Evaluation of the antinociceptive effect generated by citronellal monoterpene isomers / Avaliação do efeito antinociceptivo gerado por isômeros do monoterpeno citronelal

Due to the complex nature of pain and the participation of physical, cognitive, psychological and behavioral aspects, pain management has several approaches. The use of medicinal plants in developing countries is quite expressive. Seeking new options for the treatment of emerging or debilitating diseases. Therefore, the present study seeks to elucidate the effects of the monoterpene, citronellal, differentiating its activity by isomers (R)-(+) and (S)-(-) citronellal. The study used several methods to evaluate the effects of citronellal isomers on motor coordination, nociceptive response, and the involvement of opioid, glutamatergic, and transient receptor pathways. The methods included rota-rod, hot-plate, and formalin tests, as well as the use of specific inhibitors and agonists. Data were analyzed using inferential statistics with a 95% confidence level. Both isomers did not significantly affect the motor coordination of the studied animals. The isomer (S)-(-) citronellal showed better results in relation to its structural counterpart, managing to have an antinociceptive effect in the formalin and hot plate tests with a lower concentration (100 mg/kg) and presenting fewer side effects, however, the this study was not able to elucidate the mechanism of action of this isomer despite having activity in studies with substances that act on specific targets such as glutamate and capsaicin, its activity was not reversed with the use of antagonists for pathways related to nociception. While the (R)-(+) citronellal isomer, despite showing total activity only at a concentration of 150 mg/kg, was able to determine its mechanism of action related to the opioid pathway by reversing its activity by the antagonist naloxone, being this is a pathway already correlated with nociception control treatments, however, it is also related to some unwanted side effects. In this way, new studies are sought to elucidate the mechanism related to the isomer (S)-(-) citronellal and a possibility of use in other areas related to the treatment of pain or inflammation.

Devido à natureza complexa da dor e a sua participação de aspectos físicos, cognitivos, psicológicos e comportamentais, o manejo da dor possui diversas abordagens. O uso de plantas medicinais em países em desenvolvimento é bastante expressivo. Buscando novas opções para o tratamento de denças emergentes ou debilitantes. Portanto, o presente estudo busca elucidar os efeitos do monoterpeno, citronelal, diferenciando sua atividade pelos isômeros (R)-(+) e (S)-(-) citronelal. O estudo utilizou diversos métodos para avaliar os efeitos dos isômeros de citronelal na coordenação motora, resposta nociceptiva e o envolvimento de vias opioides, glutamatérgicas e de receptores transitórios. Os métodos incluíram testes de rota-rod, placa quente e formalina, além do uso de inibidores e agonistas específicos. Os dados foram analisados estatisticamente com um intervalo de confiança de 95%. Ambos os isomeros não afetaram significativamente a coordenação motora dos animais em estudo. O isômero (S)-(-) citronelal apresentou melhores resultados em relação ao seu homólogo estrutural, conseguindo ter um efeito antinociceptivo nos testes de formalina e placa quente com menor concentração (100 mg/kg) e apresentando menos efeitos colaterais, entretanto, o presente estudo não foi capaz de elucidar o mecanismo de ação deste isomero apesar de ter atividadade em estudos com substancias que agem em alvos específicos como glutamato e capsaicina, sua atividade não foi revertida com a utilização de antagonistas para as vias relacionadas à nocicepção. Enquanto o isômero (R)-(+) citronelal, apesar de apresentar de apresentar total atividade somente na concentração de 150 mg/kg, foi capaz de determinar seu mecanismo de ação relacionado à via opióide pela reversão da sua atividade pelo antagonista naloxona, sendo esta uma via já correlacionada com os tratamentos de controle da a nocicepção, no entanto, também está relacionada a alguns efeitos colaterais indesejados. Desta forma busca-se novos estudos para elucidação do mecanismo relacionados ao isomero (S)-(-) citronellal e uma possibilidade de utilização em outras areas relacionadas ao tratamento da dor ou inflamação.

Analgesia perioperatória de gatas submetidas a ovariohisterectomia eletiva - uso preemptivo de carprofeno ou grapiprant / Perioperative analgesia in cats undergoing elective ovariohysterectomy - preemptive use of carprofen or grapiprant

Background: The nonsteroidal anti-inflammatory drugs (NSAIDs) exert their analgesic effect through peripheral inhibition of prostaglandin synthesis and a variety of other peripheral and central mechanisms. However, NSAIDs are associated with some adverse effects, mainly related to the gastrointestinal, renal, and hepatic systems, highlighting the need for research to develop safer drugs. Therefore, the aim of this study was to evaluate the efficacy of preoperative oral administration of carprofen or grapiprant in female cats submitted to elective ovariohysterectomy on the quality of perioperative analgesia and the need for hypnotic and analgesic drugs. Materials, Methods & Results: Thirty-three adult female cats were selected, without defined breed and healthy based on physical examination, routine laboratory analyses (complete blood count, total protein, Heinz body investigation and serum quantification of alanine transaminase [ALT], aspartate transaminase [AST], gamma glutamyl transpeptidase [GGT], alkaline phosphatase [ALP], urea, frutosamine, and glucose) and negative tests for feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV). After 3 days of adaptation, they were submitted to ovariohysterectomy by celiotomy and randomly allocated into 2 groups according to the preoperative drug used: GCAR [carprofen - 4 mg/kg, VO, 2 h before surgery; n = 11] and GGRA (grapiprant - 2 mg/kg IV, 2 h before surgery; n = 21]. The cats were pre-medicated with acepromazine 0.05 mg/ kg IV and later submitted to general anesthesia with propofol intravenously. Anesthesia was maintained with isoflurane in 100% oxygen. After anesthetic induction, a continuous infusion of remifentanil at a rate of 10 µg/kg/h was initiated. During the transanesthetic period, the parameters of heart rate; respiratory rate; systolic, mean, and diastolic arterial pressure using the oscillometric method; electrocardiogram; rectal temperature; partial pressure of CO2 at the end of expiration: and partial saturation of O2 in hemoglobin were continuously monitored. The evaluation of nociception was based on the changes in the aforementioned physiological parameters. The rate of remifentanil used did not change over time with the use of carprofen. However, animals that received grapiprant required a lower remifentanil dose at 20, 25, and 30 min during the procedure. The female cats that received carprofen showed an increase in mean heart rate at 30 min compared to that at 20 and 25 min. In the Grapiprant group, the heart rate at 35 min was higher only than that observed at 25 min. Discussion: The remifentanil rate did not differ between the groups, even between the times for GCAR. However, the remifentanil rate was lower from 20 min of the procedure for GGRA. This decrease may be related to a decrease in the need for anesthetics and analgesics by decreasing temperature, which causes decreases in metabolism and surgical stimulation. The increase in systolic, mean, diastolic, and heart rate arterial pressure parameters observed in both treatments after 15 min of anesthesia is related to the nociceptive stimulus resulting from traction and ligation of the ovarian pedicles and maneuvers for exteriorization of the uterus. These are considered the moments of greater surgical stimulus during ovariohysterectomy, evidenced by the greater release of cortisol and increase in physiological parameters. The results of this study show that the administration of carprofen or grapiprant was clinically similar when used preemptively for perioperative analgesia in cats submitted to elective ovariohysterectomy.

