifested in inflammatory processes dependent on polymorphonuclear cells and are probably related to the VA inhibition of cytokines as observed by others.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Capillary Permeability; Carrageenan; Dextrans; Edema; Fabaceae; Formaldehyde; Leukocytes; Male; Mice; Naloxone; Pain; Peritoneum; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Vanillic Acid

A new acylamino acid, bunodosine 391 (BDS 391), was isolated from the venom of the sea anemone Bunodosoma cangicum. The structure was elucidated by spectroscopic analyses (2D NMR, ESIMS/MS) and verified by its synthesis. Intraplantar injection of BDS 391 into the hind paw of a rat induced a potent analgesic effect. This effect was not altered by naloxone (an opioid receptor antagonist), but was completely reversed by methysergide (a serotonin receptor antagonist), indicating that the effect is mediated by activation of serotonin receptors.

Topics: Analgesics; Animals; Cnidarian Venoms; Edema; Hindlimb; Male; Molecular Structure; Naloxone; Narcotic Antagonists; Nuclear Magnetic Resonance, Biomolecular; Rats; Rats, Wistar; Receptors, Serotonin; Sea Anemones

The antioxidant, antinociceptive, and anti-inflammatory activities of the ethanolic extract from leaves of Combretum duarteanum (EEC) were assessed in rodents through in vitro tests. The antioxidant activity was investigated by using thiobarbituric acid reactive species (TBARS), hydroxyl radical-scavenging, and scavenging activity of nitric oxide assays. The antinociceptive activity was investigated by using acetic acid-induced writhing, formalin, and hot-plate tests in mice. The anti-inflammatory activity was assessed in rats by using the carrageenan-induced hind-paw edema test and arachidonic acid-induced paw edema test. EEC possesses a strong antioxidant potential according to the TBARS, nitric oxide, and hydroxyl radical-scavenging assays; it also presented scavenger activity in all in vitro tests. After intraperitoneal injection, EEC (100, 200, and 400 mg/kg) significantly reduced the number of writhes (38.1%, 90.6%, and 97.8%, respectively) in a writhing test and the number of paw licks during phase 1 (30.5% and 69.5%, higher doses) and phase 2 (38.1%, 90.6%, and 97.8%, all doses) of a formalin test when compared with the control group. Naloxone (1.5 mg/kg, intraperitoneally) antagonized the antinociceptive action of EEC (400 mg/kg), and this finding suggests participation of the opioid system. Administration of 200 and 400 mg/kg (intraperitoneally) of EEC exhibited an anti-inflammatory activity in the carrageenin test, which was based on interference with prostaglandin synthesis. This finding was confirmed by the arachidonic acid test. Together, these results indicate that properties of EEC might be further explored in the search for newer tools to treat painful inflammatory conditions, including those related to pro-oxidant states.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Arachidonic Acid; Carrageenan; Combretum; Dose-Response Relationship, Drug; Edema; Ethanol; Hydroxyl Radical; Male; Mice; Naloxone; Nitric Oxide; Pain; Pain Measurement; Plant Extracts; Plant Leaves; Rats; Rats, Wistar; Reactive Oxygen Species; Rodentia; Thiobarbituric Acid Reactive Substances

Byrsonima intermedia A. Juss. is popularly known as "murici pequeno" and is native to the Brazilian Cerrado. This species has been used as an antimicrobial, anti-hemorrhagic, anti-diarrheal and anti-inflammatory. Nevertheless, scientific information regarding Byrsonima intermedia is limited; there are no reports related to its possible anti inflammatory and antinociceptive effects. This study employed in vivo inflammatory and nociceptive models to evaluate the scientific basis for the traditional use of Byrsonima intermedia.. Carrageenan-induced paw edema, peritonitis and fibrovascular tissue growth induced by s.c. cotton pellet implantation tests were used to investigate the anti-inflammatory activity of Byrsonima intermedia aqueous extract (BiAE) in rats. Mechanical nociceptive paw, formalin and hot plate tests were used to evaluate the antinociceptive activity in mice. High-performance liquid chromatography (HPLC), phytochemistry screening and determination of total phenolics and flavonoids were used to determine the chemical profile of the BiAE.. BiAE at test doses of 30-300 mg/kg p.o. clearly demonstrated anti-inflammatory effects by reduced carrageenan-induced paw edema, by inhibited leukocyte recruitment into the peritoneal cavity and, in the model of chronic inflammation, by using the cotton pellet-induced fibrovascular tissue growth in rats. The extracts at test doses of 30-300 mg/kg p.o. clearly demonstrated antinociceptive activity in all tests. Administration of the opioid receptor antagonist naloxone completely inhibited the antinociceptive effect induced by BiAE (100 mg/kg).. BiAE markedly exhibits anti-inflammatory action in rats and antinociceptive activity in mice. Thus, it may be useful in the treatment of inflammatory hyperalgesic disorders, which supports previous claims of its traditional use.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Behavior, Animal; Carrageenan; Chromatography, High Pressure Liquid; Cotton Fiber; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Flavonoids; Formaldehyde; Granuloma, Foreign-Body; Hot Temperature; Lipopolysaccharides; Male; Malpighiaceae; Mice; Motor Activity; Naloxone; Narcotic Antagonists; Pain; Pain Measurement; Pain Threshold; Peritonitis; Phenols; Plant Bark; Plant Extracts; Plant Stems; Plants, Medicinal; Rats; Rats, Wistar; Time Factors

To explore the site of action of maprotiline, as an atypical antidepressant, on carrageenan-induced paw edema.. Male Wistar rats were used.. Firstly, the anti-inflammatory effect of systemic maprotiline (12.5, 25 and 50 mg kg(-1)) was assessed using a paw edema model. Secondly, different doses of maprotiline were administrated intracerebroventricularly, intrathecally and locally before carrageenan challenge. Finally, we tried to reverse the anti-inflammatory effect of maprotiline by propranolol (10 mg kg(-1)), prazosin (4 mg kg(-1)), yohimbine (10 mg kg(-1)), naloxone (4 mg kg(-1)) and mifepristone (5 mg kg(-1)).. Systemic, intracerebroventricular and subplantar application of maprotiline significantly inhibited peripheral edema, but intrathecal maprotiline did not alter the degree of paw swelling. The applied antagonists failed to change the anti-inflammatory activity of maprotiline.. These results demonstrate that maprotiline has a potent anti-inflammatory effect and this effect is linked to the peripheral and supraspinal actions of the drug.

Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-2 Receptor Antagonists; Adrenergic beta-Antagonists; Animals; Anti-Inflammatory Agents; Antidepressive Agents, Second-Generation; Carrageenan; Edema; Hormone Antagonists; Indomethacin; Injections, Spinal; Male; Maprotiline; Mifepristone; Naloxone; Narcotic Antagonists; Prazosin; Propranolol; Rats; Rats, Wistar; Yohimbine

50% ethanol extract (ASE) of Amaranthus spinosus (whole plant) has been evaluated for antinociceptive and antiinflammatory activities.. Analgesic and antiinflammatory activities were studied by measuring nociception by formalin, acetic acid, hot plate, tail immersion method while inflammation was induced by carrageenan.. ASE had significant dose dependent percentage protection against acetic acid (0.6% of 10 ml) induced pain and the effects were also compared to aspirin, morphine and naloxone while formalin induced pain (0.05 ml of 2.5%) was significantly blocked only at higher dose (400mg/kg) in first phase. ASE significantly blocked pain emanating from inflammation at all the doses in second phase. The reaction time in hot plate was increased significantly and dose dependently where as pretreatment with naloxone rigorously reduced the analgesic potentials of ASE. Further in tail immersion test the same dose dependent and significant activity was observed. Aspirin had no effect on thermal induced pain i.e. hot plate and tail immersion tests but showed an effect on writhing test.. Our investigation show that Amaranthus spinosus possess significant and dose dependant antiinflammatory activity, it has also central and peripheral analgesic activity.

