Analgesic and neuromotor effects of two extracts of Zanthoxylum rhoifolium (Rutaceae) in the Swiss albino mouse (Mus musculus) / Efectos analgésicos y neuromotores de dos extractos de Zanthoxylum rhoifolium (Rutaceae) en el ratón albino suizo (Mus musculus)

Background: Colombia has a high diversity of medicinal plants, including Tachuelo (Zanthoxylum rhoifolium), a tree belonging to the family Rutaceae, which has been attributed an analgesic use by communities of the Colombian southwest. Nevertheless, this species has been scarce studied in Colombia. The studies have been limited to the isolation of compounds with antifungal and insecticide activity, using the leaves, branches, and bark of the plant in aqueous, and organic extracts. Neither pharmacological tests have been carried out, nor the analgesic and neuromotor activity have been tested from preparations with this plant's fruits. Objectives: To evaluate the analgesic and neuromotor effect of the aqueous and hexane extract of the fruits of Z. rhoifolium.Methods: As there were no preliminary reports of this study, the first observation was made through Irwin's test. The formalin and the rotarod test were performed to determine the analgesic and motor coordination effects, respectively. Results: All the evaluated treatments demonstrated to generate analgesia, anesthesia, passivity, reduction in the alarm reaction, and have antinociceptive activity in the formalin test; while only the high dose of the nonpolar extract generated a deficit in the motor performance of the rodents in the rotarod test. Conclusions: the antinociceptive effect of the aqueous and hexane extracts of this species' fruits was demonstrated. The hexane extract generated a neuromotor effect, which validates the ethnobotanical reports on Z. rhoifolium fruits.

Antecedentes: Colombia tiene una alta diversidad de plantas medicinales, incluyendo al Ta chuelo (Zanthoxylum rhoifolium), un árbol de la familia Rutaceae al que se le ha atribuido un potencial analgésico debido al uso por parte de las comunidades del Suroccidente Colombiano. Sin embargo, esta especie ha sido poco estudiada en Colombia, limitándose al aislamiento de compuestos con actividad antifúngica e insecticida, empleando las hojas, ramas y corteza de la planta en extractos acuosos y orgánicos; sin embargo, no se han realizado ensayos farmacológicos ni se han probado la actividad analgésica y neuromotora a partir de preparaciones con los frutos de esta planta. Objetivos: Evaluar el efecto analgésico y neuromotor del extracto acuoso y en hexano de los frutos de Z. rhoifolium. Métodos: Al no haber reportes preliminares de este estudio, se realizó la primera observación mediante el test de Irwin. Para determinar el efecto analgésico y neuromotor se realizó el test de formalina y el test de rotarod, respectivamente. Resultados: Todos los tratamientos evaluados demostraron generar analgesia, anestesia, pasividad, reducción en la reacción de alarma, tener actividad antinociceptiva en el test de formalina, mientras que solo la dosis alta del extracto apolar generó un déficit en el rendimiento motor de los roedores en el test de rotarod. Conclusiones: Se demostró el efecto antinociceptivo del extracto acuoso y en hexano de los frutos de esta especie y el efecto neuromotor generado por el extracto en hexano, validando los reportes etnobotánicos sobre los frutos de Z. rhoifolium.

Comparative evaluation of phasic and chemical antinociceptive action of a conventional and a novel anticonvulsants in experimental models of tail flick and formalin test

Background: Some antiepileptic drugs have been shown to be clinically efficacious in treatment of neuropathic pain and are being used by clinician.Methods: This study determined the analgesic effect of gabapentin (a conventional anticonvulsant) and levitiracetam (a novel anticonvulsant) in rats in different types of acute and chronic nociceptive test like tail flick and formalin test and compared its potency with a conventional non opioid analgesic diclofenac.Results: Per oral administration of gabapentin produced no any marked effect on early phase response of formalin test but significantly suppressed the late phase response while levitiracetam produced no any type of significant effect in both phases. In tail flick test gabapentin as well as levitiracetam produced no any significant analgesic effect while diclofenac produced significant reduction of pain in tail flick test as well as in both phases of formalin test.Conclusions: Thus, we have observed that gabapentin produced antinociception in chronic pain as second phase of formalin test reflects chronic inflammatory pain while levitiracetam did not produce any type of antinociceptive effect as it could not suppress the pain significantly in both tail flick and formalin test.