Assessment of thermal response, cardiorespiratory parameters and post-operative analgesia in dogs undergoing ovariohysterectomy with different combinations of epidural analgesia and isoflurane

This study aimed to evaluate the thermal response of the eyelids and lacrimal gland of the left eye (LETG) through infrared thermography (IRT), cardiorespiratory parameters, and their association with nociception and pain in bitches undergoing elective ovariohysterectomy (OVH) anesthetized with isoflurane and epidural analgesia. Twenty-one healthy bitches of different breeds were randomized into three groups receiving epidural blocks: GL (n=7), lidocaine (2 mg Kg-1 ); GLF (n=7), lidocaine (2 mg Kg-1 ) and fentanyl (3 µg Kg-1 ); and GLM (n=7), lidocaine (2 mg Kg-1 ) with morphine (0.1 mg Kg-1 ). IRT and cardiorespiratory parameters were evaluated at baseline (Ebasal), thirty minutes before anesthetic premedication, and at different surgical events: first incision (EInc), ligature and section of the left (ELoV), and right (ERoV) ovarian pedicle, ligature, and re-section of the cervix (EUt), and skin suture (ESut). The assessment of acute pain in the immediate post-operative period was registered at E1h, E2h, and E3h using IRT, the Dynamic Interactive Visual Analogic Scale (DIVAS), and the University of Melbourne Pain Scale (UMPS) scales. The results showed a statistically significant decrease in the lower eyelid surface temperature (LELT) during EInc for GL (32.9°C ± 0.62), in comparison to GLF (34.2°C ± 0.62) and GLM (35.3°C ± 0.62) (P = 0.006). Regarding LETG, a significant increase (P = 0.03) in the IRT of Ebasal (36.8°C ± 0.63) and EInc (36.1°C ± 0.63) for GLM was observed in comparison to the thermographic values for both perioperative events and groups. The GLM showed a significant decrease in IRT values of ERoV at E3h in the upper and lower eyelids (P = 0.03 and P = 0.01, respectively). A progressive and significant reduction of the IRT values of LETG was also recorded in GLM, with differences in ERoV (35.2 °C ± 0.63) (P = 0.02) and E3h (35.3 °C ± 0.63) (P = 0.01). The cardiovascular parameters (SAP, DAP, and MAP) did not differ between treatments, but in GL, there was a significant difference (P = 0.01) during EInc and ESut, compared to Ebasal. In the body temperature, EInc and ESut gradually decreased in all treatment groups (P = 0.01). In conclusion, hemodynamic and cardiorespiratory stability was associated with IRT readings and the absence of nociception. Changes in superficial temperature in the immediate post-operative period were lessened using isoflurane and epidural analgesia of lidocaine alone or in combination with pure opioids. These findings were clinically validated to the DIVAS and UMPS acute pain assessment scales.

Effects of ketamine, midazolam and methadone, combined with local anesthesia, in cats undergoing orchiectomy / Efeitos da cetamina, midazolam e metadona, associados à anestesia local, em gatos submetidos à orquiectomia

Different anesthetic combinations are used for orchiectomy in cats. This study aimed to evaluate the anesthetic and cardiopulmonary effects on the physiological variables of ketamine (10 mg/kg), midazolam (0.2 mg/kg) and methadone (0.3 mg/kg), combined with local anesthesia, in cats undergoing orchiectomy (n = 19 cats). The time for lateral recumbency, degree of sedation, muscle relaxation and nociception were recorded preoperatively. The propofol rescue dose was recorded. The time to head up and quality of recovery were evaluated postoperatively. The time for lateral recumbency was 5 ± 2 minu-tes. Fifteen minutes after the administration of the ketamine-midazolam-methadone combination, a greater sedative effect, muscle relaxation and less response to noxious stimulation were observed. Propofol was administered to twelve cats under local anesthesia, at a total dose of 1.5 ± 0.8 mg/kg. Surgery was started 28 ± 5 minutes after the administration of ketamine--midazolam-methadone combination. There were no differences in the physiological variables evaluated over the other evalu-ation times (p > 0.05). The recovery quality scores were adequate, and the time to head up was 51 ± 10 minutes. Under the conditions of this study, the ketamine-midazolam-methadone combination did not allow local anesthesia for orchiectomy. Many cats required propofol rescue prior to surgery. This combination promoted minimal changes in physiological variables and prolonged anesthetic recovery.(AU)

Diferentes combinações anestésicas são usadas para orquiectomia em gatos. O objetivo deste estudo foi avaliar o efeito anestésico e as alterações promovidas nas variáveis fisiológicas pela cetamina (10 mg/kg), midazolam (0.2 mg/kg) e metadona (0.3 mg/kg), combinados com anestesia local, em gatos submetidos à orquiectomia (n = 19 gatos). O tempo para adoção do decúbito lateral, grau de sedação, relaxamento muscular e nocicepção foram registrados no pré-operatório. A dose de resgate de propofol foi registrada. O tempo para o gato erguer a cabeça e a qualidade da recuperação foram avaliados no pós-operatório. O tempo para adoção do decúbito lateral foi de 5 ± 2 minutos. Quinze minutos após a administração da associação cetamina-midazolam-metadona, observou-se maior efeito sedativo e relaxamento muscular, e menor resposta à estimulação nociva. O propofol foi administrado em doze gatos para realização de anestesia local, utilizando a dose total de 1.5 ± 0.8 mg/kg. A cirurgia foi iniciada 28 ± 5 minutos após a administração de cetamina-midazolam-metadona. Não houve diferença nas variáveis fisiológicas avaliadas em relação aos demais tempos de avaliação (p > 0.05). Os escores de qualidade de recuperação foram adequados e o tempo para o gato erguer a cabeça foi de 51 ± 10 minutos. Nas condições deste estudo, cetamina-midazolam-metadona não permitiu a realização da anestesia local para orquiectomia. Muitos gatos precisaram de resgate com propofol antes de iniciar a cirurgia. Essa associação promoveu alterações mínimas nas variáveis fisiológicas e longa recuperação anestésica.(AU)

