Comparative study between S-(+)-ketamine­midazolam and fentanyl­droperidol in black-tufted marmosets (Callithrix penicillata) / Estudo comparativo entre S-(+)cetamina-midazolam e fentanil-droperidol em saguis-de-tufo-preto (Callithrix penicillata)

Sedative and antinociceptive effects of two anesthetic protocols in black-tufted marmosets were compared in this study. Twenty-six marmosets underwent chemical immobilization for physical examination, blood sampling, tattooing, and microchipping. Animals were randomly treated with S-(+)-ketamine (10 mg/kg) and midazolam (1 mg/kg) (KM) or fentanyl (12.5 µg/kg) and droperidol (625 µg/kg) (FD) given by intramuscular injection. Heart and respiratory rates were recorded. Sedation, antinociception, muscle relaxation, posture, auditory, and visual responses were evaluated using a scoring system. Sedation in KM was achieved faster (p < 0.001) and lasted for a shorter period of time (p = 0.0009). KM was similar to FD in its cardiorespiratory effects, auditory and visual responses. Both protocols promoted adequate sedation to allow manipulation. Animals in KM assumed lateral recumbency while animals in FD maintained a quadrupedal posture during evaluation. FD produced less intense sedation and muscle relaxation but a higher degree of antinociception compared to KM and is suitable for procedures that require analgesia in black-tufted marmosets.(AU)

O presente estudo comparou os efeitos cardiorrespiratórios, sedativos e antinociceptivos de dois protocolos anestésicos em saguis-de-tufo-preto (Callithrix penicillata). Vinte e seis saguis foram submetidos à contenção química para exame físico, coleta de sangue, tatuagem de identificação e microchip. Os animais foram tratados aleatoriamente com a associação de S-(+)-cetamina (10 mg/kg) e midazolam (1 mg/kg) (KM) ou fentanil (12,5 µg/kg) e droperidol (625 µg/kg) (FD), administrados por injeção intramuscular. Foram avaliadas frequência cardíaca, frequência respiratória, sedação, antinocicepção, relaxamento muscular, postura e resposta ao estímulo auditivo e visual. A sedação em KM foi alcançada mais rapidamente (p <0,001) e teve um tempo hábil mais curto (p = 0,0009). KM foi semelhante a FD nos efeitos cardiorrespiratórios, respostas auditivas e visuais. Os dois protocolos promoveram sedação adequada para manipulação. Os animais do grupo KM permaneceram em decúbito lateral durante a avaliação, enquanto os animais em FD mantiveram postura quadrupedal. FD resultou em sedação e relaxamento muscular de menor intensidade, porém com maior escore de antinocicepção em comparação com KM, sendo adequada para procedimentos que requerem analgesia em saguis-de-tufo-preto.(AU)

Caryocar villosum attenuates inflammation by inhibiting CXCL1 activation and peripheral hyperalgesia through opioid pathway modulation / Caryocar villosum atenua a inflamação ao inibir a ativação de CXCL1 e a hiperalgesia periférica por meio da modulação da via opioide

The oil of Caryocar villosum is used in Amazonian folk medicine to treat pain and inflammatory conditions. So, we assessed the anti-inflammatory and antinociceptive properties of the ethanolic extract obtained from the fruit peels of this species. The acetic acid-induced writhing, carrageenan-induced mechanical hyperalgesia, formalin, carrageenan-induced paw edema and carrageenan-induced peritonitis tests were used on mice. The C. villosum ethanolic extract significantly inhibited the number of abdominal writhes, mechanical hyperalgesia and paw licking time in the second phase of the formalin test. At a dose of 300 mg kg-1, the extract also significantly reduced the volume of edema formed in the late phase and reduced the recruitment of leukocytes and neutrophils in the peritoneal cavity, as well as CXCL1 chemokine levels. It is suggested that the extract attenuates the leukocyte recruitment by inhibiting the CXCL1 activation. The peripheral antinociceptive activity occured through opioid pathway modulation because pretreatment with C. villosum ethanolic extract reversed the naltrexone-induced antinociception.(AU)