Antinociceptive local activity of 4-allyl-1-hydroxy-2-methoxybenzene (eugenol) by the formalin test: an anti-inflammatory effect

Eugenol has been employed for decades as a condiment, an antimycotic, an antibacterial, an antiviral, and an antioxidant, and it is one of the natural analgesics most frequently utilized for pain and inflammation. Our objective was to determine the analgesic/anti-inflammatory effect of eugenol compared with diclofenac, naproxen, and tramadol using the formalin test. The formalin method was used in 6- to 10-week-old Wistar rats (weighing 250 g each) divided into six groups: saline (0.9%); formalin (5%); diclofenac (250 µg/kg); naproxen (400 µg/kg); tramadol (500 µg/kg), and eugenol (1,400 µg/kg), in the intraplantar part of the hind-end trunk of the rats, with n = 5 per group. Eugenol diminished 44.4% of nociceptive behavior in phase 1 and 48% in phase 2 (p ≤0.05 vs formalin). Eugenol was shown to be 1.14 times more effective than diclofenac, but 1.62 and 1.75 times less effective than naproxen and tramadol, respectively, in phase 1 and 1.45 times less effective than diclofenac and naproxen and 1.66 less effective than tramadol in phase 2 (p ≤0.05). These data suggest that eugenol possesses moderate activity in the acute pain phase and greater activity in inflammatory-type pain, and both effects are comparable to those produced by diclofenac and are less than the effects produced by naproxen and tramadol in the formalin test

Preclinical screening of a novel compound, 2-chlorothiophene for analgesic activity in swiss albino mice

Background: Pain is often the first indication of disease or injury. Analgesics are the drugs used clinically for controlling pain. They relieve pain as a symptom, without affecting its cause. Currently available options are nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics for the management of pain. Long term use of existing analgesics causes significant disturbances in the body system. A search for new, safe and cost effective analgesic compound is in progress. Hence a study on 2-chlorothiophene, a novel compound has been carried out in different experimental animal models.Methods: The central analgesic activity of 2-chlorothiophene was evaluated by eddy’s hot plate method and compared to standard central analgesic, morphine. Both central and peripheral analgesic activities of 2-chlorothiophene were evaluated by formalin induced paw licking in mice and compared to a standard drug, aspirin.Results: There were 40mg/kg dose of 2-chlorothiophene has shown maximum Pain Inhibition Percentage (PIP) of 46.15% at 60 min compared to 128% by morphine in eddy’s hot plate method. Under Formalin test, 20mg/kg dose of 2-chlorothiophene has shown maximum PIP of 22.91% in early phase and 52.63% in late phase compared to 12.5% and 47.37% by aspirin. The results were statistically significant with p<0.05.Conclusions: 2-chlorothiophene found to have minimal central analgesic activity and significant peripheral analgesic activity as evident in eddy’s hot plate and formalin tests.

Anti-nociceptive effect of seed extract of Acacia tortilis in rodents

Background: Management of pain is a primary clinical concern for any pathology in medical field. Addiction liability of opioids and troublesome gastrointestinal side effects of NSAIDs leads to intensive research for compound with lesser side effects.The aim of the study to evaluate the anti-nociceptive activity of Acacia Tortilis Seed Extract (ATE) in experimental animals.Methods: First of all, animals were randomly allocated into four groups of six animals each. In acetic acid induced writhing test model, Group I (NC) served as vehicle control received saline/Tween 80 0.1%, 10ml/kg BW orally, group II (ATE-100) and III (ATE-200) received ATE in dose of 100 and 200mg/kg BW orally respectively and group IV received the standard drug diclofenac sodium in dose of 50 mg/kg BW orally. Group I to IV were same in rest of three experimental models. One additional group of standard drugs (group V) morphine sulfate in dose of 5 mg/kg BW subcutaneously (SC) was allocated for screening method hot plate and tail flick tests. In Formalin induced paw licking test, three additional groups (group V) morphine sulfate in dose of 5mg/kg BW SC, group VI- morphine+naloxone (5mg/kg SC +2mg/kg intra-peritoneally (IP) and group VII - ATE+ naloxone (200mg/kg BW orally +2mg/kg BW IP) were also made.Results: The ATE when administered orally in dose of 100 and 200mg/ kg body weight (BW), produced significant analgesic activity (P <0.01) in acetic acid induced writhing syndrome and late phase of formalin test. In the hot plate test in mice and tail flick test in rats, ATE in same doses also showed significant analgesic activity (P <0.05) which is almost equally efficacious to standard drug diclofenac sodium (50mg/kg BW orally) but far less efficacious than morphine sulfate (5mg/kg BW subcutaneous).ATE (200mg/Kg BW orally) activity did not blocked by naloxone (2mg/kg intra-peritoneal).Conclusions: ATE possesss significant anti-nociceptive activity as evidenced in all the animal models of nociception. It might exert its effect through the peripheral mechanism of analgesic action possibly by interference in biosynthesis, release and/or action of prostaglandins and leukotrienes.