Topics: Acetic Acid; Amaranthus; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Carrageenan; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Formaldehyde; Hot Temperature; Male; Mice; Naloxone; Narcotic Antagonists; Pain; Phytotherapy; Plant Extracts

Cocos nucifera cultivated in Brazil is known as "coco-da-Bahia" or "coqueiro-da-India". The tea from the husk fiber is widely used to several inflammatory disorders. Crude extract and fractions obtained from Cocos nucifera "common variety" were evaluated to test the anti-inflammatory and antinociceptive activities.. Crude extract (CE, 50, 100, and 150 mg/kg), fraction 1 (F1, molecular weight lesser than 1 kDa, 1, 10, and 50mg/kg), fraction 2 (F2, molecular weight higher than 1 kDa, 1, 10, and 50mg/kg), and the references drugs morphine (5mg/kg), acetilsalicilic acid (200mg/kg), prometazine (30 mg/kg), and metisergide (5mg/kg) were evaluated on models of analgesia and inflammation.. CE, F1, and F2 significantly develop peripheral and central antinociceptive activity but with less effect on supra-spinal regions of the brain. Administration of the opioid antagonist, naloxone (5mg/kg) inhibited the antinociceptive effect indicating that Cocos nucifera crude extract and fractions may be acting in opioid receptors. CE and F1 also inhibited rat paw edema induced by histamine, and serotonin.. results demonstrated that Cocos nucifera and its fractions have antinociceptive and anti-inflammatory activities which confirm the popular use of this plant in several inflammatory disorders.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Cocos; Edema; Fruit; Male; Mice; Naloxone; Narcotic Antagonists; Pain; Phytotherapy; Plant Extracts

Trigonopleura malayana L. (Euphorbiaceae) resin, locally known as Gambir Sarawak, has been used traditionally to alleviate pain associated with insect bites, muscle ache, toothache and minor injuries. The present study was carried out using various animal models to determine the antinociceptive and antiinflammatory activities of the T. malayana resin aqueous extract. Antinociceptive activity was measured using the abdominal constriction, hot plate and formalin tests, while antiinflammatory activity was measured using the carrageenan-induced paw edema test. The extract, obtained after 24 h of soaking the dried resin in distilled water, was prepared in doses of 0.3, 3 and 10 mg/kg and administered subcutaneously 30 min prior to the assays. The mechanism of action was also determined by prechallenging with naloxone (10 mg/kg), a nonselective opioid antagonist. The extract was found to exhibit significant (P < 0.05) and dose-dependent antinociceptive and antiinflammatory activities; naloxone failed to inhibit the former activity. In conclusion, the aqueous extract of T. malayana resin possesses nonopioid antinociceptive and antiinflammatory activities, thus supporting previous claims regarding its traditional use by the Malays to treat various ailments, particularly those related to pain.

Topics: Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Edema; Euphorbiaceae; Injections, Subcutaneous; Lethal Dose 50; Male; Mice; Mice, Inbred BALB C; Models, Animal; Naloxone; Narcotic Antagonists; Pain; Pain Measurement; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Resins, Plant

The analgesic and antiinflammatory properties of mollic acid glucoside (MAG), a 1 alpha-hydroxycycloartenoid extract from Combretum molle leaf, have been investigated in mice and rats. The effects of graded doses of mollic acid glucoside (MAG, 5-80 mg/kg i.p.) were examined against thermally- and chemically-induced nociceptive pain in mice. Furthermore, the effects of graded doses of the plant extract (MAG, 5-80 mg/kg p.o.) were also investigated on rat paw oedema induced by subplantar injections of fresh egg albumin (0.5 mg/kg). Morphine (MPN, 10 mg/kg i.p.) and diclofenac (DIC, 100 mg/kg i.p.) were used as reference analgesic and antiinflammatory agents for comparison, respectively. Like DIC (100 mg/kg i.p.) and MPN (10 mg/kg i.p.), MAG (5-80 mg/kg i.p.) produced dose-dependent, significant (p < 0.05-0.001) analgesic effects against thermally and chemically induced nociceptive pain in mice. The extractive (MAG, 5-80 mg/kg i.p.) also significantly reduced (p < 0.05-0.001) rat paw oedema induced by subplantar injections of fresh egg albumin in a dose-related fashion. However, the extract (MAG, 5-80 mg/kg i.p.) was found to be less potent than diclofenac (DIC) as an analgesic or antiinflammatory agent. Experimental evidence obtained from this laboratory animal study indicates that the Combretum molle leaf extractive (MAG) possesses analgesic and antiinflammatory properties, and thus lend pharmacological credence to the folkloric, ethnomedical uses of the plant's leaf in the management, control and/or treatment of painful, arthritic and other inflammatory conditions in some rural communities of southern Africa.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Combretum; Diclofenac; Edema; Female; Hindlimb; Male; Mice; Mice, Inbred BALB C; Molecular Structure; Morphine; Naloxone; Pain; Pain Measurement; Phytotherapy; Plant Extracts; Plant Leaves; Rats; Rats, Wistar; Saponins

Morphine can inhibit inflammatory edema in experimental animals. The mechanisms and sites by which opioids exert this effect are still under debate. Since the spinal level is a site for modulation of the neurogenic component of inflammation, we investigated the effect of intrathecal (i.t.) administration of morphine, and the involvement of spinal nitric oxide (NO)/cyclic-guanosine monophosphate-GMP pathway in carrageenan (CG)-induced paw edema.. Male Wistar rats received i.t. injections of drugs (20 microL) 30 min before paw stimulation with CG (150 microg). Edema was measured as paw volume increase (mL), and neutrophil migration was evaluated indirectly by myeloperoxidase (MPO) assay.. Morphine (37, 75, and 150 nmol) inhibited inflammatory edema, but had no effect on MPO activity. Coinjection with naloxone (64 nmol) reversed the effect of morphine. The corticosteroid synthesis inhibitor, aminoglutethimide (50 mg/kg, v.o.), administered 90 min before morphine injection did not modify its antiedematogenic effect. Low doses of the NO synthase inhibitor, N(omega)-nitro-L-arginine (L-NNA; 10 and 30 pmol) increased, while higher doses (3 and 30 nmol) inhibited edema. The guanylate cyclase inhibitor 1H-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 21 and 42 nmol) increased, while the phosphodiesterase type 5 inhibitor sildenafil (0.15 and 1.5 nmol) inhibited paw edema. Coadministration of a subeffective dose of L-NNA (3 pmol) or ODQ (10 nmol) with morphine prevented its antiedematogenic effect, but sildenafil (0.15 nmol) rendered a subeffective dose of morphine effective (18 nmol). ODQ also prevented the antiedematogenic effect of the NO donor S-nitroso-N-acetyl-penicilamine.. These results support the idea that morphine can act on opioid receptors at the spinal level to produce antiedematogenic, and that the NO/cGMP pathway seems to be an important mediator in this effect.

Topics: Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Cyclic GMP; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Enzyme Inhibitors; Guanylate Cyclase; Inflammation; Injections, Spinal; Male; Morphine; Naloxone; Narcotic Antagonists; Neutrophil Infiltration; Neutrophils; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Nitroarginine; Oxadiazoles; Peroxidase; Phosphodiesterase Inhibitors; Piperazines; Purines; Quinoxalines; Rats; Rats, Wistar; S-Nitroso-N-Acetylpenicillamine; Signal Transduction; Sildenafil Citrate; Spinal Cord; Sulfones; Time Factors

This study was performed to determine the antinociceptive and anti-inflammatory activities of aqueous extract of Kaempferia galanga leaves using various animal models. The extract, in the doses of 30, 100, and 300 mg/kg, was prepared by soaking (1:10; w/v) the air-dried powdered leaves (40 g) in distilled water (dH(2)O) for 72 h and administered subcutaneously in mice/rats 30 min prior to the tests. The extract exhibited significant (P < 0.05) antinociceptive activity when assessed using the abdominal constriction, hot-plate and formalin tests, with activity observed in all tests occurring in a dose-dependent manner. Furthermore, the antinociceptive activity of K. galanga extract was significantly (P < 0.05) reversed when prechallenged with 10 mg/kg naloxone. The extract also produced a significantly (P < 0.05) dose-dependent anti-inflammatory activity when assessed using the carrageenan-induced paw-edema test. In conclusion, this study demonstrated that K. galanga leaves possessed antinociceptive and anti-inflammatory activities and thus supports the Malay's traditional uses of the plant for treatments of mouth ulcer, headache, sore throat, etc.