O óleo de Caryocar villosum é usado na medicina popular amazônica para tratar dores e condições inflamatórias. Assim, avaliamos as propriedades antiinflamatórias e antinociceptivas do extrato etanólico obtido das cascas dos frutos desta espécie. Os testes de contorções induzidas por ácido acético, hiperalgesia mecânica induzida por carragenina, formalina, edema de pata induzido por carragenina e peritonite induzida por carragenina foram usados em camundongos. O extrato etanólico de C. villosum obtido das cascas dos frutos inibiu significativamente o número de contorções abdominais, a hiperalgesia mecânica e o tempo de lambida da pata na segunda fase do teste de formalina. Na dose de 300 mg kg-1, o extrato também reduziu significativamente o volume de edema formado na fase tardia e reduziu o recrutamento de leucócitos e neutrófilos na cavidade peritoneal, bem como os níveis de quimiocina CXCL1. Sugere-se que o extrato atenua o recrutamento de leucócitos por meio da inibição da ativação de CXCL1. A atividade antinociceptiva periférica ocorre por meio da modulação da via opioide pois o pré-tratamento com o extrato etanólico de C. villosum reverteu a antinocicepção induzida pela naltrexona.(AU)

Anestesia geral em jabuti-piranga (Chelonoides carbonaria) para retirada de corpo estranho gástrico / General anesthesia in red-footed tortoise (Chelonoides carbonaria) for gastric foreign body removal

Background: The anatomical, physiological, and pharmacological characteristics of reptiles make anesthesia in chelonians particularly challenging. Specific literature regarding safe anesthetic protocols that provide immobilization, antinociception, amnesia, and unconsciousness are scarce. Thus, this paper aims to report the case of a red-footed tortoise submitted to long-duration general anesthesia to celiotomy for foreign body removal. Case: An adult red-footed tortoise (Chelonoides carbonaria), 5.9 kg, was admitted due to hyporexia after ingesting a metallic fishhook. Serial radiographs confirmed the diagnosis and location of the foreign body in the stomach. The animal was premedicated with 0.03 mg/kg dexmedetomidine, 6 mg/kg ketamine, and 0.4 mg/kg butorphanol intramuscularly. After 90 min we inserted a 22G jugular catheter and proceeded to anesthesia induction with 5 mg/kg propofol. We intubated the animal with a 2.5 mm uncuffed endotracheal and started fluid therapy at a rate of 5 mL/kg/h. Surgical anesthesia was maintained with isoflurane in 0.21 oxygen, in a non-rebreathing circuit (baraka), under spontaneous breathing. Expired isoflurane was maintained between 3 and 4.5%. Due to reduced respiratory rate and hypercapnia, we opted for implementing manually-assisted positive pressure ventilation. Morphine (0.5 mg/kg) was administered at 10 and 87 min after the beginning of the surgery for further analgesia when the isoflurane requirement increased significantly. We did not detect any alterations in heart and body temperature. Surgical anesthesia lasted 6 h. During anesthesia recovery, voluntary head retraction and coordinated movement of the limbs occurred at 240 and 540 min after the extubation, respectively. In 2 days, the patient returned to voluntary feeding, being very active and responsive to stimulus. The post-surgical hematologic evaluation was unremarkable. Discussion: Pre-anesthetic medication aimed to promote sedation and preemptive analgesia. Due to its minimal cardiorespiratory depression, we chose the combination of ketamine, dexmedetomidine, and butorphanol. Dexmedetomidine reduced the ketamine dose and caused sufficient muscle relaxation and immobilization to perform the jugular catheter placement. Butorphanol is an agonist-antagonist opioid; that is why we decided to add it to the protocol for antinociception. However, due to signs of nociceptive response (increased isoflurane requirements and heart rate), and considering the evidence of a predominance of µ receptors in reptiles, we administered low-dose morphine twice during the procedure. Propofol was chosen as an induction agent at a dose sufficient to allow endotracheal intubation. Since reptilians often show apnea in the presence of 100% oxygen, we used a 0.21 oxygen fraction. Despite this, the patient showed respiratory depression. Due to right to left cardiac shunt, sudden changes in the direction of the blood can lead to very rapid changes in the serum concentrations of isoflurane, which leads to frequent oscillations in the anesthetic depth and consequently the need for vaporizer adjustments, which may justify the high expired isoflurane fraction during the procedure. Despite that, physiological parameters were maintained within normal ranges for the species, with slight variations during the surgical procedure. We conclude that the proposed anesthetic protocol is safe for long-duration anesthesia in chelonians, ensuring cardiovascular and respiratory stability. Thus, this report may help veterinarians to perform safe anesthesia in tortoises submitted to invasive surgical procedures.