Celecoxib in the treatment of orofacial pain and discomfort in rats subjected to a dental occlusal interference model

Purpose: To evaluate the effect of a selective cyclooxygenase 2 (COX-2) inhibitor on trigeminal ganglion changes and orofacial discomfort/nociception in rats submitted to an experimental model of dental occlusal interference (DOI). Methods: Female Wistar rats (180-200 g) were divided into five groups: a sham group (without DOI) (n=15); and four experimental groups with DOI treated daily with 0.1 mL/kg saline (DOI+SAL), 8, 16, or 32 mg/kg celecoxib (DOI+cel -8, -16, -32) (n=30/group). The animals were euthanized after one, three, and seven days. The bilateral trigeminal ganglia were analyzed histomorphometrically (neuron cell body area) and immunohistochemically (COX-2, nuclear factor-kappa B [NFkB], and peroxisome proliferator-activated receptor-y [PPARy]). A bilateral nociception assay of the masseter muscle was performed. The number of bites/scratches, weight, and grimace scale scores were determined daily. One-way/two-way analysis of variance (ANOVA)/Bonferroni post hoc tests were used (P < .05, GraphPad Prism 5.0). Results: DOI+SAL showed a reduction in neuron cell body area bilaterally, whereas DOI+cel-32 exhibited a significative increase in neuron cell body area compared with DOI+SAL group (P < 0.05). The ipsilateral (P=0.007 and P=0.039) and contralateral (P < 0.001 and P=0.005) overexpression of COX-2 and NFkB and downregulation of PPARy (P=0.016 and P < 0.001) occurred in DOI+SAL, but DOI+cel-32 reverted this alteration. DOI+SAL showed increase in isplateral (P < 0.001) and contralateral (P < 0.001) nociception, an increased number of bites (P=0.010), scratches (P < 0.001), and grimace scores (P=0.032). In the group of DOI+cel-32, these parameters were reduced. Conclusions: Celecoxib attenuated DOI-induced transitory nociception/orofacial discomfort resulting from trigeminal COX-2 overexpression.

Uso do carprofeno associado aos glicosaminoglicanos em cães com osteoartrite / Use of carprofen associated with glycosaminoglycans in dogs with osteoarthritis

O presente trabalho avaliou os efeitos analgésicos do carprofeno associado ou não à condroitina com glicosamina no tratamento de 26 cães com osteoartrite, distribuídos nos grupos: GT ­ carprofeno (Carproflan®); GTP ­ carprofeno e glicosaminoglicanos (Carproflan® e Procart®); e GC ­ somente analgésico (dipirona). A evolução dos pacientes foi classificada na escala de claudicação no dia do primeiro atendimento e aos 7, 14 e 21 dias. No GT, 60% dos animais apresentou melhora clínica a partir do 7º dia, 30% não alterou seu escore de claudicação e 10% apresentou êmese a partir do 7º dia, com suspensão da medicação. No GTP, 60% dos animais apresentou melhora clínica a partir do 7º dia, 30% não alterou seu escore de claudicação, 5% apresentou êmese a partir do 7º dia e 5% a partir do 14º dia, com suspensão da medicação. No GC, nenhum animal apresentou melhora clínica. Conclui-se que os animais submetidos ao tratamento com carprofeno apresentaram melhora na claudicação, principalmente quando associado aos glicosaminoglicanos.(AU)

The analgesic effects of carprofen associated or not with chondroitin with glucosamine were evaluated in the treatment of 26 dogs with osteoarthritis, distributed into groups: TG ­ carprofen (Carproflan®); PTG ­ carprofen and glycosaminoglycans (Carproflan® and Procart®); and CG ­ only analgesic (dipyrone). The evolution of patients was classified on the lameness scale on the first day of care and at 7, 14 and 21 days. In the TG, 60% of the animals showed clinical improvement from the 7th day, 30% did not change their lameness score and 10% had emesis from the 7th day, with discontinuation of the medication. In the PTG, 60% of the animals showed clinical improvement from the 7th day, 30% did not change their lameness score, 5% had emesis from the 7th day and 5% from the 14th day, with discontinuation of the medication. In the CG, no animal showed clinical improvement. It was concluded that animals undergoing treatment with carprofen showed improvement in lameness, especially when associated with glycosaminoglycans.(AU)

Focal spinal hyperesthesia as a prognostic factor in paraplegic dogs without deep pain perception / Hiperestesia espinhal focal como fator prognóstico em cães paraplégicos sem percepção de dor profunda

Intervertebral disc extrusion (IVDE) is the most common cause of spinal cord compression in dogs, whose prognosis is variable and depends on several factors, with deep pain perception (DPP) being the main parameter used. Investigations of new prognostic factors are studied to assist in the estimation of functional recovery. Thus, this study aimed to evaluate whether spinal hyperesthesia (SH) at the compression site can be used as a prognostic factor for the functional recovery of dogs with acute IVDE (Hansen type I), without DPP being subjected to thoracolumbar hemilaminectomy. Decompression surgery was performed on the same day or the day after admission. The duration of the loss of DPP until surgery performance ranged from 1 to 60 days, with a median of 4.5 days for the group of dogs with SH and 5.5 days for those without SH. Among the 68 dogs included in this retrospective study, 73.5% (50/68) showed SH, and 26.5% (18/68) were not identified. Recovery was satisfactory in 60% (30/50) of dogs with SH and in 27.7% (5/18) of dogs without SH, demonstrating that paraplegic dogs without DPP but with SH were 3.9 times more likely to recover when compared to dogs in the same condition, but with no SH. No studies have evaluated SH by palpation of the spine as a prognostic factor, which reinforces the relevance of the present study. The results of this study imply that SH in paraplegic dogs affected by thoracolumbar IVDE, without the presence of DPP, can be used as a possible prognostic indicator of functional recovery.