Antinociceptive local effect of the combination of dexketoprofen trometamol and chlorhexidine gluconate in a formalin test: an additive effect

ABSTRACT A drug delivery system (DDS) with analgesic and antibacterial properties would be desirable for the local control of post-operatory pain and the prevention for surgical site infection (SSI). The objective of the present study was to evaluate the antinociceptive effect of the combination between dexketoprofen trometamol (DXT) and chlorhexidine gluconate (CHX) in the formalin pain model. Different doses of CHX were combined with DXT and were locally administered in rats paw simultaneously with 5% formalin dilution. Flinches were documented and the antinociceptive effect was calculated. The area under the curve of each experimental group were calculated and the % of antinociception were compared. The groups of CHX and DXT showed similar antinociceptive effect. The combination groups (DXT-CHX) showed higher antinociceptive effect that the one obtained with individual molecules. Besides the confirmation of DXT local antinociceptive properties, CHX also showed a positive effect; and an additive effect when combined with DXT

Peripheral Leptin Signaling Mediates Formalin-Induced Nociception / 神经科学通报·英文版

Accumulating evidence suggests that obesity is associated with chronic pain. However, whether obesity is associated with acute inflammatory pain is unknown. Using a well-established obese mouse model induced by a high-fat diet, we found that: (1) the acute thermal pain sensory threshold did not change in obese mice; (2) the model obese mice had fewer nociceptive responses in formalin-induced inflammatory pain tests; restoring the obese mice to a chow diet for three weeks partly recovered their pain sensation; (3) leptin injection induced significant phosphorylation of STAT3 in control mice but not in obese mice, indicating the dysmodulation of topical leptin-leptin receptor signaling in these mice; and (4) leptin-leptin receptor signaling-deficient mice (ob/ob and db/db) or leptin-leptin receptor pathway blockade with a leptin receptor antagonist and the JAK2 inhibitor AG 490 in wild-type mice reduced their nociceptive responses in formalin tests. These results indicate that leptin plays a role in nociception induced by acute inflammation and that interference in the leptin-leptin receptor pathway could be a peripheral target against acute inflammatory pain.

Antinociceptive effect of intrathecal sec-O-glucosylhamaudol on the formalin-induced pain in rats

BACKGROUND: The root of Peucedanum japonicum Thunb., a perennial herb found in Japan, the Philippines, China, and Korea, is used as an analgesic. In a previous study, sec-O-glucosylhamaudol (SOG) showed an analgesic effect. This study was performed to examine the antinociceptive effect of intrathecal SOG in the formalin test. METHODS: Male Sprague-Dawley rats were implanted with an intrathecal catheter. Rats were randomly treated with a vehicle and SOG (10 µg, 30 µg, 60 µg, and 100 µg) before formalin injection. Five percent formalin was injected into the hind-paw, and a biphasic reaction followed, consisting of flinching and licking behaviors (phase 1, 0–10 min; phase 2, 10–60 min). Naloxone was injected 10 min before administration of SOG 100 µg to evaluate the involvement of SOG with an opioid receptor. Dose-responsiveness and ED50 values were calculated. RESULTS: Intrathecal SOG showed a significant reduction of the flinching responses at both phases in a dose-dependent manner. Significant effects were showed from the dose of 30 µg and maximum effects were achieved at a dose of 100 µg in both phases. The ED50 value (95% confidence intervals) of intrathecal SOG was 30.3 (25.8–35.5) µg during phase 1, and 48.0 (41.4–55.7) during phase 2. The antinociceptive effects of SOG (100 µg) were significantly reverted at both phases of the formalin test by naloxone. CONCLUSIONS: These results demonstrate that intrathecal SOG has a very strong antinociceptive effect in the formalin test and it seems the effect is related to an opioid receptor.

Spared nerve injury model to study orofacial pain.