Analgesic and side effects of intravenous recombinant Phα1ß

Intrathecal injection of voltage-sensitive calcium channel blocker peptide toxins exerts analgesic effect in several animal models of pain. Upon intrathecal administration, recombinant Phα1ß exerts the same analgesic effects as the those of the native toxin. However, from a clinical perspective, the intrathecal administration limits the use of anesthetic drugs in patients. Therefore, this study aimed to investigate the possible antinociceptive effect of intravenous recombinant Phα1ß in rat models of neuropathic pain, as well as its side effects on motor, cardiac (heart rate and blood pressure), and biochemical parameters. Methods: Male Wistar rats and male Balb-C mice were used in this study. Giotto Biotech® synthesized the recombinant version of Phα1ß using Escherichia coli expression. In rats, neuropathic pain was induced by chronic constriction of the sciatic nerve and paclitaxel-induced acute and chronic pain. Mechanical sensitivity was evaluated using von Frey filaments. A radiotelemeter transmitter (TA11PA-C10; Data Sciences, St. Paul, MN, USA) was placed on the left carotid of mice for investigation of cardiovascular side effects. Locomotor activity data were evaluated using the open-field paradigm, and serum CKMB, TGO, TGP, LDH, lactate, creatinine, and urea levels were examined. Results: Intravenous administration of recombinant Phα1ß toxin induced analgesia for up to 4 h, with ED50 of 0.02 (0.01-0.03) mg/kg, and reached the maximal effect (Emax = 100% antinociception) at a dose of 0.2 mg/kg. No significant changes were observed in any of the evaluated motor, cardiac or biochemical parameters. Conclusion: Our data suggest that intravenous administration of recombinant Phα1ß may be feasible for drug-induced analgesia, without causing any severe side effects.(AU)

Analgesic and side effects of intravenous recombinant Ph alfa 1 beta

Background: Intrathecal injection of voltage-sensitive calcium channel blocker peptide toxins exerts analgesic effect in several animal models of pain. Upon intrathecal administration, recombinant Phα1β exerts the same analgesic effects as the those of the native toxin. However, from a clinical perspective, the intrathecal administration limits the use of anesthetic drugs in patients. Therefore, this study aimed to investigate the possible antinociceptive effect of intravenous recombinant Phα1β in rat models of neuropathic pain, as well as its side effects on motor, cardiac (heart rate and blood pressure), and biochemical parameters. Methods: Male Wistar rats and male Balb-C mice were used in this study. Giotto Biotech® synthesized the recombinant version of Phα1β using Escherichia coli expression. In rats, neuropathic pain was induced by chronic constriction of the sciatic nerve and paclitaxel-induced acute and chronic pain. Mechanical sensitivity was evaluated using von Frey filaments. A radiotelemeter transmitter (TA11PA-C10; Data Sciences, St. Paul, MN, USA) was placed on the left carotid of mice for investigation of cardiovascular side effects. Locomotor activity data were evaluated using the open-field paradigm, and serum CKMB, TGO, TGP, LDH, lactate, creatinine, and urea levels were examined. Results: Intravenous administration of recombinant Phα1β toxin induced analgesia for up to 4 h, with ED50 of 0.02 (0.01-0.03) mg/kg, and reached the maximal effect (Emax = 100% antinociception) at a dose of 0.2 mg/kg. No significant changes were observed in any of the evaluated motor, cardiac or biochemical parameters. Conclusion: Our data suggest that intravenous administration of recombinant Phα1β may be feasible for drug-induced analgesia, without causing any severe side effects.(AU)

Analgesic and side effects of intravenous recombinant Ph alfa 1 beta

Background: Intrathecal injection of voltage-sensitive calcium channel blocker peptide toxins exerts analgesic effect in several animal models of pain. Upon intrathecal administration, recombinant Phα1β exerts the same analgesic effects as the those of the native toxin. However, from a clinical perspective, the intrathecal administration limits the use of anesthetic drugs in patients. Therefore, this study aimed to investigate the possible antinociceptive effect of intravenous recombinant Phα1β in rat models of neuropathic pain, as well as its side effects on motor, cardiac (heart rate and blood pressure), and biochemical parameters. Methods: Male Wistar rats and male Balb-C mice were used in this study. Giotto Biotech® synthesized the recombinant version of Phα1β using Escherichia coli expression. In rats, neuropathic pain was induced by chronic constriction of the sciatic nerve and paclitaxel-induced acute and chronic pain. Mechanical sensitivity was evaluated using von Frey filaments. A radiotelemeter transmitter (TA11PA-C10; Data Sciences, St. Paul, MN, USA) was placed on the left carotid of mice for investigation of cardiovascular side effects. Locomotor activity data were evaluated using the open-field paradigm, and serum CKMB, TGO, TGP, LDH, lactate, creatinine, and urea levels were examined. Results: Intravenous administration of recombinant Phα1β toxin induced analgesia for up to 4 h, with ED50 of 0.02 (0.01-0.03) mg/kg, and reached the maximal effect (Emax = 100% antinociception) at a dose of 0.2 mg/kg. No significant changes were observed in any of the evaluated motor, cardiac or biochemical parameters. Conclusion: Our data suggest that intravenous administration of recombinant Phα1β may be feasible for drug-induced analgesia, without causing any severe side effects.