A extrusão do disco intervertebral (EDIV) é a causa mais comum de lesão compressiva na medula espinhal de cães, cujo prognóstico é variável e depende de diversos fatores, sendo a percepção de dor profunda (PDP) o principal parâmetro utilizado. Pesquisas de novos fatores prognósticos são estudados com intuito de auxiliar na estimativa mais precisa de recuperação funcional. Com isso, o objetivo do estudo foi avaliar se a hiperestesia espinhal (HE) no local da compressão, pode ser utilizada como um fator prognóstico para recuperação funcional de cães com extrusão aguda do disco intervertebral (Hansen tipo I), sem a presença de PDP submetidos a hemilaminectomia toracolombar. A cirurgia descompressiva ocorreu no mesmo dia ou no dia seguinte ao atendimento. A duração da perda de dor profunda até a realização da cirurgia variou de 1 a 60 dias, com uma mediana de 4,5 dias para o grupo de cães com e 5,5 dias para aqueles sem hiperestesia espinhal. Dos 68 cães incluídos nesse estudo retrospectivo, 73,5% (50/68) apresentavam HE e, em 26,5% (18/68) a dor não foi identificada. A recuperação foi satisfatória nos cães com HE em 60% (30/50) e, sem HE, em 27,7% (5/18) dos casos, demonstrando que os cães paraplégicos sem PDP, mas com presença de hiperestesia espinhal tem 3,9 vezes mais chances de recuperação quando comparado com cães na mesma condição, mas sem HE. Não foram encontrados trabalhos que avaliaram a HE mediante a palpação da coluna vertebral como um fator prognóstico, o que reforça a relevância do presente estudo. Os resultados do presente trabalho sugerem que a HE em cães paraplégicos acometidos por EDIV toracolombar sem presença de PDP pode ser utilizada como um possível indicador prognóstico de recuperação funcional.

Antinociceptive and anti-inflammatory activities of Hymenaea martiana Hayne (Fabaceae) in mice

Abstract Hymenaea martiana is a species popularly known in Northeastern Brazil as jatobá and used in folk medicine to treat pain and inflammation. The aim of this work was to evaluate the antinociceptive and anti-inflammatory activity of H. martiana. In the present study, we carried out an investigation about the effects of the crude ethanolic extract (Hm-EtOH) and the ethyl acetate fraction (Hm-AcOEt) in models of nociception and inflammation in mice. Chemical (acetic acid-induced writhing and formalin) and thermal stimuli (hot plate) were used for the evaluation of antinociceptive activity, while for the anti-inflammatory profile paw edema induced by carrageenan was used, along with leukocyte migration to the peritoneal cavity. The presence of the flavonoid astilbin in the samples was characterized through HPLC-DAD-MS analysis. Hm-EtOH and Hm-AcOEt (100, 200 and 400 mg.kg-1, i.p.) significantly reduced the number of abdominal contortions and decreased the paw licking time in the formalin test. In the hot plate, the extract increased the latency time of animals. Hm-EtOH and Hm-AcOEt inhibited significantly the increase in the edema after the administration of carrageenan. Hm-EtOH and Hm-AcOEt inhibited leukocyte migration in the peritonitis test. HPLC-DAD-MS analysis of Hm-EtOH and Hm-AcOEt revealed the presence of the flavonoid astilbin in the samples. According to the results of this study, both Hm-EtOH and Hm-AcOEt have antinociceptive and anti-inflammatory activities, which could be related with the presence of flavonoid in the extracts. The results reinforce the popular use of this plant.

Resumo Hymenaea martiana é uma espécie popularmente conhecida no Nordeste do Brasil como jatobá e usada na medicina popular para tratar a dor e a inflamação. O objetivo deste trabalho foi avaliar a atividade antinociceptiva e anti-inflamatória de H. martiana. No presente estudo, foram avaliados os efeitos do extrato etanólico bruto (Hm-EtOH) e da fração acetato de etila (Hm-AcOEt) em modelos de nocicepção e inflamação em camundongos. Foram utilizados estímulos químicos (contorções abdominais induzidas por ácido acético e teste da formalina) e estímulo térmico (teste da placa quente) para avaliação da atividade antinociceptiva, enquanto no perfil anti-inflamatório foi utilizado o teste do edema de pata induzido por carragenina e migração de leucócitos para a cavidade peritoneal. A presença do flavonoide astilbina nas amostras foi caracterizada através de análise por CLAE-DAD-EM. Hm-EtOH e o Hm-AcOEt (100, 200 e 400 mg.kg-1, i.p.) reduziram significativamente o número de contorções abdominais e diminuíram o tempo de lambida da pata no teste da formalina. No teste da placa quente, houve aumento do tempo de latência dos animais. Hm-EtOH e Hm-AcOEt inibiram significativamente o aumento do edema após a administração de carragenina, bem como inibiram a migração de leucócitos no teste de peritonite. A análise por CLAE-DAD-EM de Hm-EtOH e Hm-AcOEt revelou a presença do flavonoide astilbina nas amostras. De acordo com os resultados deste estudo, tanto Hm-EtOH quanto o Hm-AcOEt possuem atividades antinociceptiva e anti-inflamatória, o que pode estar relacionado à presença do flavonoide. Os resultados reforçam o uso popular desta planta.

Antinociceptive and anti-inflammatory activities of Hymenaea martiana Hayne (Fabaceae) in mice / Atividade antinociceptiva e anti inflamatória de Hymenaea martiana Hayne (Fabaceae) em camundongos

Hymenaea martiana is a species popularly known in Northeastern Brazil as "jatobá" and used in folk medicine to treat pain and inflammation. The aim of this work was to evaluate the antinociceptive and anti-inflammatory activity of H. martiana. In the present study, we carried out an investigation about the effects of the crude ethanolic extract (Hm-EtOH) and the ethyl acetate fraction (Hm-AcOEt) in models of nociception and inflammation in mice. Chemical (acetic acid-induced writhing and formalin) and thermal stimuli (hot plate) were used for the evaluation of antinociceptive activity, while for the anti-inflammatory profile paw edema induced by carrageenan was used, along with leukocyte migration to the peritoneal cavity. The presence of the flavonoid astilbin in the samples was characterized through HPLC-DAD-MS analysis. Hm-EtOH and Hm-AcOEt (100, 200 and 400 mg.kg-¹, i.p.) significantly reduced the number of abdominal contortions and decreased the paw licking time in the formalin test. In the hot plate, the extract increased the latency time of animals. Hm-EtOH and Hm-AcOEt inhibited significantly the increase in the edema after the administration of carrageenan. Hm-EtOH and Hm-AcOEt inhibited leukocyte migration in the peritonitis test. HPLC-DAD-MS analysis of Hm-EtOH and Hm-AcOEt revealed the presence of the flavonoid astilbin in the samples. According to the results of this study, both Hm-EtOH and Hm-AcOEt have antinociceptive and anti-inflammatory activities, which could be related with the presence of flavonoid in the extracts. The results reinforce the popular use of this plant.