Background & objectives: There are many difficulties in generating and testing orofacial pain in animal models. Thus, only a few and limited models that mimic the human condition are available. The aim of the present research was to develop a new model of trigeminal pain by using a spared nerve injury (SNI) surgical approach in the rat face (SNI-face). Methods: Under anaesthesia, a small incision was made in the infraorbital region of adult male Wistar rats. Three of the main infraorbital nerve branches were tightly ligated and a 2 mm segment distal to the ligation was resected. Control rats were sham-operated by exposing the nerves. Chemical hyperalgesia was evaluated 15 days after the surgery by analyzing the time spent in face grooming activity and the number of head withdrawals in response to the orofacial formalin test. Results: SNI-face rats presented a significant increase of the formalin-induced pain-related behaviours evaluated both in the acute and tonic phases (expected biphasic pattern), in comparison to sham controls. Interpretation & conclusions: The SNI-face model in the rat appears to be a valid approach to evaluate experimental trigeminal pain. Ongoing studies will test the usefulness of this model to evaluate therapeutic strategies for the treatment of orofacial pain.

Analgesic and anti-inflammatory activities of hydro-alcoholic extract of Lavandula officinalis in mice: possible involvement of the cyclooxygenase type 1 and 2 enzymes

Abstract Lavandula officinalis Chaix, Lamiaceae, extracts can inhibit inflammation and also pain induced by formalin in mice. This study evaluated the effects of L. officinalis hydro-alcoholic extract on pain induced by formalin and also cyclooxygenase (COX) type 1 and 2 activity in mice. To evaluate probable analgesic and anti-inflammatory effects of the extract, flowers were prepared by maceration and extraction in alcohol and their analgesic effects were studied in male mice, using formalin and hot plate tests. The effect of intraperitoneal hydro-alcoholic extracts of L. officinalis (100, 200, 250, 300, 400 and 800 mg/kg), subcutaneous morphine (10 mg/kg), dexamethasone (10 mg/kg; i.p.) and indomethacin (10 mg/kg; i.p.) on formalin induced pain were studied. Our results indicated that administration of the extract (100, 200, 250, 300, 400 and 800 mg/kg; i.p.) has inhibitory effects on inflammation induced by formalin injection into the animals hind paw. Moreover, this inhibitory effect was equal to the effects of morphine, dexamethasone and indomethacin. The extract in100, 200 and 300 mg/kg; significantly reduced heat-induced pain. The extract also reduced COX activity in dose dependent manner, where the inhibitory effect on COX1 activity was 33% and on COX2 activity was 45%. Here for the first time we show that L. officinialis extract can modulate pain and inflammation induced by formalin by inhibition of COX enzymes.

Antinociceptive and Anti-inflammatory Effects of Combined Administration of a-tocopherol and Diclofenac.

Background: Nonsteroidal anti-inflammatory drugs such as diclofenac are used for relief of pain and inflammation, but frequently cause gastrointestinal complications. This study aimed to explore that combination of diclofenac and α-tocopherol (αT) are better analgesic as well as anti-inflammatory agent than that of diclofenac alone. Objective: To assess the effects of combination of diclofenac with α-tocopherol on pain and inflammation. Methods: This prospective experimental study was conducted in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka between January to December 2013. For this purpose, 15 male Long Evans rats were studied. On the basis of vitamin and drug administrations, the rats were divided into three (3) groups (5 rats in each). Control group received normal saline, one experimental group received diclofenac sodium (DS) at a dose of 10 mg/kg/body weight, and another experimental group received combination of DS with αT at a dose of 10 mg/kg/body weight and 500mg/kg/body weight, respectively. All the groups received single dose and equal volume (1 ml) through intraperitoneal route 1 hour before the test. Just one hour after administrations, they were subjected to formalin test followed by formalin induced paw edema test. The data were statistically analyzed by ANOVA followed by Bonferroni Post Hoc test. Results: Combined administration of DS and αT significantly (p<0.001) lowered the variables for nociceptive pain, central analgesic activity, inflammatory pain and inflammation than individual intervention of DS. Conclusion: From this study it may be concluded that, combined administration of diclofenac sodium and ±-tocopherol were more effective in lowering pain and inflammation than individual administration of diclofenac.