Topics: Analgesics, Non-Narcotic; Analysis of Variance; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Female; Mice; Mice, Inbred BALB C; Naloxone; Narcotic Antagonists; Pain; Pain Measurement; Phytotherapy; Plant Extracts; Plant Leaves; Rats; Rats, Sprague-Dawley; Zingiberaceae

1 The milky white latex of the plant Calotropis procera induces inflammatory response upon accidental exposure and on local administration that could be effectively ameliorated by antihistaminic and standard anti-inflammatory drugs. 2 The aim of the present study was to evaluate the anti-oedematogenic and analgesic effect of the bradykinin antagonist, bradyzide (BDZ) and the opioidergic analgesic, morphine (Mor) against inflammatory hyperalgesia induced by the dried latex (DL) of C. procera in the rat paw oedema model. 3 An aqueous solution of DL (0.1 ml of 1% solution) was injected into the sub-plantar surface of the rat paw and the paw volume was measured at different time intervals. The inhibitory effect of bradyzide and morphine on oedema formation and hyperalgesic response was compared with that of cyproheptadine (CPH), a potent inhibitor of DL-induced oedema formation. 4 The hyperalgesic response was evaluated by the dorsal flexion pain test, compression test and by observing motility, stair-climbing ability, and the grooming behaviour of the rats. 5 The effect of these drugs was also evaluated against DL-induced writhings in the mouse model. 6 Both bradyzide and morphine inhibited DL-induced oedema formation by 30-40% and CPH was more effective in this regard (81% inhibition). The antihyperalgesic effect of both the drugs was more pronounced than that of CPH. Both bradyzide and morphine markedly inhibited the grooming behaviour and the effect of morphine could be reversed by pretreatment with naloxone. 7 Thus, our study shows that DL-induced oedema formation is effectively inhibited by antihistaminic/antiserotonergic drug and associated hyperalgesia by analgesic drugs.

Topics: Analgesics, Opioid; Animals; Behavior, Animal; Bradykinin Receptor Antagonists; Calotropis; Cyproheptadine; Edema; Grooming; Hindlimb; Hyperalgesia; Inflammation; Latex; Male; Mice; Morphine; Motor Activity; Naloxone; Pyrrolidines; Rats; Rats, Wistar; Shivering; Thiosemicarbazones

Role of excitatory amino acids, glutamate, aspartate, and inhibitory amino acids, gamma aminobutyric acid (GABA) and glycine in brain damage caused by heat stress was examined in a rat model. Subjection of rats to 4 h heat stress at 38 degrees C in a biological oxygen demand (BOD) incubator resulted in a marked increase in glutamate and aspartate in some brain regions, whereas a significant decline in GABA and glycine was observed in several brain areas. Profound behavioural alterations and impairment of motor and cognitive functions were seen at this time. Breakdown of the blood-brain barrier (BBB), reduction in regional cerebral blood flow (CBF), edema formation and cell injuries are prominent in several parts of the brain. Pretreatment with multiple opioid receptor antagonist, naloxone (10 mg/kg, i.p.) significantly restored the heat stress induced decline in GABA and glycine and thwarted the elevation of glutamate and aspartate in various brain areas. The motor or cognitive deficits were also attenuated. A significant reduction in BBB permeability, cerebral blood flow abnormalities, edema formation and cell injuries was evident. These novel observations suggest that (i) glutamate, aspartate, GABA and glycine are involved in the pathophysiology of heat stress, and (ii) a balance between excitatory and inhibitory amino acids in brain is crucial in hyperthermia induced brain injuries or repair.

Topics: Animals; Aspartic Acid; Behavior, Animal; Blood-Brain Barrier; Brain; Capillary Permeability; Cerebrovascular Circulation; Cognition; Edema; Excitatory Amino Acids; gamma-Aminobutyric Acid; Glutamic Acid; Glycine; Hyperthermia, Induced; Image Processing, Computer-Assisted; Male; Microscopy, Electron, Transmission; Motor Activity; Naloxone; Narcotic Antagonists; Neurotransmitter Agents; Rats; Rats, Wistar

The diterpene, 12-acetoxyhawtriwaic acid lactone (AHAL, tanabalin) isolated from the flower buds of Egletes viscosa Less. (Asteraceae) was evaluated on capsaicin-induced ear edema and hindpaw nociception in mice. AHAL (12.5, 25 and 50 mg/kg, P. O.) significantly attenuated the ear edema response to topically applied capsaicin (250 microg), in a dose-related manner. At similar doses, AHAL also suppressed the nocifensive paw-licking behavior induced by intraplantar injection of capsaicin (1.6 microg). These responses to capsaicin were also greatly inhibited by ruthenium red (3 mg/kg, S. C.), a non-competitive capsaicin receptor (TRPV1) antagonist. The anti-edema effect of AHAL (50 mg/kg) seems unrelated to either blockade of mast cell degranulation or to histamine and serotonin receptor antagonism since AHAL did not modify the paw edema response induced by intraplantar injections of compound 48/80, histamine or serotonin. However, the hindpaw edema induced by substance P and vascular permeability increase induced by intraperitoneal acetic acid were significantly suppressed by AHAL. The antinociceptive effect of AHAL (50 mg/kg) was unaffected by naloxone pretreatment but was significantly antagonized by theophylline and glibenclamide, the respective blockers of adenosine and K(ATP)-channels. AHAL (50 mg/kg, P. O.) did not impair the ambulation or motor coordination of mice in open-field and rota-rod tests. These data suggest that AHAL inhibits acute neurogenic inflammation possibly involving capsaicin-sensitive TRPV1-receptors, endogenous adenosine and ATP-sensitive potassium channels.

Topics: Analgesics; Animals; Asteraceae; Capsaicin; Diterpenes; Diterpenes, Clerodane; Ear; Edema; Flowers; Glyburide; Hindlimb; Lactones; Male; Mice; Naloxone; Nociceptors; Substance P; Theophylline; TRPV Cation Channels

This study examined the effects of intracerebroventricular (i.c.v.), intraperitoneal (i.p.) or intraplantar (i.pl.) administration of ghrelin, the endogenous ligand of the growth hormone secretagogue receptor, in the development of hyperalgesia and edema induced by intraplantar injection of carrageenan in rats. Central ghrelin (4 ng to 4 microg/rat) given 5 min before carrageenan produced a dose-related reversal of carrageenan-induced mechanical hyperalgesia measured by Randall-Selitto test with an ED50 of 81.7 ng/rat. Ghrelin at the dose of 4 microg/rat i.c.v. was also effective in inhibiting edema. When ghrelin (4 microg/rat i.c.v.) was administered 150 min after carrageenan, it failed to modify either hyperalgesia or the paw volume. Given i.p., 30 min before carrageenan, ghrelin (20-160 microg/kg) induced a significant dose-dependent inhibition of hyperalgesia with an ED50 of 77 microg/kg and a slight reduction of edema. Intraplantar ghrelin (40 ng to 12 microg/rat) did not significantly modify both the hyperalgesic and edematous activities of carrageenan. The anti-hyperalgesic and anti-edematous effects of ghrelin (4 microg/rat i.c.v.) were reversed by naloxone (10 microg/rat i.c.v.). Systemic administration of the peripheral selective opioid antagonist, naloxone methiodide (3 mg/kg s.c.), did not antagonize antinociception elicited by i.p. ghrelin. Overall these data indicate that ghrelin exerts an inhibitory role on inflammatory pain through an interaction with the central opioid system.

Topics: Analysis of Variance; Animals; Behavior, Animal; Carrageenan; Cytokines; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Interactions; Edema; Gene Expression Regulation; Ghrelin; Male; Naloxone; Narcotic Antagonists; Pain; Pain Measurement; Pain Threshold; Peptide Hormones; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors

The aim of this study was to evaluate the analgesic effect of the low level laser therapy (LLLT) with a He-Ne laser on acute inflammatory pain, verifying the contribution of the peripheral opioid receptors and the action of LLLT on the hyperalgesia produced by the release of hyperalgesic mediators of inflammation.. All analgesic drugs have undesired effects. Because of that, other therapies are being investigated for treatment of the inflammatory pain. Among those, LLLT seems to be very promising.. Male Wistar rats were used. Three complementary experiments were done. (1) The inflammatory reaction was induced by the injection of carrageenin into one of the hind paws. Pain threshold and volume increase of the edema were measured by a pressure gauge and plethysmography, respectively. (2) The involvement of peripheral opioid receptors on the analgesic effect of the laser was evaluated by simultaneous injection of carrageenin and naloxone into one hind paw. (3) Hyperalgesia was induced by injecting PGE2 for the study of the effect of the laser on the sensitization increase of nociceptors. A He-Ne laser (632.8 nm) of 2.5 J/cm2 was used for irradiation.. We found that He-Ne stimulation increased the pain threshold by a factor between 68% and 95% depending on the injected drug. We also observed a 54% reduction on the volume increase of the edema when it was irradiated.. He-Ne LLLT inhibits the sensitization increase of nociceptors on the inflammatory process. The analgesic effect seems to involve hyperalgesic mediators instead of peripheral opioid receptors.