Hymenaea martiana é uma espécie popularmente conhecida no Nordeste do Brasil como “jatobᔠe usada na medicina popular para tratar a dor e a inflamação. O objetivo deste trabalho foi avaliar a atividade antinociceptiva e anti inflamatória de H. martiana. No presente estudo, foram avaliados os efeitos do extrato etanólico bruto (Hm-EtOH) e da fração acetato de etila (Hm-AcOEt) em modelos de nocicepção e inflamação em camundongos. Foram utilizados estímulos químicos (contorções abdominais induzidas por ácido acético e teste da formalina) e estímulo térmico (teste da placa quente) para avaliação da atividade antinociceptiva, enquanto no perfil anti-inflamatório foi utilizado o teste do edema de pata induzido por carragenina e migração de leucócitos para a cavidade peritoneal. A presença do flavonoide astilbina nas amostras foi caracterizada através de análise por CLAE-DAD-EM. Hm-EtOH e o Hm-AcOEt (100, 200 e 400 mg.kg-¹, i.p.) reduziram significativamente o número de contorções abdominais e diminuíram o tempo de lambida da pata no teste da formalina. No teste da placa quente, houve aumento do tempo de latência dos animais. Hm-EtOH e Hm-AcOEt inibiram significativamente o aumento do edema após a administração de carragenina, bem como inibiram a migração de leucócitos no teste de peritonite. A análise por CLAE-DAD-EM de Hm-EtOH e Hm-AcOEt revelou a presença do flavonoide astilbina nas amostras. De acordo com os resultados deste estudo, tanto Hm-EtOH quanto o Hm-AcOEt possuem atividades antinociceptiva e anti-inflamatória, o que pode estar relacionado à presença do flavonoide. Os resultados reforçam o uso popular desta planta.

Antinociceptive and anti-inflammatory activities of Hymenaea martiana Hayne (Fabaceae) in mice / Atividade antinociceptiva e anti-inflamatória de Hymenaea martiana Hayne (Fabaceae) em camundongos

Hymenaea martiana is a species popularly known in Northeastern Brazil as "jatobá" and used in folk medicine to treat pain and inflammation. The aim of this work was to evaluate the antinociceptive and anti-inflammatory activity of H. martiana. In the present study, we carried out an investigation about the effects of the crude ethanolic extract (Hm-EtOH) and the ethyl acetate fraction (Hm-AcOEt) in models of nociception and inflammation in mice. Chemical (acetic acid-induced writhing and formalin) and thermal stimuli (hot plate) were used for the evaluation of antinociceptive activity, while for the anti-inflammatory profile paw edema induced by carrageenan was used, along with leukocyte migration to the peritoneal cavity. The presence of the flavonoid astilbin in the samples was characterized through HPLC-DAD-MS analysis. Hm-EtOH and Hm-AcOEt (100, 200 and 400 mg.kg-1, i.p.) significantly reduced the number of abdominal contortions and decreased the paw licking time in the formalin test. In the hot plate, the extract increased the latency time of animals. Hm-EtOH and Hm-AcOEt inhibited significantly the increase in the edema after the administration of carrageenan. Hm-EtOH and Hm-AcOEt inhibited leukocyte migration in the peritonitis test. HPLC-DAD-MS analysis of Hm-EtOH and Hm-AcOEt revealed the presence of the flavonoid astilbin in the samples. According to the results of this study, both Hm-EtOH and Hm-AcOEt have antinociceptive and anti-inflammatory activities, which could be related with the presence of flavonoid in the extracts. The results reinforce the popular use of this plant.

Hymenaea martiana é uma espécie popularmente conhecida no Nordeste do Brasil como "jatobá" e usada na medicina popular para tratar a dor e a inflamação. O objetivo deste trabalho foi avaliar a atividade antinociceptiva e antiinflamatória de H. martiana. No presente estudo, foram avaliados os efeitos do extrato etanólico bruto (Hm-EtOH) e da fração acetato de etila (Hm-AcOEt) em modelos de nocicepção e inflamação em camundongos. Foram utilizados estímulos químicos (contorções abdominais induzidas por ácido acético e teste da formalina) e estímulo térmico (teste da placa quente) para avaliação da atividade antinociceptiva, enquanto no perfil anti-inflamatório foi utilizado o teste do edema de pata induzido por carragenina e migração de leucócitos para a cavidade peritoneal. A presença do flavonoide astilbina nas amostras foi caracterizada através de análise por CLAE-DAD-EM. Hm-EtOH e o Hm-AcOEt (100, 200 e 400 mg.kg-1, i.p.) reduziram significativamente o número de contorções abdominais e diminuíram o tempo de lambida da pata no teste da formalina. No teste da placa quente, houve aumento do tempo de latência dos animais. Hm-EtOH e Hm-AcOEt inibiram significativamente o aumento do edema após a administração de carragenina, bem como inibiram a migração de leucócitos no teste de peritonite. A análise por CLAE-DAD-EM de Hm-EtOH e Hm-AcOEt revelou a presença do flavonoide astilbina nas amostras. De acordo com os resultados deste estudo, tanto Hm-EtOH quanto o Hm-AcOEt possuem atividades antinociceptiva e anti-inflamatória, o que pode estar relacionado à presença do flavonoide. Os resultados reforçam o uso popular desta planta.

