Antinociceptive Activity of Methanol Extract of Tabebuia hypoleuca (C. Wright ex Sauvalle) Urb. Stems.

OBJECTIVE: The aim of this study was to evaluate the antinociceptive activity of the methanol extract of Tabebuia hypoleuca stems (THME). MATERIALS AND METHODS: The animals were divided into 5 groups of 8 mice for each test (negative controls, positive controls, and 3 groups treated with THME at doses of 150, 300, and 500 mg/kg, p.o.). The antinociceptive effect of THME was evaluated using the writhing, formalin, tail flick, and hot plate models in mice. RESULTS: In the writhing test, THME (150, 300, and 500 mg/kg) produced significantly (p < 0.001) fewer writhes induced by acetic acid than in the control group. In the formalin test, the licking time for THME at doses of 300 and 500 mg/kg was significantly shorter (p < 0.001) compared to the control group in the first phase of the formalin test, whereas in the second phase only the dose of 500 mg/kg showed an antinociceptive effect. In addition, THME at doses of 300 and 500 mg/kg significantly increased the latency time in the tail flick test (p < 0.05 and p < 0.001, respectively) and in the hot plate test (p < 0.01 and p < 0.001, respectively) compared to the control group. CONCLUSIONS: These results show that THME had antinociceptive activity using several models of nociception, and they suggest that the effect is mediated by the participation of both peripheral and central antinociceptive mechanisms.

Antinociceptive and anti-inflammatory effects of Lantana camara L. extract in mice / Efeitos antinociceptivos do extrato de Lantana camara L. em camundongos

ABSTRACT: he Lantana camara L. belongs to the family Verbenaceae, which contains several active compounds in leaves and roots and which are reported to have medicinal and insecticidal properties. Studies of plants within the same family show the existence of anti-inflammatory activity in paw edema induced by carrageenan, serotonin and histamine and analgesic activity in the acetic acid writhing and tail-flick tests. The present study investigated whether the L. camara extract (ACE) also exerts these effects. The ACE toxicity was studied in male mice, and the percentage of mortality recorded 7 days after treatment was assessed. The ACE was evaluated as an antinociceptive agent in the hot plate, tail-flick and acetic acid writhing tests at a nontoxic dose of 1.0 g/Kg. The results showed that 1.5 g/Kg of ACE was not able to cause death, and doses of 3.0 and 4.0 g/Kg caused 50% and 60% death, respectively, in male mice. In all of the antinociceptive tests, 1 g/Kg of ACE markedly reduced responses to pain. Our findings suggest that ACE may have active anti-inflammatory and antinociceptive properties in much smaller doses than toxic.

RESUMO: Lantana camara L. pertence à família Verbenaceae, a qual contem muitos princípios ativos em suas folhas e raízes com propriedade medicinais e inseticidas. Estudos com plantas da mesma família mostram a existência de propriedades antinflamatórias no modelo de edema de pata induzido pela carragenina, serotonina e histamina, além da atividade analgésica nos testes de contorção induzida pelo ácido acético e da retirada da cauda por estímulo térmico. O presente trabalho investigou os efeitos tóxicos e antinociceptivos do extrato de L. camara (ACE) em camundongos. Para tanto, investigou-se a porcentagem de mortes em 7 dias após a administração de diferentes doses do extrato. Avaliou-se também os efeitos antinociceptivos do ACE pelos testes da placa quente, estimulação térmica da cauda e contorções abdominais induzidas pelo ácido acético com a dose não-tóxica [1,0 g/Kg]. Os resultados mostraram que 1,5 g/Kg do ACE não causou mortalidade, enquanto que 3,0 e 4,0 g/Kg promoveram 50 e 60% de mortalidade, respectivamente. Em todos os testes antinociceptivos, a dose de 1,0 g/Kg do ACE reduziu a resposta à dor. Os presentes resultados indicam que o ACE apresenta propriedades antinflamatórias e analgésicas em doses muito menores que a tóxica.