Hyperalgesic effect of subarachnoid administration of phentolamine in mice / Hyperalgesic effect of subarachnoid administration of phentolamine in mice / Efecto hiperalgésico de la fentolamina por vía subaracnoidea en ratones

BACKGROUND AND OBJECTIVES: Painful phenomenon is one of the most important and complex experiences. Phentolamine is a non-selective alpha-adrenergic antagonist. The objective of this study was to compare the effect of increasing doses of phentolamine into subarachnoid space in rats in the modulation of painful phenomenon. METHODS: 84 male Wistar rats were divided into formalin and plantar incision groups, subdivided into six subgroups (n = 7). Control group received only saline (10 µL); active subgroups received phentolamine 10 µmg (GF10), 20 mg (GF20), 30 mg (GF30), 40 mg (GF40), and 50 g (GF50). In formalin group, pain was induced by injection of 50 µL of 2% formalin in dorsal region of right posterior paw. In plantar incision group, pain was induced by plantar incision and evaluated using von Frey filaments. Induction and maintenance of anesthesia were performed with 3% halothane for catheter placement into subarachnoid space and plantar incision. Statistical analysis was performed using the JMP program from SAS with 5% significance level. RESULTS: Phentolamine at doses of 20 and 30 g increased the algesic response in the intermediate phase of the formalin test. In plantar incision test, it had hyperalgic effect on first, third, fifth, and seventh days at a dose of 10 g and on first, third, and fifth days at a dose of 20 g and on fifth day at a dose of 30 g. CONCLUSION: Subarachnoid administration of phentolamine showed hyperalgesic effect, possibly due to the involvement of different subclasses of alpha-adrenergic receptors in modulating pain pathways. .

JUSTIFICATIVA E OBJETIVOS: O fenômeno doloroso é uma das mais importantes e complexas experiências. A fentolamina é antagonista alfa-adrenérgico não seletivo. O objetivo foi comparar os efeitos de doses crescentes da fentolamina, por via subaracnóidea, em ratos na modulação do fenômeno doloroso. MÉTODO: Foram usados 84 ratos Wistar machos, divididos nos grupos formalina e incisão plantar, subdivididos em seis subgrupos (n = 7). No subgrupo controle (GC) apenas salina (10 µL), nos subgrupos ativos, 10 µg de fentolamina (GF10), 20 µg (GF20), 30 µg (GF30), 40 µg (GF40) e 50 µg (GF50). No grupo formalina, a dor foi induzida com injeção de 50 µL de formalina a 2%, na região dorsal da pata posterior direita. No grupo incisão plantar, a dor foi induzida por incisão plantar e avaliação pelos filamentos de Von Frey. Indução e manutenção anestésica com halotano a 3% para introdução de cateter no espaço subaracnóideo e feitura da incisão plantar. Análise estatística dos resultados pelo programa JMP do SAS com nível de significância 5%. RESULTADOS: A fentolamina nas doses de 20 e 30 µg produziu aumento da resposta álgica na fase intermediária do teste da formalina. No teste da incisão plantar, promoveu efeito hiperálgico no primeiro, terceiro, quinto e sétimo dias na dose de 10 µg, no primeiro, terceiro e quinto dias na dose de 20 µg e no quinto dia na dose de 30 µg. CONCLUSÃO: A fentolamina por via subaracnóidea promoveu efeito hiperálgico, possivelmente pela participação de diferentes subclasses de receptores alfa-adrenérgicos nas vias modulatórias da dor. .

JUSTIFICACIÓN Y OBJETIVOS: El fenómeno doloroso es una de las más importantes y complejas experiencias. La fentolamina es un antagonista alfaadrenérgico no selectivo. El objetivo fue comparar los efectos de dosis crecientes de fentolamina por vía subaracnoidea en la modulación del fenómeno doloroso en ratones. MÉTODO: Fueron usados 84 ratones Wistar machos, divididos en los grupos formalina e incisión plantar, subdivididos en 6 subgrupos (n = 7). En el subgrupo control (GC) solamente se administró solución salina (10 µL); en los subgrupos activos, 10 µg de fentolamina (GF10), 20 µg (GF20), 30 µg (GF30), 40 µg (GF40) y 50 µg (GF50). En el grupo formalina, el dolor fue inducido con una inyección de 50 µL de formalina al 2% en la región dorsal de la pata posterior derecha. En el grupo incisión plantar, el dolor se indujo por incisión plantar y evaluación por los filamentos de Von Frey. La inducción y el mantenimiento anestésico se llevó a cabo con halotano al 3% para la introducción de catéter en el espacio subaracnoideo y la realización de la incisión plantar. El análisis estadístico de los resultados se hizo mediante el programa JMP(r) del SAS con un nivel de significación del 5%. RESULTADOS: La fentolamina en las dosis de 20 y 30 µg produjo un aumento de la respuesta de dolor en la fase intermedia del test de la formalina. En el test de la incisión plantar, generó un efecto hiperalgésico en el primero, tercero, quinto y séptimo días con dosis de 10 µg; en el primero, tercero y quinto días con dosis de 20 µg; y en el quinto día con dosis de 30 µg. CONCLUSIÓN: La fentolamina por vía subaracnoidea generó un efecto hiperalgésico posiblemente por la participación de diferentes subclases de receptores alfaadrenérgicos en las vías moduladoras del dolor. .