Antinociceptive effect of PnTx4(5-5), a peptide from Phoneutria nigriventer spider venom, in rat models and the involvement of glutamatergic system

Background:The venom of Phoneutria nigriventer spider is a source of numerous bioactive substances, including some toxins active in insects. An example is PnTx4(5-5) that shows a high insecticidal activity and no apparent toxicity to mice, although it inhibited NMDA-evoked currents in rat hippocampal neurons. In this work the analgesic activity of PnTx4(5-5) (renamed Γ-ctenitoxin-Pn1a) was investigated.Methods:The antinociceptive activity was evaluated using the paw pressure test in rats, after hyperalgesia induction with intraplantar injection of carrageenan or prostaglandin E2 (PGE2).Results:PnTx4(5-5), subcutaneously injected, was able to reduce the hyperalgesia induced by PGE2 in rat paw, demonstrating a systemic effect. PnTx4(5-5) administered in the plantar surface of the paw caused a peripheral and dose-dependent antinociceptive effect on hyperalgesia induced by carrageenan or PGE2. The hyperalgesic effect observed in these two pain models was completely reversed with 5 µg of PnTx4(5-5). Intraplantar administration of L-glutamate induced hyperalgesic effect that was significantly reverted by 5 μg of PnTx4(5-5) injection in rat paw.Conclusion:The antinociceptive effect for PnTx4(5-5) was demonstrated against different rat pain models, i.e. induced by PGE2, carrageenan or glutamate. We suggest that the antinociceptive effect of PnTx4(5-5) may be related to an inhibitory activity on the glutamatergic system.(AU)

Antinociceptive effect of PnTx4(5-5), a peptide from Phoneutria nigriventer spider venom, in rat models and the involvement of glutamatergic system

The venom of Phoneutria nigriventer spider is a source of numerous bioactive substances, including some toxins active in insects. An example is PnTx4(5-5) that shows a high insecticidal activity and no apparent toxicity to mice, although it inhibited NMDA-evoked currents in rat hippocampal neurons. In this work the analgesic activity of PnTx4(5-5) (renamed Γ-ctenitoxin-Pn1a) was investigated. Methods: The antinociceptive activity was evaluated using the paw pressure test in rats, after hyperalgesia induction with intraplantar injection of carrageenan or prostaglandin E2 (PGE2). Results: PnTx4(5-5), subcutaneously injected, was able to reduce the hyperalgesia induced by PGE2 in rat paw, demonstrating a systemic effect. PnTx4(5-5) administered in the plantar surface of the paw caused a peripheral and dose-dependent antinociceptive effect on hyperalgesia induced by carrageenan or PGE2. The hyperalgesic effect observed in these two pain models was completely reversed with 5 µg of PnTx4(5-5). Intraplantar administration of L-glutamate induced hyperalgesic effect that was significantly reverted by 5 μg of PnTx4(5-5) injection in rat paw. Conclusion: The antinociceptive effect for PnTx4(5-5) was demonstrated against different rat pain models, i.e. induced by PGE2, carrageenan or glutamate. We suggest that the antinociceptive effect of PnTx4(5-5) may be related to an inhibitory activity on the glutamatergic system.(AU)

Antinociceptive activity of Ricinus communis seeds hydroethanolic extract on male Balb/C mice / Atividade antinociceptiva do extrato hidroetanolico de sementes de Ricinus communis em ratos machos

Pain is a normal protective response to tissue injury caused by physical trauma, noxious chemicals and microbiological agents. Use of chemical drugs and medicinal plants is a conventional method to manage pain; however, their side effects have caused increased tendency to the use of herbal medicines among patients. This study was conducted to investigate antinociceptive action of Ricinus communis seeds extract (RCE) in male Balb/C mice. In this experimental study, 72 male mice weighing 25-35gr were used. Animals were randomly divided into six groups of 12 mice each, including: Control group, three groups separately treated respectively with 100, 200, and 400mg/kg hydroethanolic R. communis seed extract, morphine (1mg/kg)-treated group, and naloxone (0.1mg/kg) + R. communis seed extract (200mg/kg)-treated group. All animals received extract and drugs intraperitoneally. To evaluate the analgesic effect of the extract, writhing and tail flick tests were used. The 200 and 400mg/kg of the extract significantly increased pain threshold compared to the control group in writhing and tail flick tests (P<0.01). Moreover, 400mg/kg of the extract showed a stronger antinociceptive effect especially in writhing test compared to the control and other treated groups (P<0.001). Analgesic effects of hydroethanolic R. communis seed extract observed in the tail flick and writhing tests are probably related to activation of opioid system. Results may suggest that this plant extract might be beneficial in relieving human pain.(AU)