Tiopental altera a resposta nociceptiva de ratos jovens em longo prazo / Thiopental alters long term nociceptive response of young rats

The objective of this study was to evaluate the long term nociceptive response determined by use of two general anesthetics, one intravenous and the other inhalatory, in young animals. In the first experiment, the animals of 21 days of age were divided into control (saline) and thiopental (35 mg/kg, i.p.) groups. In the second experiment, rats of the same age were divided in two groups ­ halothane (2%) and control. In experiment 1, there was difference between groups ­ reduction of tail-flick latency in the group thiopental (P< 0.05). In experiment 2, there were no differences between groups or interaction between time versus group (F(1,19)=0.11 for groups, P>0.05; F(1,19)=0.032 for the interaction, P>0.05). The results obtained in this study showed that halothane did not alter the nociceptive response in young animals. However, the thiopental induced hyperalgesic response in rats. (AU)

O objetivo desse estudo foi avaliar a resposta nociceptiva a longo prazo relacionada ao uso de dois anestésicos gerais ­ um intravenoso e outro inalatório, em animais jovens. No primeiro experimento, os animais de 21 dias de idade foram divididos nos grupos controle (solução salina) e tiopental sódico (35 mg/kg, i.p.). No segundo experimento, animais de mesma idade foram divididos em dois grupos ­ halotano (2%) e controle. No Experimento 1, houve redução da latência de retirada da cauda no grupo tiopental (P<0,05). No Experimento 2, não houve diferença entre os grupos ou interação entre grupo x tempo (F(1,19)=0,11 para grupos, P>0,05; F(1,19)=0,032 para a interação, P>0,05). Os resultados obtidos nesse estudo demonstraram que o halotano não altera a resposta nociceptiva em animais jovens. Entretanto, o tiopental induziu resposta hiperalgésica nestes ratos.(AU)

The antinociceptive effect of stimulating the retrosplenial cortex in the rat tail-flick test but not in the formalin test involves the rostral anterior cingulate cortex.

The stimulation of the retrosplenial cortex (RSC) is antinociceptive in the rat tail-flick and formalin tests. The rat RSC is caudal to and send projections to the ipsilateral anterior cingulate cortex (ACC), which is also involved in pain processing. This study demonstrated that pre-treating the rostral (rACC), but not the caudal ACC with CoCl2 (1mM), or the rACC ablation increased the duration of the antinociceptive effect evoked by a 15-s period of electrical stimulation (AC, 60Hz, 20µA) of the RSC in the rat tail-flick. Injecting the GABA-A antagonist bicuculline (50ng/0.25µL), but not the GABA-B antagonist phaclofen (300ng/0.25µL) into the rACC also increased the duration of the stimulation-induced antinociception from the RSC. In contrast, the effects of rACC stimulation persisted after the injection of CoCl2 (1mM) into the RSC. The injection of CoCl2 into the rACC did not change the nociceptive behavior of rats during phase 1 of the formalin response but reduced licking response duration during phase 2. This effect was similar in sham or stimulated animals at the RSC. We conclude that the antinociceptive effect of stimulating the RSC in the rat tail-flick test is modulated by the rACC involving GABA-A receptors in this cortex. In contrast, the antinociceptive effect of stimulating the RSC in the formalin test does not involve the rACC.

Evaluación de la actividad analgésica central de las hojas de Maytenus macrocarpa (Ruiz & Pav.) Briq. (chuchuhuasi) / Evaluation of the central analgesic activity of the leaves of Maytenus macrocarpa (Ruiz & Pav.) Briq. (chuchuhuasi)

Introducción: Maytenus macrocarpa Ruiz & Pav.) Briq (chuchuhuasi), es una planta medicinal peruana, a la cual se le atribuyen efectos: antidisentérico, antidiarreico, analgésico, antiinflamatorio, entre otros. Objetivo: explorar la actividad analgésica central de las hojas de M. macrocarpa, en ratones, mediante el modelo de retirada de la cola. Métodos: a 50 ratones albinos (25 g promedio), divididos en 5 grupos, se les administró por la vía oral lo siguiente: M. macrocarpa 1000 y 1500 mg/kg, Tramadol 10 mg/kg, agua destilada (placebo) 0,1ml /10 g, y un grupo control. Se evalúo el dolor en el roedor, midiendo el promedio del período de latencia, después de 6 mediciones de intervalos de 30 minutos. Asimismo, se determinó el porcentaje del efecto máximo posible (% MPE, por sus siglas en inglés). Resultados: chuchuhuasi 1000 mg/kg, presentó un basal de 2,781 segundos, frente a 4,135 segundos a los 120 minutos. Chuchuhuasi 1500 mg/kg, presentó un basal de 2,467 segundos, frente a 4,385 segundos a los 180 minutos; frente al control presentaron un valor p>0,05. Tramadol tuvo un basal de 2,030 segundos, frente a 5,173 segundos, a los 30 minutos; frente al control presento un valor p<0,05. El grupo placebo fue no significativo. El % MPE fue de 19 % para chuchuhuasi 1000 mg/kg, 14 % para chuchuhuasi 1500 mg/kg, y 37 % para Tramadol. Conclusión: el efecto analgésico central de las hojas de M. macrocarpa en el modelo de retirada de la cola fue no significativo, el máximo % MPE fue de 19 %, con chuchuhuasi a 1000 mg/kg.