Topics: Animals; Carrageenan; Dinoprostone; Edema; Hyperalgesia; Inflammation; Injections; Low-Level Light Therapy; Male; Naloxone; Narcotic Antagonists; Nociceptors; Pain; Pain Threshold; Rats; Rats, Wistar

The EO of Ocimum micranthum was studied for a possible analgesic effect on the acetic acid induced writhing and formalin test in mice and antioedema activities on the carrageenan and dextran induced paw oedema in rats. The EO demonstrated antinociceptive effects, and pretreatment with naloxone did not reverse the antinociception, indicating that the opioid system is not involved. On the other hand, pretreatment with L-arginine (L-arg) reversed the antinociception, suggesting involvement of the nitric oxide (NO) system. The EO did not present an antioedematogenic effect in the carrageenan and dextran models.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Arginine; Brazil; Edema; Female; Male; Mice; Naloxone; Narcotic Antagonists; Ocimum; Oils, Volatile; Phytotherapy; Plant Oils

Recent studies suggest that peripheral morphine may represent a valuable treatment in acute inflammatory painful diseases through peripheral or central mechanisms. In the present study, anti-inflammatory effects of systemic morphine on carrageenan-induced hind paw oedema were examined in a model of peripheral acute oedema in mice. Carrageenan induced a time-dependent inflammation that was maximal 3 h after administration. While intraperitoneal administration of morphine sulfate at a low dose (1 mg/kg) increased carrageenan-induced hind paw oedema, intraperitoneal injection of morphine sulfate at a high dose (7 mg/kg) resulted in significant anti-inflammatory effects on carrageenan-induced hind paw oedema. These anti-inflammatory effects were blocked by pretreatment with naloxone. Measuring the serum levels of interleukin-1beta revealed that increases in serum levels of this cytokine were involved in morphine anti-inflammatory effects. Pretreatment with naloxone decreased interleukin-1beta serum levels near to those of control group. In conclusion, these data demonstrate that morphine produced pro- or anti-inflammatory effects in a dose-dependent manner through peripheral or central mechanisms. The observed anti-inflammatory effects may be due to an increase in the cytokine production and/or release by host immune systems.

Topics: Analgesics, Opioid; Animals; Anti-Inflammatory Agents; Carrageenan; Disease Models, Animal; Edema; Hindlimb; Inflammation; Interleukin-1; Male; Mice; Morphine; Naloxone; Narcotic Antagonists

Neuroimmune interactions control pain through activation of opioid receptors on sensory nerves by immune-derived opioid peptides. Here we evaluate mechanisms of intrinsic pain inhibition at different stages of Freund's adjuvant-induced inflammation of the rat paw. We use immunohistochemistry and paw pressure testing. Our data show that in early (6 h) inflammation leukocyte-derived beta-endorphin, met-enkephalin and dynorphin A activate peripheral mu-, delta- and kappa-receptors to inhibit nociception. In addition, central opioid mechanisms seem to contribute significantly to this effect. At later stages (4 days), antinociception is exclusively produced by leukocyte-derived beta-endorphin acting at peripheral mu and delta receptors. Corticotropin-releasing hormone (CRH) is an endogenous trigger of these effects at both stages. These findings indicate that peripheral opioid mechanisms of pain inhibition gain functional relevance with the chronicity of inflammation.

Topics: Animals; Corticotropin-Releasing Hormone; Dynorphins; Edema; Endorphins; Enkephalin, Methionine; Freund's Adjuvant; Hindlimb; Inflammation; Injections, Subcutaneous; Leukocytes; Male; Naloxone; Pain; Pain Threshold; Rats; Rats, Wistar; Stress, Physiological; Time Factors

It is believed that acupunctural stimulation induces an analgesic response mainly through a central mechanism: that is, through an increase in the production of opioid peptides and their release at different levels in the nervous system. We sought to establish whether the modulating effect of acupuncture on experimental neurogenic edema can be attributed to a central mechanism only or whether a peripheral mechanism could also exist. Intraperitoneal administration was compared to local administration in the same paw in rats that were injected with capsaicin and in the same dermatome of the acupunctural stimulation.. Experimentation was conducted on 105 male Sprague-Dawley rats weighing 180-220 g, divided into 7 groups as follows: group 1, control; groups 2-4 (15 animals), stimulated with manual acupuncture; group 3 also treated with intraperitoneal naloxone 1 mg/kg; group 4 also treated locally with naloxone (20 microg); groups 5-7 (15 animals), stimulated with 5 Hz and 5 mA electroacupuncture (EAP); group 6 also treated with intraperitoneal naloxone, 1 mg/kg, group 7 also treated locally with naloxone (20 microg).. The results indicate that the administration of 1 mg/kg of naloxone intraperitoneally can inhibit the modulating effect of acupunctural stimulation. Equally effective in inhibiting the modulating effect of acupunctural stimulation, although not having a systemic effect, is a 20-microg dose of naloxone administered peripherally on the site of edema induction.. It is possible to conclude that both systemic and peripheral mechanisms seem to be implicated in the modulating effect of acupuncture on the neurogenic inflammation mechanism.

Topics: Animals; Capsaicin; Edema; Electroacupuncture; Injections, Intraperitoneal; Injections, Subcutaneous; Male; Naloxone; Narcotic Antagonists; Neurogenic Inflammation; Random Allocation; Rats; Rats, Sprague-Dawley; Single-Blind Method

The effect of intraplantarly (i.pl.)-injected methionine-enkephalin (ME) on Concanavalin A (Con A)-induced paw edema in Dark Agouti (DA) and Albino Oxford (AO) rats was investigated. ME suppressed edema in DA rats, which was antagonized with naloxone (non-selective opioid receptor antagonist) and naltrindole (delta opioid receptors antagonist). Potentiating effect of ME in AO rats was blocked by naloxone, nor-binaltorphimine (kappa opioid receptors antagonist) and beta-funaltrexamine (mu opioid receptors antagonist). Dexamethasone suppressed edema in both rat strains. These findings suggest that strain-dependent differences in the effects of ME on inflammation in DA and AO rats could be related to diversity in opioid receptors expression in these strains.

Topics: Animals; Dexamethasone; Dose-Response Relationship, Drug; Edema; Enkephalin, Methionine; Glucocorticoids; Inflammation; Kinetics; Male; Naloxone; Naltrexone; Narcotic Antagonists; Rats; Species Specificity; Time Factors

Antinociceptive and anti-inflammatory effects and acute toxicity of aqueous infusion and ethanolic maceration extracts of the aerial parts of Zhumeria majdae were studied in mice and rats. Antinociceptive activity was determined using hot-plate and writhing tests. The effect of the extracts against acute inflammation was studied by acetic acid increased vascular permeability and xylene-induced ear edema in mice. The activity of the extracts against chronic inflammation was assessed using the cotton pellet test in rats. LD50 values of the infusion and maceration extracts were 3.09 g/kg body wt., and 3.94 g/kg body wt., respectively. Phytochemical screening of the extracts indicated the presence of flavonoids and tannins. In the hot-plate test, the intraperitoneal injection of both extracts showed significant and dose-dependent antinociceptive activity in mice. Naloxone, an opioid antagonist, on pretreatment inhibited the antinociceptive activity of the extracts. The extracts exhibited antinociceptive activity against acetic acid-induced writhing, which was partially blocked by naloxone. Both extracts showed significant effect against acute inflammation induced by acetic acid in mice. In the chronic inflammation test, efficacy of the extracts was similar to that of baclofen and dexamethasone in rats. It is concluded that the aqueous infusion and ethanolic maceration extract of the aerial parts of Zhumeria majdae have antinociceptive effects and this may be mediated by opioid receptors. The extracts also showed anti-inflammatory effects against acute and chronic inflammation.