A dor é um sentido com efeitos essencialmente protetores. Ouso de drogas químicas e plantas medicinais é um método convencional para gerenciar a dor, no entanto, seus efeitos colaterais têm causado uma maior tendência para o uso de ervas medicamentosas entre os pacientes. Este estudo nos levou a investigar as ações antinociceptivas do extrato de sementes de Ricinus communis (RCE) em camundongos machos. Neste estudo experimental, foram utilizados 72 camundongos machos com peso de 25±30gr. Os animais foram divididos aleatoriamente em seis grupos de 12 cada: grupo controle, três grupos tratados separadamente com 100, 200 e 400mg/kg de extrato de sementes de R. communis hidroetanolico, grupo tratado com morfina (1mg/kg) e naloxona (0,1mg/kg) + R. Grupo tratado com extrato de semente de communis (200mg/kg). Para avaliar o efeito analgésico do extrato, utilizaram-se testes de contorção e cauda. Os dados foram analisados pela ANOVA e pelo teste de Tukey. P<0,05 foi considerado estatisticamente significante. Dose de 200 e 400mg/kg de extrato aumentou significativamente o limite de dor em comparação com o grupo controle em testes de retorção e cauda (P<0,01). Além disso, 400mg/kg de extracto apresentaram efeito antinoceptivo mais forte especialmente no teste de contorção em comparação com o controle e outros grupos tratados (P <0,001). Os efeitos analgésicos do extrato de semente de R. communanolanol foram observados no teste da cauda e nos testes de contorção. Este efeito provavelmente está relacionado à ativação do sistema opioide.(AU)

Avaliação da dexmedetomidina e do tramadol, associados ao midazolam, em gatas anestesiadas com isoflurano e submetidas à ovário-histerectomia

ABSTRACT The aim of this study was to compare cardiorespiratory changes and post-operative analgesia provided by dexmedetomidine or tramadol, associated with midazolam, in female cats. For that purpose, 18 healthy cats were assigned to two randomized groups: GDM, which received dexmedetomidine (10 µg/kg) and GTM, which received tramadol (2 mg/kg), both associated with midazolam (0.2 mg/kg) IM. After 15 minutes, anesthesia was induced with propofol (1.46±0.79 mL) and maintained with isofluorane. Ovariohysterectomy was performed and cardiorespiratory variables were registered 15 minutes after pre-anesthetic medication (M0), 15 minutes after anesthetic induction (M15), and every five minutes until the end of the surgical procedure (M20, M25, M30, M35 e M40). Pain evaluation started 30 minutes after the surgery (MP30) and sequentially at thirty-minute intervals (MP60, MP90, MP120). After MP120, each evaluation was registered at every hour (MP180, MP240 e MP360). Dexmedetomidine-midazolam association results in decreases on initial heart rate (HR) without clinical relevance and it is related to pronounced sedation, poor and less durable antinociception and vomiting events, when compared to tramadol-midazolam association. Both protocols indicate cardiorespiratoy stability and safety in cats undergoing ovariohysterectomy.

RESUMO Objetivou-se comparar as alterações cardiorrespiratórias e a analgesia pós-operatória promovidas pela dexmedetomidina e pelo tramadol, quando associados ao midazolam, em felinas. Para tal, foram selecionadas 18 gatas hígidas, divididas em dois grupos randomizados: GDM, tratadas com dexmedetomidina (10µg/kg) e GTM, tratadas com tramadol (2mg/kg), ambos associados a midazolam (0,2mg/kg,) IM. Após 15 minutos, procedeu-se à indução anestésica com propofol (1,46±0,79mL), mantendo-se a anestesia com isoflurano. As felinas foram submetidas à ovário-histerectomia, registrando-se as variáveis cardiorrespiratórias 15 minutos após a MPA (M0), 15 minutos após a indução (M15) e sequencialmente a cada cinco minutos, até o término do procedimento cirúrgico (M20, M25, M30, M35 e M40). A avaliação da dor iniciou-se 30 minutos após o término do procedimento cirúrgico (MP30) e sequencialmente em intervalos de 30 minutos (MP60, MP90, MP120). A partir do MP120, as avaliações foram registradas a cada hora (MP180, MP240 e MP360). A associação dexmedetomidina-midazolam infere diminuição inicial de frequência cardíaca (FC) sem significado clínico e está relacionada à sedação mais pronunciada, à analgesia menor e menos duradoura e a episódios de êmese, quando comparada à associação tramadol-midazolam. Ambos os protocolos denotaram estabilidade cardiorrespiratória e podem ser considerados seguros em felinas submetidas à ovário-histectomia.