Empiema epidural espinhal em gato com suspeita de linfoma em canal vertebral / Spinal epidural empyema in a cat with suspect of spinal canal lymphoma

Background: Spinal epidural empyema (SEE) is a rare disease in cats that has been described as a cause of severe compressive myelopathy. It is characterized by accumulation of purulent exudate in the form of an abscess in the epidural space. Neurological signs range from spinal hyperesthesia to rapidly progressive paraplegia and may be associated with systemic signs. Spinal lymphoma is the most common neoplasm affecting the central nervous system of cats and can mimic different neoplasms and non-neoplastic diseases, such as SEE. The aim of this study is to report a case of SEE in a cat and highlight the similarities in neurological, laboratory, and imaging findings between this disease and spinal lymphoma. Case: A 8-month-old male neutered mixed-breed cat was referred to the Veterinary Medical Teaching Hospital (HVU) of the UFSM with acute, non-progressive paraplegia. On neurological examination, the patient was paraplegic with no nociception, normal spinal reflexes, increased muscle tone in the pelvic limbs, absence of cutaneous trunci reflex, and spinal hyperesthesia between T13-L1, demonstrating injury in the T3-L3 spinal cord segment. The differential diagnoses included acute spinal cord trauma, neoplasm (lymphoma), and infectious diseases. Hemogram showed lymphocytosis (8062/µL); the biochemical examinations were unremarkable. Tests for antibodies against feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) antigens were negative. Simple radiography, abdominal ultrasonography, and cerebrospinal fluid findings were also normal. Myelography showed left dorsolateral extradural spinal cord compression from T12 to L1. Based on these findings, the presumptive diagnosis was spinal lymphoma and chemotherapy was initiated. After 2 days, the animal began to show hyporexia, adipsia, vomiting, and diarrhea, in addition to an increase in subcutaneous volume in the thoracolumbar region. Antibiotic therapy was initiated; however, the patient died. Necropsy revealed an abscess in the left dorsolateral extradural space at T12-T13 and T13-L1. Bacterial cultures revealed the presence of Neisseria spp. that was resistant to various antibiotics. On the basis of these findings, the animal was diagnosed with SEE. Discussion: This case report aims to inform veterinarians about the diagnosis of SEE. SEE is a rare condition in cats compared to spinal lymphoma; however, their presentation is similar. Even in imaging examinations, such as magnetic resonance imaging, it is not possible to differentiate between these 2 conditions. The evolution of clinical signs made the diagnosis of the present case difficult since it was acute and not progressive. All cases of SEE reported in the literature were progressive, acute, or chronic. Although testing for FeLV was negative, only 56% of cats with spinal lymphoma test positive for this virus. Clinical signs reported by the owner after the start of chemotherapy may be related to adverse effects, such as immunosuppression, which led to worsening of the condition, culminating in the appearance of a subcutaneous abscess. Subsequently, SEE was suspected; however, surgical decompression was not performed as the animal died soon after. The authors of this report reinforce the need for a definitive and non-presumptive diagnosis of spinal lymphoma to initiate chemotherapy because it mimics different neoplasms and non-neoplastic diseases, such as SEE. Surgical removal of the compressive mass in the spinal cord and histopathological analyses are necessary.

Antinociceptive and anti-inflammatory activities of Hymenaea martiana Hayne (Fabaceae) in mice / Atividade antinociceptiva e anti inflamatória de Hymenaea martiana Hayne (Fabaceae) em camundongos

Hymenaea martiana is a species popularly known in Northeastern Brazil as "jatobá" and used in folk medicine to treat pain and inflammation. The aim of this work was to evaluate the antinociceptive and anti-inflammatory activity of H. martiana. In the present study, we carried out an investigation about the effects of the crude ethanolic extract (Hm-EtOH) and the ethyl acetate fraction (Hm-AcOEt) in models of nociception and inflammation in mice. Chemical (acetic acid-induced writhing and formalin) and thermal stimuli (hot plate) were used for the evaluation of antinociceptive activity, while for the anti-inflammatory profile paw edema induced by carrageenan was used, along with leukocyte migration to the peritoneal cavity. The presence of the flavonoid astilbin in the samples was characterized through HPLC-DAD-MS analysis. Hm-EtOH and Hm-AcOEt (100, 200 and 400 mg.kg-¹, i.p.) significantly reduced the number of abdominal contortions and decreased the paw licking time in the formalin test. In the hot plate, the extract increased the latency time of animals. Hm-EtOH and Hm-AcOEt inhibited significantly the increase in the edema after the administration of carrageenan. Hm-EtOH and Hm-AcOEt inhibited leukocyte migration in the peritonitis test. HPLC-DAD-MS analysis of Hm-EtOH and Hm-AcOEt revealed the presence of the flavonoid astilbin in the samples. According to the results of this study, both Hm-EtOH and Hm-AcOEt have antinociceptive and anti-inflammatory activities, which could be related with the presence of flavonoid in the extracts. The results reinforce the popular use of this plant.(AU)

Hymenaea martiana é uma espécie popularmente conhecida no Nordeste do Brasil como “jatobᔠe usada na medicina popular para tratar a dor e a inflamação. O objetivo deste trabalho foi avaliar a atividade antinociceptiva e anti inflamatória de H. martiana. No presente estudo, foram avaliados os efeitos do extrato etanólico bruto (Hm-EtOH) e da fração acetato de etila (Hm-AcOEt) em modelos de nocicepção e inflamação em camundongos. Foram utilizados estímulos químicos (contorções abdominais induzidas por ácido acético e teste da formalina) e estímulo térmico (teste da placa quente) para avaliação da atividade antinociceptiva, enquanto no perfil anti-inflamatório foi utilizado o teste do edema de pata induzido por carragenina e migração de leucócitos para a cavidade peritoneal. A presença do flavonoide astilbina nas amostras foi caracterizada através de análise por CLAE-DAD-EM. Hm-EtOH e o Hm-AcOEt (100, 200 e 400 mg.kg-¹, i.p.) reduziram significativamente o número de contorções abdominais e diminuíram o tempo de lambida da pata no teste da formalina. No teste da placa quente, houve aumento do tempo de latência dos animais. Hm-EtOH e Hm-AcOEt inibiram significativamente o aumento do edema após a administração de carragenina, bem como inibiram a migração de leucócitos no teste de peritonite. A análise por CLAE-DAD-EM de Hm-EtOH e Hm-AcOEt revelou a presença do flavonoide astilbina nas amostras. De acordo com os resultados deste estudo, tanto Hm-EtOH quanto o Hm-AcOEt possuem atividades antinociceptiva e anti-inflamatória, o que pode estar relacionado à presença do flavonoide. Os resultados reforçam o uso popular desta planta.(AU)