Topics: Acetic Acid; Analgesics; Analgesics, Opioid; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Chromatography, High Pressure Liquid; Dexamethasone; Diclofenac; Edema; Female; Inflammation; Lamiaceae; Lethal Dose 50; Male; Mice; Morphine; Naloxone; Narcotic Antagonists; Pain; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Spectrum Analysis; Toxicity Tests, Acute; Xylenes

This study investigated the protective effects of ischemic preconditioning on intestinal ischemic injury and the role of endogenous opioid peptides (EOP) in these effects. Ischemia-reperfusion (I/R) induced by 30-min of ischemia and 60-min of reperfusion significantly increased the levels of malondialdehyde (MDA) and lactate dehydrogenase (LDH) and resulted in serious intestinal edema (wet weight/dry weight). The ischemic preconditioning (PC) elicited by three 8-min occlusion periods interspersed with 10-min reperfusion markedly attenuated intestinal injury caused by ischemia-reperfusion. Pretreatment with morphine (300 microg x kg(-1), i.v.) 10-min before ischemia and reperfusion mimicked the protection produced by PC. Naloxone (3 mg x kg(-1), i.v.) abolished the protection of morphine-induced preconditioning and ischemic preconditioning in rat intestine. However, there were no changes between naloxone alone and control groups. Treatment with naloxone before ischemia-reperfusion had no effect on animals compared with the I/R group. In addition, we also measured the content of endogenous opioid peptides (Leu-enkephalin) in the effluent which was collected before and during preconditioning. It was shown that the release of leu-enkephalin was markedly increased during preconditioning. These results suggested that EOP might play an important role in PC in rat small intestine.

Topics: Analgesics, Opioid; Animals; Drug Interactions; Edema; Enkephalin, Leucine; Intestinal Diseases; Intestinal Mucosa; Intestine, Small; Ischemia; Ischemic Preconditioning; L-Lactate Dehydrogenase; Male; Malondialdehyde; Morphine; Naloxone; Narcotic Antagonists; Opioid Peptides; Rats; Rats, Wistar; Receptors, Opioid; Reperfusion Injury

The antinociceptive action of a novel pyrazole-derived compound, 3-methyl-5-hydroxy-5-trichloromethyl-1H-1-pyrazolcarboxyamide (MPCA) was evaluated using the formalin and tail-immersion tests in mice. Anti-inflammatory activity was assessed by paw plethysmometry in adult rats using the carrageenin-induced paw edema test. Subcutaneous administration of MPCA (22, 66, and 200 mg/kg) induced a dose-dependent decrease in the time spent licking during the neurogenic and inflammatory phases of the formalin test, and preadministration of naloxone (1 mg/kg, sc) did not prevent MPCA-induced (200 mg/kg, sc) antinociception. Naloxone decreased the spontaneous locomotor activity of mice, while MPCA had no effect on locomotion. In contrast, administration of the opioid antagonist caused a significant increase in the locomotor behavior of mice previously injected with MPCA. MPCA was devoid of antinociceptive action by the tail-immersion test and of anti-inflammatory activity. Moreover, MPCA had no effect on the motor performance of mice in the rotarod test. These results suggest that MPCA induces antinociception in the neurogenic and inflammatory phases of the formalin test, an effect that does not involve opioid receptors.

Topics: Analgesics; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Edema; Formaldehyde; Immersion; Male; Mice; Morphine; Naloxone; Narcotic Antagonists; Pain Measurement; Postural Balance; Pyrazoles; Rats; Rats, Wistar

The effect of some B vitamins in chemical and thermal models of nociception in mice was investigated. The association thiamine/pyridoxine/cyanocobalamin (TPC, 20-200 mg/kg, i.p. or per os), thiamine, pyridoxine (50-200 mg/kg, i.p.) or riboflavin (3-100 mg/kg, i.p) induced an antinociceptive effect, not changed by naloxone (10 mg/kg, i.p.), in the acetic acid writhing model. Treatment for 7 days with thiamine/pyridoxine/cyanocobalamin (100 or 200 mg/kg, i.p.), thiamine (50 or 100 mg/kg) or pyridoxine (50 or 100 mg/kg) or acute treatment with riboflavin (6 or 12 mg/kg, i.p) inhibited the nociceptive response induced by formaldehyde. The B vitamins did not inhibit the nociceptive response in the hot-plate model. Both 7-day thiamine/pyridoxine/cyanocobalamin (100 mg/kg, i.p.) or acute riboflavin (25 or 50 mg/kg, i.p.) treatment partially reduced formaldehyde-induced hindpaw oedema. The B vitamins antinociceptive effect may involve inhibition of the synthesis and/or action of inflammatory mediators since it was not observed in the hot-plate model, was not reversed by naloxone, only the second phase of the formaldehyde-induced nociceptive response was inhibited, and formaldehyde-induced hindpaw oedema was reduced.

Topics: Acetic Acid; Animals; Constriction; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Formaldehyde; Hindlimb; Injections, Intraperitoneal; Injections, Subcutaneous; Male; Mice; Motor Activity; Naloxone; Nociceptors; Pain; Pain Measurement; Pyridoxine; Riboflavin; Thiamine; Vitamin B 12; Vitamin B Complex

We evaluated the anti-edema/antinociceptive effects of subcutaneous free and liposomal morphine in rats with carrageenan-induced inflammation of the paw. We assessed antinociception by the paw pressure test and edema by plethysmography. Unilamellar liposomes (150-200 nm) with 0.3% morphine hydrochloride were used; encapsulation significantly reduced the rate for release of morphine in vitro. During inflammation, the antinociceptive potency of free, but not liposomal morphine increased 2.5 times; moreover, duration of the effects was prolonged by encapsulation (p < 0.001). The anti-edema effects of liposomal morphine were more pronounced (p < 0. 001) and of longer duration (p < 0.05). All the effects were reversed by naloxone. The results show that morphine encapsulation enhances the anti-edema effects and prolongs antinociception.

Topics: Analgesics, Opioid; Animals; Carrageenan; Drug Carriers; Edema; Liposomes; Male; Morphine; Naloxone; Narcotic Antagonists; Pain Measurement; Rats; Rats, Sprague-Dawley

The pharmacological activity of phenylacetyl-Phe-Ser-Arg-N-(2, 4-dinitrophenyl)-ethylenediamine (TKI), a tissue kallikrein specific inhibitor, was assessed using models of nociception and inflammation in mice. Injection of TKI (13.6 - 136 micromol kg(-1), i.p. or 41 - 410 micromol kg(-1), s.c.) produced a dose-related inhibition of the acetic acid-induced writhes (by 37 to 85% or 34 to 80%, respectively). The antinociceptive activity of TKI (41 micromol kg(-1), i.p.) was maximal after 30 min injection and lasted for 120 min. The effect was unaltered by pretreatment with naloxone (8.2 micromol kg(-1), s.c.) or bilateral adrenalectomy. TKI (41 and 136 micromol kg(-1), i.p.) produced a dose-related decrease of the late phase of formalin-induced nociception by 79 and 98%, respectively. At 136 micromol kg(-1), i.p., TKI also shortened the duration of paw licking in the early phase by 69%. TKI (41 and 136 micromol kg(-1), i.p.) also reduced the capsaicin-induced nociceptive response (by 51 to 79%). TKI (41 micromol kg(-1), i.p. or 410 micromol kg(-1), s.c.) reduced the oedematogenic response, from the second to the fifth hour after carrageenin injection by 36 to 30% or by 47 to 39%, respectively. Pretreatment with TKI (41 micromol kg(-1), i.p.) reduced the capsaicin-induced neurogenic inflammation in the mouse ear by 54%. It is concluded that TKI presents antinociceptive and antiinflammatory activities mediated by inhibition of kinin formation by tissue kallikrein in mice. The results also indicate that the tissue kallikrein-dependent pathway contributes to kinin generation in nociceptive and inflammatory processes in mice.