One-time Exposure to General Anesthetics Alters Nociceptive Response and Nucleotide Hydrolysis in Infant Rats.

Aims: The objective was to evaluate the single exposure of general anesthetics with or without a surgical procedure at postnatal day 14 (P14) on nociceptive behavioral responses. Furthermore, we evaluated ectonucleotidase activities at P14 and P30. Place of Study: All experiments were performed at the Animal Experimentation Unit of Hospital de Clínicas de Porto Alegre. The Institutional Committee approved the experimental protocol f (GPPG-HCPA protocol No: 08149). Methodology: Fourteen-day-old male Wistar rats were divided into two experimental designs (ED): the 1st ED – control (C), isoflurane (ISO), isoflurane/surgery (ISO-SUR) and the 2nd ED – control (C), fentanyl/S(+)-ketamine (FK) and fentanyl/S(+)- ketamine/surgery (FK-SUR). Nociceptive responses were evaluated using the formalin and tail-flick tests, and the ectonucleotidase activities were evaluated by spinal cord synaptosome. All assessments were performed at P14 and P30. Results: The FK and FK-SUR groups displayed an increased latency at P30. For the ectonucleotidase activity analysis, the following results were observed: (a) in the 1st ED, the ISO group displayed a reduction in ATPase and ADPase, and both ISO and ISOSUR displayed a reduction in AMPase activity at P14; (b) in the 2nd ED, the FK group displayed an increase in AMPase activity at P14 and increased ATPase activity at P30, and both FK and FK-SUR exhibited an increase in AMPase activity at P30. Conclusion: Our results indicate that single administration of general anesthetics at P14 is able to promote changes in the nociceptive response in the intermediate-term, and in the ectonucleotidase activities in the short- and medium-terms.

Antinociceptive evaluation of anticonvulsant gabapentin with a conventional nonopioid analgesic in phasic and tonic animal model of acute and chronic pain.

Background: Some antiepileptic drugs have been shown to be clinically efficacious in treatment of neuropathic pain and are being used by clinician. Methods: This study determined the analgesic effect of gabapentin in rats in biphasic animal pain model of acute and chronic inflammatory pain and compared its potency with a conventional nonopioid analgesic diclofenac. Results: Per oral administration of gabapentin produced no any marked effect on early phase response of formalin test, but significantly suppressed the late phase response, while diclofenac produced significant anti-nociceptive effect in both phases of formalin test. Conclusion: Thus, we have observed that gabapentin produced antinociception in second phase of formalin test, which reflects chronic inflammatory pain.

Evaluation of antinociceptive and anti-inflammatory activities of the topical preparation of Cipura paludosa (Iridaceae) / Avaliação das atividades antinociceptiva e anti-inflamatória de preparação tópica de Cipura paludosa (Iridaceae)

Alho do mato (Cipura paludosa, Iridaceae) is a medicinal plant found in the Amazon rain forest, North of Brazil. It has been used to treat algic, inflammatory and infectious processes. The aim of this study was to evaluate the anti-inflammatory and antinociceptive action of the crude Cipura paludosa ethanolic extract at concentrations ranging between 2.0 and 4.0% in Oil and Water cream formulations for topical use. The physical-chemical stability of the formulations was monitored over a six-month period with the use of accelerated stability tests. In order to evaluate the anti-inflammatory and antinociceptive activities, we used a paw edema test induced by carrageenan and a formalin test, respectively. The paw edema test showed that there was a statistical difference in the control group in relation to the treatments. The formalin test did not confirm antinociceptive action of the treatments with the extract in the early phase of the test. However, statistical difference was confirmed for the treatments in relation to the control in the late phase. The antinociceptive and anti-inflammatory activities of Cipura paludosa preparations, as demonstrated in the results, at least partially support the ethno-medical uses of this plant.