Avaliação da dexmedetomidina e do tramadol, associados ao midazolam, em gatas anestesiadas com isoflurano e submetidas à ovário-histerectomia / Evaluation of dexmedetomidine and tramadol, associated with midazolam, in cats anesthetized with isoflurane, undergoing ovariohysterectomy

Objetivou-se comparar as alterações cardiorrespiratórias e a analgesia pós-operatória promovidas pela dexmedetomidina e pelo tramadol, quando associados ao midazolam, em felinas. Para tal, foram selecionadas 18 gatas hígidas, divididas em dois grupos randomizados: GDM, tratadas com dexmedetomidina (10µg/kg) e GTM, tratadas com tramadol (2mg/kg), ambos associados a midazolam (0,2mg/kg,) IM. Após 15 minutos, procedeu-se à indução anestésica com propofol (1,46±0,79mL), mantendo-se a anestesia com isoflurano. As felinas foram submetidas à ovário-histerectomia, registrando-se as variáveis cardiorrespiratórias 15 minutos após a MPA (M0), 15 minutos após a indução (M15) e sequencialmente a cada cinco minutos, até o término do procedimento cirúrgico (M20, M25, M30, M35 e M40). A avaliação da dor iniciou-se 30 minutos após o término do procedimento cirúrgico (MP30) e sequencialmente em intervalos de 30 minutos (MP60, MP90, MP120). A partir do MP120, as avaliações foram registradas a cada hora (MP180, MP240 e MP360). A associação dexmedetomidina-midazolam infere diminuição inicial de frequência cardíaca (FC) sem significado clínico e está relacionada à sedação mais pronunciada, à analgesia menor e menos duradoura e a episódios de êmese, quando comparada à associação tramadol-midazolam. Ambos os protocolos denotaram estabilidade cardiorrespiratória e podem ser considerados seguros em felinas submetidas à ovário-histectomia.(AU)

The aim of this study was to compare cardiorespiratory changes and post-operative analgesia provided by dexmedetomidine or tramadol, associated with midazolam, in female cats. For that purpose, 18 healthy cats were assigned to two randomized groups: GDM, which received dexmedetomidine (10 µg/kg) and GTM, which received tramadol (2 mg/kg), both associated with midazolam (0.2 mg/kg) IM. After 15 minutes, anesthesia was induced with propofol (1.46±0.79 mL) and maintained with isofluorane. Ovariohysterectomy was performed and cardiorespiratory variables were registered 15 minutes after pre-anesthetic medication (M0), 15 minutes after anesthetic induction (M15), and every five minutes until the end of the surgical procedure (M20, M25, M30, M35 e M40). Pain evaluation started 30 minutes after the surgery (MP30) and sequentially at thirty-minute intervals (MP60, MP90, MP120). After MP120, each evaluation was registered at every hour (MP180, MP240 e MP360). Dexmedetomidine-midazolam association results in decreases on initial heart rate (HR) without clinical relevance and it is related to pronounced sedation, poor and less durable antinociception and vomiting events, when compared to tramadol-midazolam association. Both protocols indicate cardiorespiratoy stability and safety in cats undergoing ovariohysterectomy.(AU)

Avaliação da dexmedetomidina e do tramadol, associados ao midazolam, em gatas anestesiadas com isoflurano e submetidas à ovário-histerectomia / Evaluation of dexmedetomidine and tramadol, associated with midazolam, in cats anesthetized with isoflurane, undergoing ovariohysterectomy

Objetivou-se comparar as alterações cardiorrespiratórias e a analgesia pós-operatória promovidas pela dexmedetomidina e pelo tramadol, quando associados ao midazolam, em felinas. Para tal, foram selecionadas 18 gatas hígidas, divididas em dois grupos randomizados: GDM, tratadas com dexmedetomidina (10µg/kg) e GTM, tratadas com tramadol (2mg/kg), ambos associados a midazolam (0,2mg/kg,) IM. Após 15 minutos, procedeu-se à indução anestésica com propofol (1,46±0,79mL), mantendo-se a anestesia com isoflurano. As felinas foram submetidas à ovário-histerectomia, registrando-se as variáveis cardiorrespiratórias 15 minutos após a MPA (M0), 15 minutos após a indução (M15) e sequencialmente a cada cinco minutos, até o término do procedimento cirúrgico (M20, M25, M30, M35 e M40). A avaliação da dor iniciou-se 30 minutos após o término do procedimento cirúrgico (MP30) e sequencialmente em intervalos de 30 minutos (MP60, MP90, MP120). A partir do MP120, as avaliações foram registradas a cada hora (MP180, MP240 e MP360). A associação dexmedetomidina-midazolam infere diminuição inicial de frequência cardíaca (FC) sem significado clínico e está relacionada à sedação mais pronunciada, à analgesia menor e menos duradoura e a episódios de êmese, quando comparada à associação tramadol-midazolam. Ambos os protocolos denotaram estabilidade cardiorrespiratória e podem ser considerados seguros em felinas submetidas à ovário-histectomia.(AU)