Topics: Adrenalectomy; Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Edema; Enzyme Inhibitors; Female; Inflammation; Kinins; Male; Mice; Naloxone; Oligopeptides; Pain; Peritonitis; Tissue Kallikreins

The decoction or juice of leaves of Boerhaavia diffusa L. (Nyctaginaceae) is used in Martinican folk medicine for its analgesic and anti-inflammatory properties. In the present investigation we studied the acute oral (p.o.) toxicity of a crude extract obtained from a lyophilized decoction (DE) and from the juice (JE) of fresh leaves. We observed no signs of toxicity up to the dose of 5000 mg/kg (p.o.) in mice. At the dose of 1000 mg/kg, neither extract altered sleeping time evoked by the administration of pentobarbital sodium (i.p.). The DE and JE of B. diffusa were assessed in standard rodent models of algesia and inflammation. We investigated the antinociceptive effect of DE and JE in chemical (acetic acid) and thermal (hot plate) models of hyperalgesia in mice. Dipyrone sodium (200 mg/kg), JE (1000 mg/kg) and DE at the same dose (p.o.), produced a significant inhibition of acetic acid-induced abdominal writhing in mice (100, 50 and 47% inhibition, respectively) when compared with the negative control (P<0.001). In the hot-plate test in mice, morphine and JE produced a significant increase in latency during the observation time. The DE, however, only raised the pain thresholds during the first period (30 min) of observation (P<0.05). The extracts of B. diffusa were also investigated for their anti-edematogenic effect on carrageenan-induced edema in mice. However, neither extract inhibited the paw edema induced in mice (P>0.05). In the acetic acid-induced abdominal writhing in mice, pre-treatment of the animals with naloxone (5 mg/kg, i.p.) significantly reversed the analgesic effect of morphine and JE but not that of DE. These data show that the active antinociceptive principle of B. diffusa is present mainly in the juice of fresh leaves and has a significant antinociceptive effect when assessed in these pain models. The mechanism underlying this analgesic effect of fresh leaves of B. diffusa remains unknown, but seems to be related to interaction with the opioid system.

Topics: Acetates; Analgesics, Non-Narcotic; Analgesics, Opioid; Animals; Carrageenan; Edema; Hot Temperature; Hypnotics and Sedatives; Lethal Dose 50; Male; Martinique; Mice; Morphine; Naloxone; Narcotic Antagonists; Pain; Pain Measurement; Pentobarbital; Plant Extracts; Plants, Medicinal; Reaction Time; Sleep

The synthesis of a new series of nonpeptide derivatives of interleukin-1 beta sequence is described. Compounds have been investigated for their relative activity regarding antinociception and suppression of inflammation. Several compounds with R1(R)Lys [CH2N]-Pro structure showed better efficacy in the inflamed paw pressure test than indometacin and morphine. In terms of the relative potencies the above mentioned products (i.e. compounds 2, 4, 5, 6; ED50 values of 0.002, 0.0035, 0.0032, 0.0074 mg/kg i.p. respectively) were 10-100 times more potent than indometacin and morphine (ED50 values of 0.22 and 0.75 mg/kg). Compounds 1-14 were not able to inhibit binding of labeled interleukin-1 beta to EL 4-6.1 murine cells, since they had no affinity for interleukin-1 beta receptors. The antinociceptive activity elicited by compound 4 in the rat inflamed paw pressure test was inhibited by naloxone, but the compound was inactive in the mouse hot plate and rat paw pressure tests. These results suggest that compound 4 exerts its antinociceptive activity through a mechanism which is based on the local release of endogenous opioids in injured tissue.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Cells, Cultured; Drug Tolerance; Edema; Inflammation; Interleukin-1; Magnetic Resonance Spectroscopy; Male; Mice; Models, Molecular; Naloxone; Narcotic Antagonists; Pain Measurement; Peptide Fragments; Proline; Rats; Rats, Wistar; Reaction Time; Receptors, Interleukin

Oral administration of the feverfew (Tanacetum parthenium) extract led to significant antinociceptive and anti-inflammatory effects against acetic acid-induced writhing in mice and carrageenan-induced paw edema in rats, respectively. These responses were dose-dependent (10, 20, 40 mg/kg, p.o.). Parthenolide (1, 2 mg/kg i.p.), the active constituent of the extract also produced antinociceptive and anti-inflammatory effects. Naloxone (1 mg/kg i.p.), an opiate antagonist, failed to reverse feverfew extract and parthenolide-induced antinociception. Feverfew extract in higher doses (40, 60 mg/kg p.o.) neither altered the locomotor activity nor potentiated the pentobarbitone-induced sleep time in mice. It also did not change the rectal temperature in rats. Feverfew extract exerted antinociceptive and anti-inflammatory effects without altering the normal behaviour of the animals.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Body Temperature; Carrageenan; Dose-Response Relationship, Drug; Drug Interactions; Edema; Female; Foot; Male; Mice; Motor Activity; Naloxone; Narcotic Antagonists; Plant Extracts; Plants, Medicinal; Rats; Sesquiterpenes; Sleep; Tanacetum parthenium; Time Factors

The present study was performed to explore the effects of intrathecal administration of calcitonin gene-related peptide8-37 (CGRP(8-37)) on the hindpaw withdrawal latency (HWL) to pressure in rats with one thermally injured hindpaw. Furthermore, the interaction of CGRP(8-37)and naloxone was studied. Thermal injury was performed by dipping the left paw into 60 degrees C for 20 s. This induced a significant increase in the volume of the left hindpaw (P<0.001) and significant bilateral decreases of the latency of hindpaw withdrawal response to mechanical stimulation (Left: P<0.001; right: P<0.05). Intrathecal administration of 10, 20 and 40 nmol of CGRP(8-37), but not of 1 or 5 nmol, induced a significant bilateral increase in HWLs (P<0.001). The effect of CGRP(8-37) was partly reversed by intrathecal injection of naloxone at a dose of 32 and 64 microg respectively. Using radioimmunoassay, we found a significant bilateral increase in the concentration of CGRP-like immunoreactivity in the perfusate of both hindpaws 24 h after unilateral thermal injury (left: P< 0.001; right: P< 0.05). There was also an increase in the amount of CGRP-like immunoreactivity in the cerebrospinal fluid (P< 0.001), but not in plasma. The results indicate that CGRP plays a role in the transmission of nociceptive information in the spinal cord of thermally injured rats. Furthermore, our findings suggest that opioids can modulate CGRP-related effects in the spinal cord.

Topics: Animals; Antibody Specificity; Burns; Calcitonin Gene-Related Peptide; Edema; Extracellular Space; Hot Temperature; Inflammation; Injections, Spinal; Male; Miotics; Naloxone; Narcotic Antagonists; Nociceptors; Pain; Peptide Fragments; Physical Stimulation; Pressure; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Reaction Time; Reflex; Spinal Cord

We have examined the effect of the micro-opioid analgesic buprenorphine on osteoclastic bone resorption in vitro and in the rat adjuvant arthritis model. In the bone slice assay buprenorphine inhibited osteoclastic bone resorption with an IC50 of 1 microM. This effect was not mimicked by the micro-opioid agonist ([D-Ala, N-Me-Phe, Gly-ol]-enkephalin and was not prevented by the micro-opioid antagonist naloxone. Since other agents that inhibit osteoclastic bone resorption, such as bisphosphonates and calcitonin prevent bone erosion in the rat adjuvant arthritis model, we also examined the effect of buprenorphine in this model. Surprisingly, buprenorphine exacerbated inflammation measured by paw volume and increased joint destruction assessed by X-ray scores, in the injected paws and particularly in the non-injected paws. These studies also show that attempts to ameliorate animal suffering in this chronic model by using centrally acting analgesics such as buprenorphine may lead to complications in interpreting screening results obtained with novel, potential anti-arthritic compounds.

Topics: Analgesics; Analgesics, Opioid; Animals; Arthritis, Experimental; Arthrography; Bone Resorption; Buprenorphine; Cells, Cultured; Disease Models, Animal; Edema; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalins; Femur; Lethal Dose 50; Naloxone; Narcotic Antagonists; Osteoclasts; Rats

Topics: Animals; Edema; Enkephalins; Evoked Potentials; Inflammation; Mustard Plant; Naloxone; Nerve Fibers; Neurons, Afferent; Neuropeptides; Neurotransmitter Agents; Paraffin; Plant Extracts; Plant Oils; Plants, Medicinal; Rats; Skin

The possibility that opioid peptides participate in alteration of spinal cord conduction following trauma to the cord was investigated in a rat model using a pharmacological approach. Spinal cord injury was produced in urethane anesthetized animals by a longitudinal incision into the right dorsal horn of T10-11 segments (2 mm deep and 5 mm long). Spinal cord evoked potentials (SCEP) were recorded epidurally from the T9 (rostral) and T12 (caudal) segments after stimulation of the ipsilateral tibial and sural nerves at the ankle. SCEP from both rostral and caudal segments consisted of a small positive peak followed by a high negative peak. Infliction of trauma in untreated rats resulted in an immediate depression of the rostral maximal negative peak (MNP) amplitude. This depression was long-lasting. Later, a significant increase in the latency of the rostral MNP amplitude occurred. Naloxone was administered in a high dosage (10 mg/kg, i.p.) to block mu-, delta- and kappa-opioid receptors 30 min before injury. This drug treatment inhibited the immediate post-injury decrease of the rostral MNP amplitude without any significant effect on latency changes. Measurement of water content in the traumatized spinal cord segment showed a significant reduction in the drug treated animals 5 h after trauma (71.46 +/- 0.54) as compared with untreated controls (74.65 +/- 0.76). However, 1 mg or 5 mg/kg dosages of the drug were not effective in reducing the SCEP changes or edema after injury. These results strongly suggest that blockade of kappa-opioid receptors with high doses of naloxone is important in reduction of trauma induced alteration of SCEP and edema formation in spinal cord injury.