Allho do mato (Cipura paludosa, Iridaceae) é uma planta medicinal encontrada na floresta Amazônica, norte do Brasil. Essa planta tem sido usada para tratar dores, processos inflamatórios e infecciosos. O objetivo do estudo foi avaliar a ação anti-inflamatória e antinociceptiva do extrato bruto etanólico de Cipura paludosa, nas concentrações que variaram entre 2,0 e 4,0%, em formulações de cremes óleo e água de uso tópico. A estabilidade físico-química das formulações foi monitorada ao longo de um período de seis meses, com a aplicação de ensaios de estabilidade acelerada. A fim de avaliar as atividades anti-inflamatória e antinociceptiva, utilizou-se um teste de edema de pata induzido por carragenina e um teste de formalina, respectivamente. O teste de edema de pata mostrou que houve uma diferença significativa no grupo controle em relação aos tratamentos. O teste da formalina não confirmou efeito antinociceptivo dos tratamentos com o extrato, na primeira fase do ensaio. No entanto, a diferença estatística foi confirmada para os tratamentos em relação ao controle na segunda fase. As atividades antinociceptiva e anti-inflamatória das preparações com Cipura paludosa confirmam de forma parcial o uso etno-médico desta planta.

Antinociceptive Effect of Ethanolic Extract of Hybanthus enneaspermus Leaf in Rats.

Aims: To test the hypothesis that Hybanthus enneaspermus leaf has an antinociceptive effect. Methodology: Seventy-two male rats were randomly divided in a blinded fashion into 4 groups each for the tail immersion test (n=12 per group) and formalin test (n=6 per group). Group 1 (control) received 0.6 ml of distilled water. Group 2 received 100 mg/kg of acetaminophen (paracetamol). Group 3 and 4 received 500 mg/kg and 1000 mg/kg of ethanolic extract of Hybanthus enneaspermus leaf (EEHE) respectively. Results: In the formalin test, oral administration of 500 mg/kg and 1000 mg/kg EEHE caused inhibitions of 62.48% and 72% in the early phase and 70.54% and 78.63% in the late phase respectively. The 1000 mg/kg dose significantly reduced the paw licking time when compared to the standard drug (acetaminophen) in the formalin test. The 500 mg/kg and 1000 mg/kg doses significantly increased the tail flick latency in a manner comparable to acetaminophen. Conclusion: This study showed that the leaf has an anti-nociceptive effect.

Epidural Dexamethasone Decreased Inflammatory Hyperalgesia and Spinal cPLA2 Expression in a Rat Formalin Test

PURPOSE: The aim of this study was to investigate the effect of epidural dexamethasone on analgesia and cytosolic phospholipase A2 (cPLA2) expression in the spinal cord in a rat formalin test. MATERIALS AND METHODS: Epidural dexamethasone injection was performed to Sprague-Dawley rats with a 25 gauge needle under fluoroscopy. Following the epidural injection, a formalin induced pain behavior test was performed. Next, the spinal cords corresponding to L4 dorsal root ganglion was extracted to observe the cPLA2 expression. RESULTS: There were no differences in pain response during phase I among the groups. The phase II pain response in 300 microg of epidural dexamethasone group decreased as compared to control, 30 microg of epidural dexamethasone, 100 microg of epidural dexamethasone, and 300 microg of systemic dexamethasone groups. The expression of cPLA2 decreased in Rexed laminae I-II in 300 microg of the epidural dexamethasone group compared with the ones in the control group. CONCLUSION: Taken together, these results suggest that 300 microg of epidural dexamethasone has an attenuating effect on the peripheral inflammatory tissue injury induced hyperalgesia and this effect is mediated through the inhibition of intraspinal cPLA2 expression and the primary site of action is the laminae I-II of the spinal cord.