The aim of this study was to compare cardiorespiratory changes and post-operative analgesia provided by dexmedetomidine or tramadol, associated with midazolam, in female cats. For that purpose, 18 healthy cats were assigned to two randomized groups: GDM, which received dexmedetomidine (10 µg/kg) and GTM, which received tramadol (2 mg/kg), both associated with midazolam (0.2 mg/kg) IM. After 15 minutes, anesthesia was induced with propofol (1.46±0.79 mL) and maintained with isofluorane. Ovariohysterectomy was performed and cardiorespiratory variables were registered 15 minutes after pre-anesthetic medication (M0), 15 minutes after anesthetic induction (M15), and every five minutes until the end of the surgical procedure (M20, M25, M30, M35 e M40). Pain evaluation started 30 minutes after the surgery (MP30) and sequentially at thirty-minute intervals (MP60, MP90, MP120). After MP120, each evaluation was registered at every hour (MP180, MP240 e MP360). Dexmedetomidine-midazolam association results in decreases on initial heart rate (HR) without clinical relevance and it is related to pronounced sedation, poor and less durable antinociception and vomiting events, when compared to tramadol-midazolam association. Both protocols indicate cardiorespiratoy stability and safety in cats undergoing ovariohysterectomy.(AU)

A spider derived peptide, PnPP-19, induces central antinociception mediated by opioid and cannabinoid systems

Background: Some peptides purified from the venom of the spider Phoneutria nigriventer have been identified as potential sources of drugs for pain treatment. In this study, we characterized the antinociceptive effect of the peptide PnPP-19 on the central nervous system and investigated the possible involvement of opioid and cannabinoid systems in its action mechanism. Methods: Nociceptive threshold to thermal stimulation was measured according to the tail-flick test in Swiss mice. All drugs were administered by the intracerebroventricular route.Results: PnPP-19 induced central antinociception in mice in the doses of 0.5 and 1 µg. The non-selective opioid receptor antagonist naloxone (2.5 and 5 µg), µ-opioid receptor antagonist clocinnamox (2 and 4 µg), δ-opioid receptor antagonist naltrindole (6 and 12 µg) and CB1 receptor antagonist AM251 (2 and 4 µg) partially inhibited the antinociceptive effect of PnPP-19 (1 µg). Additionally, the anandamide amidase inhibitor MAFP (0.2 µg), the anandamide uptake inhibitor VDM11 (4 µg) and the aminopeptidase inhibitor bestatin (20 µg) significantly enhanced the antinociception induced by a low dose of PnPP-19 (0.5 µg). In contrast, the κ-opioid receptor antagonist nor-binaltorphimine (10 µg and 20 µg) and the CB2 receptor antagonist AM630 (2 and 4 µg) do not appear to be involved in this effect. Conclusions: PnPP-19-induced central antinociception involves the activation of CB1 cannabinoid, µ- and δ-opioid receptors. Mobilization of endogenous opioids and cannabinoids might be required for the activation of those receptors, since inhibitors of endogenous substances potentiate the effect of PnPP-19. Our results contribute to elucidating the action of the peptide PnPP-19 in the antinociceptive pathway.(AU)

A spider derived peptide, PnPP-19, induces central antinociception mediated by opioid and cannabinoid systems