Topics: Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Evoked Potentials; Male; Naloxone; Neural Conduction; Rats; Rats, Sprague-Dawley; Receptors, Opioid; Spinal Cord Injuries

Morphine has been shown to alter various aspects of the immune response. We examined its effect on progression of the T-cell-mediated model, rat adjuvant arthritis. Saline, morphine or the opioid antagonist naloxone were administered to male Wistar rats via subcutaneous osmotic pumps implanted three days prior to adjuvant disease induction by an intra-dermal injection of Mycobacterium tuberculosis in oil. The time of disease onset was found to be accelerated (day 11) for the morphine group as compared to the saline control (day 13). In addition morphine produced a significant increase in paw swelling (days 13 and 14), bone demineralization and bone erosions. A significant decrease in body weight as compared to the saline control was also observed. Naloxone had no significant effect on the degree of the inflammation seen, although like morphine it significantly increased bone demineralization and bone erosions as assessed by radiography.

Topics: Animals; Arthritis, Experimental; Edema; Infusion Pumps, Implantable; Male; Morphine; Naloxone; Rats; Rats, Wistar

The antinociceptive effect of the octapeptide vapreotide, an analog of somatostatin, was studied after systemic injection in normal mice using the hot plate and abdominal stretching assays, and in normal rats using the paw pressure analgesiometric assay. Vapreotide was ineffective at 1 microgram/kg s.c. in the hot plate test in mice, but 30 min after injection it induced an antinociceptive effect at s.c. injected doses of 8, 64, 512 and 4096 micrograms/kg, with an ED50 of 213 +/- 5 micrograms/kg. For the three highest doses this effect persisted 24 hr after the injection (maximal increase: +80 +/- 23% for 512 micrograms/kg) and disappeared at 48 hr. In the phenylbenzoquinone stretching test, in mice, the ED50 was 186 +/- 6 micrograms/kg (maximal decrease: -63 +/- 5%); the effect persisted 24 hr only for the same two highest doses. Using the paw pressure test, in rats, a dose-dependent increase in paw withdrawal and vocalization thresholds was observed for 21 and 24 hr, respectively, after s.c. injections of 16, 64 and 512 micrograms/kg. Global scores obtained for vocalization thresholds were significantly increased (vs. paw withdrawal thresholds) for 64 and 512 micrograms/kg. Carrageenan-induced nociception in rats was reduced for 21 hr by 64 and 512 micrograms/kg s.c.; scores of the contralateral noninflamed paw were also increased. Vapreotide administered locally in the inflamed paw was inactive. No change in edema volume was obtained after systemic injection of vapreotide.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amino Acid Sequence; Analgesics; Animals; Brain; Disease Models, Animal; Edema; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalins; In Vitro Techniques; Inflammation; Male; Membranes; Mice; Molecular Sequence Data; Morphine; Motor Activity; Naloxone; Necrosis; Nociceptors; Octreotide; Pain Measurement; Rats; Rats, Sprague-Dawley; Somatostatin; Spinal Cord; Time Factors; Tritium

The influence of naloxone (an opioid receptor antagonist) on spinal cord conduction and edema formation as a result of trauma to the cord was investigated in a rat model. The spinal cord injury (SCI) was inflicted in urethane anesthetized animals by a longitudinal incision into the right dorsal horn of the T10-11 segments, about 2 mm deep and 5 mm long. Spinal cord evoked potentials (SCEP) were recorded epidurally from the T9 (rostral) and T12 (caudal) segments after stimulation of the ipsilateral tibial and sural nerves at the ankle. The edema was measured by determining water content of the cord at s h after injury. In rats not given naloxone SCI resulted in an immediate long-lasting depression of the rostral maximal negative peak (MNP) amplitude (about 60%) and a significant increase in the latency of the rostral maximal positive peak (MPP). Pretreatment with naloxone inhibited the immediate post-injury decrease of the rostral MNP and some of the increase of MPP latency. The water content in the traumatized spinal cord was reduced by 3% in naloxone treated animals compared with untreated injured controls. Our results indicate that endogenous opioid peptides participate in changes of spinal cord conduction after trauma and influence edema formation probably via multiple opioid receptors.

Topics: Afferent Pathways; Animals; Edema; Electric Stimulation; Evoked Potentials; Ganglia, Spinal; Male; Naloxone; Opioid Peptides; Peripheral Nerves; Rats; Rats, Sprague-Dawley; Reaction Time; Spinal Cord Injuries; Synaptic Transmission

The effect of long-term continuous subcutaneous infusion of naloxone on blunt spinal cord injury in the rat was assessed using four tests of neurological function, seven histological categories, and two electrophysiological measures. All four neurological function tests showed a trend toward improvement in naloxone-treated animals: the degree of improvement was statistically significant in two of the four categories. A significant reduction in myelin sheath edema was found in the naloxone-treated animals. Although there was a decrease in corticomotor-evoked potentials complexity following injury, there was no significant difference in naloxone-treated animals. Somatosensory-evoked potentials were significantly increased in amplitude and latency in naloxone-treated animals. This increase was most apparent at 60 min: no difference was found by 3 weeks postinjury. These results confirm earlier reports that naloxone can ameliorate the functional neurological deficits of spinal cord injury. Naloxone also produces alterations in the somatosensory-evoked responses in the early phase of treatment and significantly reduces myelin sheath edema.

Topics: Animals; Arachnoid; Drug Evaluation, Preclinical; Edema; Evoked Potentials, Somatosensory; Myelin Sheath; Naloxone; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries; Wallerian Degeneration; Wounds, Nonpenetrating

Intracerebroventricularly (icv) administered met-enkephalin, leu-enkephalin, and morphine induced dose-related attenuation of carrageenin-induced acute paw oedema in rats. Naloxone (10 micrograms, icv) antagonized the anti-inflammatory effects of the enkephalins (20 micrograms) and morphine (20 micrograms), but itself induced an anti-inflammatory effect at a higher dose (50 micrograms, icv). The anti-inflammatory effects of the enkephalins, morphine, and the higher dose of naloxone were significantly inhibited by metyrapone, an inhibitor of endogenous corticoid synthesis. The icv-administered doses of the enkephalins and morphine induced insignificant inflammation-attenuating effects when administered i.p. Results suggest that the anti-inflammatory effects of the enkephalins and morphine are exerted through central opiate receptors. Furthermore, the inflammation-attenuating effects of these drugs and the higher dose of naloxone appear to be dependent upon endogenous corticoids, suggesting that activation of the hypothalamo-pituitary-adrenocortical axis may be involved.

Topics: Animals; Arthritis, Experimental; Brain; Carrageenan; Edema; Enkephalin, Leucine; Enkephalin, Methionine; Female; Hindlimb; Hypothalamo-Hypophyseal System; Injections, Intraperitoneal; Injections, Intraventricular; Male; Metyrapone; Morphine; Naloxone; Pituitary-Adrenal System; Rats; Rats, Wistar

This study examined the possible peripheral activity of eel calcitonin in the modulation of the response to noxious pressure on inflamed paws in rats (Randall and Selitto test). The intraplantar injection of eel calcitonin (20-200 ng/rat) but not the subcutaneous administration (200 ng and 2 micrograms/rat, s.c.), was able to significantly inhibit hyperalgesia induced by intraplantar injection of carrageenin. The development of oedema on the other hand was not inhibited. The intraplantar administration of eel calcitonin (200 ng/rat) in a non-inflamed paw did not modify paw pressure thresholds. Eel calcitonin (200 ng/rat, intraplantar, i.pl.) was also able to elicit an antinociceptive effect on formalin-induced hyperalgesia, both when the peptide was injected before or after (60 min) formalin. This effect, at difference with morphine (80 micrograms/rat, i.pl.), was not blocked by naloxone (10 micrograms/rat, i.pl.). These results demonstrate the local antinociceptive effect of eel calcitonin in inflammatory pain and might indicate a new way of using calcitonin in the control of pain.