Acute Systemic Infusion of Bupropion Decrease Formalin Induced Pain Behavior in Rat

BACKGROUND: The chronic pain can disturb physical, psychological, and social performances. Analgesic agents are widely used but some antidepressants (ADs) showed analgesia also. Bupropion is using for smoke cessation but it can change morphine withdrawal signs such as pain. This study tested the acute systemic effect of bupropion on formalin induced pain behavior in rats. METHODS: Wistar male healthy rats were divided into 7 groups (control, sham, and 5 treated groups with 10, 30, 90, 120, and 200 mg/kg of bupropion, i.p.). The bupropion injected 3 hours prior to formalin induced pain behavior. Formalin (50 microl, 2.5%) was injected subcutaneously in dorsal region of right hindpaw in all animals. Nociceptive signs were observed continuously on-line and off-line each minute. Common pain scoring was used for pain assessment. RESULTS: The analysis of data by one-way ANOVA showed that bupropion can reduce pain scores in the second phase but not in first phase. Bupropion decreased the licking/biting duration significantly in first and second phase of formalin test. CONCLUSIONS: The results showed that bupropion has analgesic effects at systemic application. The change of second phase of the pain behavior was significant and it revealed that central mechanisms involve in bupropion analgesia.

Effects of Co-Administration of Intrathecal Nociceptin/Orphanin FQ and Opioid Antagonists on Formalin-Induced Pain in Rats

PURPOSE: Nociceptin/orphanin FQ (N/OFQ) as an endogeneous hexadecapeptide is known to exert antinociceptive effects spinally. The aims of this study were to demonstrate the antinociceptive effects of i.t. N/OFQ and to investigate the possible interaction between N/OFQ and endogenous opioid systems using selective opioid receptor antagonists in rat formalin tests. MATERIALS AND METHODS: I.t. N/OFQ was injected in different doses (1-10 nmol) via a lumbar catheter prior to a 50 microL injection of 5% formalin into the right hindpaw of rats. Flinching responses were measured from 0-10 min (phase I, an initial acute state) and 11-60 min (phase II, a prolonged tonic state). To observe which opioid receptors are involved in the anti-nociceptive effect of i.t. N/OFQ in the rat-formalin tests, naltrindole (5-20 nmol), beta-funaltrexamine (1-10 nmol), and norbinaltorphimine (10 nmol), selective delta-, micro- and kappa-opioid receptor antagonists, respectively, were administered intrathecally 5 min after i.t. N/OFQ. RESULTS: I.t. N/OFQ attenuated the formalin-induced flinching responses in a dose-dependent manner in both phases I and II. I.t. administration of naltrindole and beta-funaltrexamine dose-dependently reversed the N/OFQ-induced attenuation of flinching responses in both phases; however, norbinaltorphimine did not. CONCLUSION: I.t. N/OFQ exerted an antinociceptive effect in both phases of the rat-formalin test through the nociceptin opioid peptide receptor. In addition, the results suggested that delta- and micro-opioid receptors, but not kappa-opioid receptors, are involved in the antinociceptive effects of N/OFQ in the spinal cord of rats.

The Effects of Pre-emptive Administration of Ketamine and norBNI on Pain Behavior, c-Fos, and Prodynorphin Protein Expression in the Rat Spinal Cord after Formalin-induced Pain Is Modulated by the DREAM Protein

BACKGROUND: We investigated the effects of pre-emptive administration of ketamine and norBNI on pain behavior and the expression of DREAM, c-Fos, and prodynorphin proteins on the ipsilateral side of the rat spinal cord at 2 and 4 hours after formalin injection. METHODS: Eighty-four male Sprague Dawley rats were divided into 4 major groups consisting of control rats (C) (n = 12), rats given only formalin injections (F) (n = 24), and rats treated with pre-emptive administration of either ketamine (K+F) (n = 24) or norBNI (N+F) (n = 24). The non-control groups were further divided into subgroups consisting of rats that were sacrificed at 2 and 4 hours (n = 12 for each group) after formalin injection. Pain behavior was recorded for 1 hour. After 2 and 4 hours, the rats were sacrificed and the spinal cords (L4-L5 sections) were removed for immunohistochemistry and Western blot analysis. RESULTS: The pain behavior response was reduced in the K+F group compared to the other groups during the second phase of the formalin pain response. We detected an increase in the nuclear DREAM protein level in the K+F group at 2 and 4 hours and a transient decrease in the N+F group at 2 hours; however, it increased at 4 hours after injection. Fos-like immunoreactivity (FLI) and Prodynorphin-like immunoreactivity (PLI) neurons decreased in the K+F group but increased in the N+F group at 2 hours after injection. While FLI decreased, PLI increased in all groups at 4 hours after injection. CONCLUSIONS: We suggest that NMDA and kappa opioid receptors can modulate DREAM protein expression, which can affect pain behavior and protein transcriptional processes at 2 hours and bring about either harmful or protective effects at 4 hours after formalin injection.