Venom of the giant ant Dinoponera quadriceps attenuates inflammatory pain in mouse cutaneous wound healing model

Arthropod venoms are potential sources of bioactive substances, providing tools for the validation of popular use and new drugs design. Ants belonging to the genus Dinoponera are used in the folk medicine to treat inflammatory conditions. It was previously demonstrated that the venom of the giant ant Dinoponera quadriceps (DqV), containing a mixture of polypeptides, elicit antinociceptive effect in mice models of chemical, mechanical and thermal nociception. The aim of this study was to evaluate DqV antiinflammatory and antihypernociceptive effects in a mice model of traumatic cutaneous wound. Colonies of D. quadriceps were collected in the 'Serra de Maranguape' (State of Ceará, northeastern Brazil), a small mountain range located on the coastal zone, and the venom secreted by the ant glands was extracted with capillary tubes, further lyophilized and maintained at -20 ± 1ºC until use. Wounds were performed in the dorsum of Swiss mice. Animals received intravenous (i.v.) injection of DqV (50 µg kg-1 day-1) during 3 days for evaluation of inflammatory parameters present in the wounds: hypernociception, leukocyte infiltrate, myeloperoxidase activity, nitrite/nitrate content. Data was tested by two-way ANOVA and Bonferroni's post-hoc test. DqV reduced (2.7 folds) hypernociception at 48 hours, leukocyte infiltration by 65% at 6 hours and myeloperoxidase activity by 60% at 0.5 hour after wound induction. In conclusion, the venom extracted from D. quadriceps glands attenuates inflammation and hypernociception in mice cutaneous wounds.(AU)

Quality of death in the river buffalo (Bubalus bubalis)

Results on appropriate, inappropriate, and painful slaughtering methods of river buffalo (Bubalus bubalis) are discussed. Undesirable consequences of poor desensitization and/or slaughtering procedures, causing pain and suffering to animals, are also approached. These considerations are relevant as unsuitable methods can reduce consumer acceptance and commercial value of the meat obtained from animals undergoing deficient slaughtering procedures due to a lack of concern regarding their welfare. Relevant databases –Scopus, Science Direct, and PubMedwere searched for this review, including keywords such as pain, slaughter, stunning, Bubalus bubalis, and animal welfare. A detailed description of river buffalo's encephalic anatomy was compared to cattle concerning correct stunning and slaughter methods. The neurobiological processes of pain felt by animals when inadequately desensitized was also examined. Finally, recent findings on stunning methods for buffaloes were discussed, including encephalography. It was concluded that different animal species may require different stunning methods; at the same time, the optimal anatomical site also varies between species. Therefore, it is of the utmost importance to train the personnel performing these procedures (transport, stunning, slaughtering) to avoid mishandling that jeopardizes animal welfare by generating stimuli that trigger neurophysiological responses and, in turn, translate into pain during slaughter and reduced meat quality.(AU)

Quality of death in the river buffalo (Bubalus bubalis)

Results on appropriate, inappropriate, and painful slaughtering methods of river buffalo (Bubalus bubalis) are discussed. Undesirable consequences of poor desensitization and/or slaughtering procedures, causing pain and suffering to animals, are also approached. These considerations are relevant as unsuitable methods can reduce consumer acceptance and commercial value of the meat obtained from animals undergoing deficient slaughtering procedures due to a lack of concern regarding their welfare. Relevant databases –Scopus, Science Direct, and PubMedwere searched for this review, including keywords such as pain, slaughter, stunning, Bubalus bubalis, and animal welfare. A detailed description of river buffalo's encephalic anatomy was compared to cattle concerning correct stunning and slaughter methods. The neurobiological processes of pain felt by animals when inadequately desensitized was also examined. Finally, recent findings on stunning methods for buffaloes were discussed, including encephalography. It was concluded that different animal species may require different stunning methods; at the same time, the optimal anatomical site also varies between species. Therefore, it is of the utmost importance to train the personnel performing these procedures (transport, stunning, slaughtering) to avoid mishandling that jeopardizes animal welfare by generating stimuli that trigger neurophysiological responses and, in turn, translate into pain during slaughter and reduced meat quality.(AU)

Quality of death in the river buffalo (Bubalus bubalis)

Results on appropriate, inappropriate, and painful slaughtering methods of river buffalo (Bubalus bubalis) are discussed. Undesirable consequences of poor desensitization and/or slaughtering procedures, causing pain and suffering to animals, are also approached. These considerations are relevant as unsuitable methods can reduce consumer acceptance and commercial value of the meat obtained from animals undergoing deficient slaughtering procedures due to a lack of concern regarding their welfare. Relevant databases –Scopus, Science Direct, and PubMed– were searched for this review, including keywords such as pain, slaughter, stunning, Bubalus bubalis, and animal welfare. A detailed description of river buffalo's encephalic anatomy was compared to cattle concerning correct stunning and slaughter methods. The neurobiological processes of pain felt by animals when inadequately desensitized was also examined. Finally, recent findings on stunning methods for buffaloes were discussed, including encephalography. It was concluded that different animal species may require different stunning methods; at the same time, the optimal anatomical site also varies between species. Therefore, it is of the utmost importance to train the personnel performing these procedures (transport, stunning, slaughtering) to avoid mishandling that jeopardizes animal welfare by generating stimuli that trigger neurophysiological responses and, in turn, translate into pain during slaughter and reduced meat quality.

Reproductive ecology and territorial behavior of Boana goiana (Anura: Hylidae), a gladiator frog from the Brazilian Cerrado

Anuran males and females adopt different reproductive and behavioral strategies in different contexts. We investigated the reproductive ecology and territorial behavior of the treefrog Boana goiana (B. Lutz, 1968) from the Brazilian Cerrado. We hypothesized that competitor density/proximity would increase the behavioral responses of B. goiana males, and that mating would be assortative. We also tested if the number of eggs correlates with female size and if there is a trade-off between clutch size and egg size. We conducted two territoriality experiments to test the effects of male size, competitor proximity and competitor density. Larger males called more in the presence of a second male. In the second experiment, the largest males emitted more calls and the distance to the nearest male increased as resident males called more. In both experiments, the number of calls was influenced by either male size or spacing between males. Some males behaved as satellites, probably to avoid fights. Our analyses indicate that females choose males with similar sizes to their own, corroborating our hypothesis of size-assortative mating. We found no relationships between female size and clutch size/volume, and between egg size and number of eggs per clutch. We also report multiple spawning for this species. The low incidence of physical combats and the spacing pattern indicate that this species relies almost solely on calls to resolve contests, which could be explained by low motivation, or simply because males avoid combats to decrease injury risks. Thus, acoustic or even multimodal communication seems crucial for social interactions of B. goiana.(AU)