Introduction: Maytenus macrocarpa (Ruiz & Pav.) Briq (chuchuhuasi) is a Peruvian medicinal plant which has been attributed antidysenteric, antidiarrheal, analgesic and anti-inflammatory effects, among others. Objective: explore the central analgesic activity of M. macrocarpa leaves in mice using the tail-flick model. Methods: fifty albino mice (25 g average weight) were divided into 5 groups and administered the following substances by oral route: M. macrocarpa 1 000 and 1 500 mg/kg, Tramadol 10 mg/kg, distilled water (placebo) 0.1 ml/10 g, and a control group. Pain was evaluated by estimating the average latency period after taking 6 measurements at 30 minute intervals. Percent maximum possible effect (% MPE) was also determined. Results: baseline time for chuchuhuasi 1 000 mg/kg was 2.781 seconds vs. 4.135 seconds at 120 minutes. Baseline time for chuchuhuasi 1 500 mg/kg was 2.467 seconds vs. 4.385 seconds at 180 minutes; p value vs. control was p>0.05. Baseline time for Tramadol was 2.030 seconds vs. 5.173 seconds at 30 minutes; p value vs. control was p>0.05. The placebo group was not significant. % MPE was 19 % for chuchuhuasi 1 000 mg/kg, 14 % for chuchuhuasi 1 500 mg/kg and 37 % for Tramadol. Conclusion: the central analgesic effect of M. macrocarpa leaves on the tail-flick model was not significant. Percent maximum possible effect was 19 % with chuchuhuasi 1 000 mg/kg.

Ethyl-p-methoxycinnamate isolated from kaempferia galanga inhibits inflammation by suppressing interleukin-1, tumor necrosis factor-α, and angiogenesis by blocking endothelial functions

OBJECTIVE: The present study aimed to investigate the mechanisms underlying the anti-inflammatory and anti-angiogenic effects of ethyl-p-methoxycinnamate isolated from Kaempferia galanga. METHODS: The anti-inflammatory effects of ethyl-p-methoxycinnamate were assessed using the cotton pellet granuloma assay in rats, whereby the levels of interleukin-1 and tumor necrosis factor-α were measured in the animals' blood. In addition, the levels of interleukin, tumor necrosis factor, and nitric oxide were measured in vitro using the human macrophage cell line (U937). The analgesic effects of ethyl-p-methoxycinnamate were assessed by the tail flick assay in rats. The anti-angiogenic effects were evaluated first by the rat aortic ring assay and, subsequently, by assessing the inhibitory effects of ethyl-p-methoxycinnamate on vascular endothelial growth factor, proliferation, migration, and tube formation in human umbilical vein endothelial cells. RESULTS: Ethyl-p-methoxycinnamate strongly inhibited granuloma tissue formation in rats. It prolonged the tail flick time in rats by more than two-fold compared with the control animals. The inhibition of interleukin and tumor necrosis factor by ethyl-p-methoxycinnamate was significant in both in vivo and in vitro models; however, only a moderate inhibition of nitric oxide was observed in macrophages. Furthermore, ethyl-p-methoxycinnamate considerably inhibited microvessel sprouting from the rat aorta. These mechanistic studies showed that ethyl-p-methoxycinnamate strongly inhibited the differentiation and migration of endothelial cells, which was further confirmed by the reduced level of vascular endothelial growth factor. CONCLUSION: Ethyl-p-methoxycinnamate exhibits significant anti-inflammatory potential by inhibiting pro-inflammatory cytokines and angiogenesis, thus inhibiting the main functions of endothelial cells. Thus, ethyl-p-methoxycinnamate could be a promising therapeutic agent ...

Analgesia induced by 2- or 100-Hz electroacupuncture in the rat tail-flick test depends on the anterior pretectal nucleus.