Topics: Analgesics; Animals; Calcitonin; Carrageenan; Edema; Foot; Inflammation; Injections; Male; Naloxone; Rats; Rats, Inbred Strains

The effect of clomipramine (CMI), a tricyclic antidepressant, was studied on an acute inflammatory pain model in an attempt to understand its potential antinociceptive activity, the involvement of a central and/or peripheral component and its influence on the inflammatory process. When administered (i.v.) before the inflammatory agent, carrageenan (CAR), CMI (0.125, 0.25 and 0.5 mg/kg) completely prevented the development of the hyperalgesia for 70-120 min according to the doses. This antinociceptive effect was suppressed by naloxone (100 micrograms/kg i.v.) for 65 min. Neither higher doses (1, 2 and 20 mg/kg, i.v.) nor CMI injected into the inflamed paw (15 min before CAR) modified pain thresholds. Moreover, CMI (0.5 and 2 mg/kg, i.v.) administered 15 min before CAR markedly increased the volume of the CAR-induced oedema. These results (1) demonstrate an opioid-dependent antinociceptive effect of CMI on this model, the doses used being lower than those active in thermal or electrical tests, and (2) tend to exclude a peripheral mechanism and an NSAID-like anti-inflammatory activity suggested by previous in vitro studies.

Topics: Analgesics; Animals; Central Nervous System; Clomipramine; Edema; Foot; Injections; Injections, Intravenous; Male; Naloxone; Pain; Peripheral Nerves; Rats; Rats, Inbred Strains; Sensory Thresholds

The oedema produced in the mouse by intraplantar injection of the venom of Trimeresurus flavoviridis was inhibited by morphine (Mo) and by naloxone (Nx); the action of Mo increased with the dose, whereas that of Nx first progressed and thereafter regressed with the dose; very small doses of Nx antagonized Mo. Methylnaloxone (MeNx), a quaternary ammonium derivative of Nx was much less effective than Nx by the subcutaneous route but almost as effective by the intraplantar route. Peripheral opioidergic receptors are thus likely to be involved. Very high doses of Mo acted an synergistically with an optimal dose of EDTA or zymosan; complex interactions occurred between lower doses of Mo or Nx and EDTA or zymosan.

Topics: Animals; Crotalid Venoms; Dose-Response Relationship, Drug; Drug Interactions; Edema; Edetic Acid; Foot; Injections; Kinetics; Male; Mice; Morphine; Naloxone; Oxymorphone; Receptors, Opioid; Zymosan

Topics: Analgesia; Animals; Arthritis; Arthritis, Experimental; Carrageenan; Edema; Inflammation; Naloxone; Rats

Thermal injury to the skin increases transfer of plasma fluids and proteins into the interstitium. Here, protein extravasation and edema were produced by immersion of the anesthetized rat's paw in 48 degrees C or 58 degrees C water for 5 min. Protein extravasation was measured by Evans blue dye leakage into the skin and edema by increases in skin weights. Corticotropin-releasing factor (CRF), having the human/rat 41-amino acid sequence, was efficacious in reducing these indices of thermal injury. Injected i.v. at microgram doses or intradermally at nanogram doses, it inhibited the protein extravasation and edema produced by heat. The intradermal median inhibitory dose (ED50) of CRF against protein extravasation elicited by 48 degrees C water was 21.8 times lower than the i.v. ED50, indicating that CRF's actions occurred locally in the paw skin. Ovine-CRF and dynorphin A(1-13) injected i.v. inhibited the protein extravasation and edema induced by 58 degrees C water, but morphine, ethylketocyclazocine and FK 33,824 (a stabilized enkephalin analog) were not active at this temperature. CRF may be a powerful inhibitor of the acute inflammatory response of the skin to thermal irritation.

Topics: Animals; Blood Proteins; Burns; Capillary Permeability; Corticotropin-Releasing Hormone; Dose-Response Relationship, Drug; Edema; Male; Naloxone; Rats

The antidotal effects of antiinflammatory agents, inhibitors of bioamine syntheses, an opioid antagonist and other pharmacological agents on lethal toxicity, leukocytosis and ear inflammation, were investigated in mice subcutaneously administered or topically exposed to T-2 toxin, a trichothecene mycotoxin of Fusarium species. The acute lethal toxicity of T-2 toxin was reduced by administration of the steroidal anti-inflammatory agents, prednisolone and dexamethasone, and prolongation of survival times was demonstrated with an antihistaminic agent, diphenhydramine, and an opioid antagonist, naloxone. Prednisolone also antagonized leukocytosis and the increment of ear weight caused by T-2 toxin. These findings suggest that the action site(s) of steroidal anti-inflammatory agents is involved in the development of the toxic actions of T-2 toxin, and the implications of the results with bioamines and opioids are also discussed.

Topics: Animals; Anti-Inflammatory Agents; Antimetabolites; Dexamethasone; Edema; Lethal Dose 50; Leukocytosis; Male; Mice; Naloxone; Prednisolone; Sesquiterpenes; T-2 Toxin

In the rat, previous injection of turpentine reduced carrageenan-induced oedema. Naloxone and nalorphine did not modify the anti-inflammatory effect of this kind of counter-irritation. Morphine had no influence on carrageenan oedema. These results suggest that endogenous endorphins take no part to the anti-inflammatory effect of counter-irritation by turpentine.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Drug Interactions; Edema; Female; Irritants; Male; Nalorphine; Naloxone; Rats; Rats, Inbred Strains; Turpentine

Morphine inhibited the oedema formation induced by carrageenan. The anti-inflammatory activity developed 120 min after carrageenan injection, suggesting that inhibition of the kinin phase might be partly responsible. This assumption is supported by the findings that morphine inhibited bradykinin oedema but did not influence oedema formation induced by histamine, 5-HT or PGE2. The anti-inflammatory activity of morphine was partially inhibited by naloxone (0.5-1 mg kg-1) in the carrageenan oedema test. Zymosan-stimulated chemoluminescence of neutrophils of the rat was inhibited both by morphine (0.1-10 microM) and naloxone (1-100 microM). When morphine and naloxone were administered simultaneously (10 microM) their inhibitory effects were additive. Naloxone also failed to antagonize the inhibitory action of morphine in lower dose (0.1 microM). These results suggest that the effect of morphine in inflammation might be mediated either by one of the opiate receptor subtypes insensitive to naloxone or a non-opiate mechanism might be involved.

Topics: Animals; Carrageenan; Edema; Female; In Vitro Techniques; Indomethacin; Leukocytes; Luminescent Measurements; Male; Morphine; Naloxone; Rats; Receptors, Opioid; Zymosan

The antinociceptive properties of suprofen [alpha-methyl-4-(thienylcarbonyl)benzene acetic acid] are described in a pathologically induced hyperalgesic model, the rat adjuvant arthritis flexion test. By using this assay, suprofen was characterized as an orally effective, non-narcotic analgesic with a rapid onset and 4-hr duration of activity. Suprofen is 50 times more potent than acetaminophen, five times more potent than codeine and equipotent to the new peripheral analgesics, zomepirac and diflunisal. In combination experiments, suprofen potentiates the analgesic effects of acetaminophen and, unlike morphine, the analgesic effect of suprofen is not blocked by naloxone. In other hyperalgesic assays, suprofen is an extremely potent inhibitor of arachidonate-induced writhing and is equipotent to morphine in the yeast-induced paw edema (Randall-Selitto) assay. Additionally, suprofen is inactive on the normal paw in the Randall-Selitto test, the mouse Eddy hot-plate test and the tail withdrawal reflex assay induced by warm water in rats, all sensitive tests capable of detecting central (narcotic) but not peripheral analgesics. Activity on prostaglandin biosynthesis from several species and tissues suggests that suprofen is a tissue selective inhibitor of prostaglandin synthesis. These experiments suggest that suprofen represents a new class of potent, orally effective, peripheral (non-narcotic) analgesics with potential usefulness in a variety of clinical pain situations formerly reserved for narcotics.

Topics: Acetaminophen; Analgesics; Animals; Arachidonic Acids; Arthritis, Experimental; Biological Assay; Cattle; Dogs; Dose-Response Relationship, Drug; Drug Interactions; Edema; Epoprostenol; Female; Hyperalgesia; Kidney; Male; Naloxone; Oxygenases; Phenylpropionates; Prostaglandin Antagonists; Prostaglandins; Rabbits; Rats; Regional Blood Flow; Suprofen