Pathophysiology of pain and use of opioids in cattle / Fisiopatogenia da dor e uso de opioides em bovinos / Fisiopatología del dolor y uso de opioides en bovinos

O controle da dor é uma área que atualmente vem ganhando grande importância, principalmente para a bovinocultura. Determinar a origem e as causas do processo doloroso é uma tarefa que demanda grande atenção por parte dos profissionais, especialmente para que possam intervir da melhor maneira possível, além de buscar remover os fatores que incitaram, atuar na prevenção e tratamento do mecanismo da dor com uso de diversos fármacos disponíveis no mercado. O uso de opioides vem sendo alvo de estudos como estratégia farmacológica para controle e manejo do sofrimento animal, fato este que induz graves perdas e prejuízos para a produção bovina, a nível produtivo, reprodutivo e econômico. No entanto, faz-se necessário cada vez mais novos estudos a respeito dos benefícios que eles podem proporcionar aos bovinos, uma vez que existem alguns limitantes como custo e efeitos adversos.

Pain control is an area that is currently gaining great importance, mainly for beef production. Determining the origin and causes of the painful process is a task that demands great attention from professionals, especially so that they can intervene in the best possible way. In addition to seeking to remove the factors that prompted them, they act in the prevention and treatment of the pain mechanism with the use of various drugs available on the market. The use of opioids has been the subject of studies as a pharmacological strategy for the control and management of animal suffering, a fact that induces serious losses and losses for bovine production, at the productive, reproductive and economic level. However, more and more studies are needed regarding the benefits they can provide to cattle, since there are some limitations such as cost and adverse effects.

El control del dolor es un área que está cobrando gran importancia en la actualidad, especialmente para la ganadería. Determinar el origen y las causas del proceso doloroso es una tarea que requiere una gran atención por parte de los profesionales, especialmente para que puedan intervenir de la mejor manera posible, además de buscar remover los factores que los incitaron, actuando en la prevención y tratamiento del mecanismo del dolor mediante el uso de diversos fármacos disponibles en el mercado. El uso de opioides ha sido objeto de estudios como estrategia farmacológica para el control y manejo del sufrimiento animal, hecho que induce graves pérdidas y pérdidas para la producción bovina, a nivel productivo, reproductivo y económico. Sin embargo, se necesitan cada vez más estudios sobre los beneficios que pueden brindar al ganado, ya que existen algunas limitaciones como el costo y los efectos adversos.

Effects of parasites and predators on nociception: decreases analgesia reduces overwinter survival in root voles (Rodentia: Cricetidae)

Growing evidence suggests that parasite-infected prey is more vulnerable to predation. However, the mechanism underlying this phenomenon is obscure. In small mammals, analgesia induced by environmental stressors is a fundamental component of the defensive repertoire, promoting defensive responses. Thus, the reduced analgesia may impair the defensive ability of prey and increase their predation risk. This study aimed to determine whether coccidia infection increases the vulnerability to predation in root voles, Microtus oeconomus (Pallas, 1776), by decreased analgesia. Herein, a predator stimulus and parasitic infection were simulated in the laboratory via a two-level factorial experiment, then, the vole nociceptive responses to an aversive thermal stimulus were evaluated. Further, a field experiment was performed to determine the overwinter survival of voles with different nociceptive responses via repeated live trapping. The coccidia-infected voles demonstrated reduced predator-induced analgesia following exposure to predator odor. Meanwhile, pain-sensitive voles had lower overwinter survival than pain-inhibited voles in enclosed populations throughout the duration of the experiment. Our findings suggest that coccidia infection attenuates predator-induced analgesia, resulting in an increased vulnerability to predation.(AU)

Pathophysiology of pain and use of opioids in cattle / Fisiopatogenia da dor e uso de opioides em bovinos / Fisiopatología del dolor y uso de opioides en bovinos

O controle da dor é uma área que atualmente vem ganhando grande importância, principalmente para a bovinocultura. Determinar a origem e as causas do processo doloroso é uma tarefa que demanda grande atenção por parte dos profissionais, especialmente para que possam intervir da melhor maneira possível, além de buscar remover os fatores que incitaram, atuar na prevenção e tratamento do mecanismo da dor com uso de diversos fármacos disponíveis no mercado. O uso de opioides vem sendo alvo de estudos como estratégia farmacológica para controle e manejo do sofrimento animal, fato este que induz graves perdas e prejuízos para a produção bovina, a nível produtivo, reprodutivo e econômico. No entanto, faz-se necessário cada vez mais novos estudos a respeito dos benefícios que eles podem proporcionar aos bovinos, uma vez que existem alguns limitantes como custo e efeitos adversos.(AU)

Pain control is an area that is currently gaining great importance, mainly for beef production. Determining the origin and causes of the painful process is a task that demands great attention from professionals, especially so that they can intervene in the best possible way. In addition to seeking to remove the factors that prompted them, they act in the prevention and treatment of the pain mechanism with the use of various drugs available on the market. The use of opioids has been the subject of studies as a pharmacological strategy for the control and management of animal suffering, a fact that induces serious losses and losses for bovine production, at the productive, reproductive and economic level. However, more and more studies are needed regarding the benefits they can provide to cattle, since there are some limitations such as cost and adverse effects.(AU)

El control del dolor es un área que está cobrando gran importancia en la actualidad, especialmente para la ganadería. Determinar el origen y las causas del proceso doloroso es una tarea que requiere una gran atención por parte de los profesionales, especialmente para que puedan intervenir de la mejor manera posible, además de buscar remover los factores que los incitaron, actuando en la prevención y tratamiento del mecanismo del dolor mediante el uso de diversos fármacos disponibles en el mercado. El uso de opioides ha sido objeto de estudios como estrategia farmacológica para el control y manejo del sufrimiento animal, hecho que induce graves pérdidas y pérdidas para la producción bovina, a nivel productivo, reproductivo y económico. Sin embargo, se necesitan cada vez más estudios sobre los beneficios que pueden brindar al ganado, ya que existen algunas limitaciones como el costo y los efectos adversos.(AU)