AIMS: The anterior pretectal nucleus (APtN) and electroacupuncture (EA) activate descending mechanisms to modulate nociceptive inputs in the spinal dorsal horn. This study examines qualitatively whether mechanisms in the APtN participate in the EA-induced analgesia in rats. MAIN METHODS: The tail-flick test was utilized to examine the changes produced by non-selective antagonists of serotonergic (methysergide, 37 pg), muscarinic (atropine, 10 ng) and opioid (naloxone, 10 ng) receptors; selective antagonists against µ (CTOP, 6.4 µg), δ (ICI174,864, 6.9 µg) or κ (nor-BNI, 7.3 µg); 5HT1 (methiothepin, 0.47 µg), 5HT2 (ketanserin, 5.4 µg), or 5HT3 (MDL 72222, 15.7 µg); and GABAA (bicuculline, 150 ng) receptors injected into the dorsal (d) or ventral (v) APtN on the antinociception induced by a 20-min EA applied at 2- or 100-Hz frequency to the Zusanli and Sanyinjiao acupoints. KEY FINDINGS: The 2-Hz EA-induced analgesia was blocked by naloxone, CTOP or atropine, was less intense after bicuculline, was shorter after methysergide or methiothepin in dAPtN, and was less intense after methysergide, methiothepin and bicuculline in vAPtN. The 100-Hz EA-induced analgesia was less intense after methysergide, methiothepin and CTOP in vAPtN, and remained unchanged after injection of the antagonists into the dAPtN. SIGNIFICANCE: The 2-Hz EA-induced analgesia utilizes cholinergic muscarinic, µ-opioid, GABAA and 5-HT1 mechanisms in the dAPtN and µ-opioid and 5-HT1 mechanisms in the vAPtN, while 100-Hz EA-induced analgesia utilizes µ-opioid and 5-HT1 mechanisms in the vAPtN but does not utilize them in the dAPtN.

Exercise alleviates hypoalgesia and increases the level of calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats

OBJECTIVE: The aim of this study was to evaluate the effects of treadmill training on nociceptive sensitivity and immunoreactivity to calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats. METHODS: Male Wistar rats were divided into three groups: control, diabetic and trained diabetic. Treadmill training was performed for 8 weeks. The blood glucose concentrations and body weight were evaluated 48 h after diabetes induction and every 30 days thereafter. The nociceptive sensitivity was evaluated using the tail-flick apparatus. The animals were then transcardially perfused, and the spinal cords were post-fixed, cryoprotected and sectioned in a cryostat. Immunohistochemistry for calcitonin gene-related peptide analysis was performed on the dorsal horn of the spinal cord. RESULTS: The nociceptive sensitivity analysis revealed that, compared with the control and trained diabetic animals, the latency to tail deflection on the apparatus was longer for the diabetic animals. Optical densitometry demonstrated decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord in diabetic animals, which was reversed by treadmill training. CONCLUSION: We concluded that treadmill training can alleviate nociceptive hypoalgesia and reverse decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord of diabetic animals without pharmacological treatment.

Attenuating effect of seeds of Adenanthera pavonina aqueous extract in neuropathic pain in streptozotocin-induced diabetic rats: an evidence of neuroprotective effects

The aim of present study was to investigate the attenuating effects of Adenanthera pavonina L., Leguminosae-Mimosaceae seeds aqueous extract (APSAE), in streptozotocin (STZ)-induced diabetic neuropathy in rats. APSAE (50, 100 and 200 mg/kg per day) was given to diabetic rats for twelve weeks. Cold and hot water tail immersion tests, photoactometer and Rota-rod tests were performed to assess degree of colder, thermal, spontaneous motor activity and motor co-ordination changes respectively at different time intervals i.e., week 0, 4, 8 and 12. Tissue superoxide anion and total calcium levels were determined after twelve weeks to assess biochemical alterations. Histopathological evaluations of sciatic nerve were also performed to assess nerve damage. APSAE treatment increased tail flick latency significantly in diabetic rats. APSAE also reduced superoxide anion and total calcium levels. These results suggested that APSAE has attenuated development of diabetic neuropathy in streptozotocin-induced diabetic rats when compared with pregabalin (10 mg/kg, p.o.) and could be beneficial in preventing the progression of diabetic nephropathy.