Some peptides purified from the venom of the spider Phoneutria nigriventer have been identified as potential sources of drugs for pain treatment. In this study, we characterized the antinociceptive effect of the peptide PnPP-19 on the central nervous system and investigated the possible involvement of opioid and cannabinoid systems in its action mechanism. Methods Nociceptive threshold to thermal stimulation was measured according to the tail-flick test in Swiss mice. All drugs were administered by the intracerebroventricular route. Results PnPP-19 induced central antinociception in mice in the doses of 0.5 and 1 g. The non-selective opioid receptor antagonist naloxone (2.5 and 5 g), -opioid receptor antagonist clocinnamox (2 and 4 g), -opioid receptor antagonist naltrindole (6 and 12 g) and CB1 receptor antagonist AM251 (2 and 4 g) partially inhibited the antinociceptive effect of PnPP-19 (1 g). Additionally, the anandamide amidase inhibitor MAFP (0.2 g), the anandamide uptake inhibitor VDM11 (4 g) and the aminopeptidase inhibitor bestatin (20 g) significantly enhanced the antinociception induced by a low dose of PnPP-19 (0.5 g). In contrast, the -opioid receptor antagonist nor-binaltorphimine (10 g and 20 g) and the CB2 receptor antagonist AM630 (2 and 4 g) do not appear to be involved in this effect. Conclusions PnPP-19-induced central antinociception involves the activation of CB1 cannabinoid, - and -opioid receptors. Mobilization of endogenous opioids and cannabinoids might be required for the activation of those receptors, since inhibitors of endogenous substances potentiate the effect of PnPP-19. Our results contribute to elucidating the action of the peptide PnPP-19 in the antinociceptive pathway.(AU)

A spider derived peptide, PnPP-19, induces central antinociception mediated by opioid and cannabinoid systems

Some peptides purified from the venom of the spider Phoneutria nigriventer have been identified as potential sources of drugs for pain treatment. In this study, we characterized the antinociceptive effect of the peptide PnPP-19 on the central nervous system and investigated the possible involvement of opioid and cannabinoid systems in its action mechanism. Methods Nociceptive threshold to thermal stimulation was measured according to the tail-flick test in Swiss mice. All drugs were administered by the intracerebroventricular route. Results PnPP-19 induced central antinociception in mice in the doses of 0.5 and 1 g. The non-selective opioid receptor antagonist naloxone (2.5 and 5 g), -opioid receptor antagonist clocinnamox (2 and 4 g), -opioid receptor antagonist naltrindole (6 and 12 g) and CB1 receptor antagonist AM251 (2 and 4 g) partially inhibited the antinociceptive effect of PnPP-19 (1 g). Additionally, the anandamide amidase inhibitor MAFP (0.2 g), the anandamide uptake inhibitor VDM11 (4 g) and the aminopeptidase inhibitor bestatin (20 g) significantly enhanced the antinociception induced by a low dose of PnPP-19 (0.5 g). In contrast, the -opioid receptor antagonist nor-binaltorphimine (10 g and 20 g) and the CB2 receptor antagonist AM630 (2 and 4 g) do not appear to be involved in this effect. Conclusions PnPP-19-induced central antinociception involves the activation of CB1 cannabinoid, - and -opioid receptors. Mobilization of endogenous opioids and cannabinoids might be required for the activation of those receptors, since inhibitors of endogenous substances potentiate the effect of PnPP-19. Our results contribute to elucidating the action of the peptide PnPP-19 in the antinociceptive pathway.

Evaluation of the cardiopulmonary and antinociceptive effects of bupivacaine administered epidurally at the first lumbar vertebra in awake dogs / Estudo dos efeitos cardiopulmonares e antinociceptivos da administração epidural de bupivacaína à altura da primeira vértebra lombar em cães acordados

The aim of this study was to evaluate the effect of epidural bupivacaine administration at the first lumbar vertebra on cardiopulmonary variables, arterial blood gases and anti-nociception. Sixteen healthy female dogs were randomly assigned into two groups based on bupivacaine dose: G1 group, 1mg kg-1 or G2 group, 2mg kg-1, diluted in the same final volume (1mL4kg-1). Cardiopulmonary variables were measured and arterial blood gas was collected (T0), it was repeated 10 minutes after intravenous administration of butorphanol 0.4mg kg -1 (T1). Anesthesia was induced with intravenous etomidate at 2mg kg-1 and the epidural catheter was introduced and placed at the first lumbar vertebra. Thirty minutes later, bupivacaine was administered epidurally. Cardiopulmonary measurements and arterial blood gas analysis were recorded at 10 minute intervals (T2 to T6). Evaluation of pre surgical anti-nociception was performed at 5 minute intervals for 30 minutes by clamping the hind limbs, anus, vulva, and tail with the dogs awake. Subsequently, ovariohysterectomy was performed and adequacy of surgical anti-nociception was evaluated at 5 time points. Parametric data were analyzed using the F test with a <0.05 significance. After bupivacaine administration, there were differences between groups just for bicarbonate means (HCO3-) on T6 (P=0.0198), with 18.7±1.3 and 20.4±0.8 for G1 and G2, respectively. After T1, before bupivacaine administration, both groups presented a slightly lower pH, base excess (BE), the end-tidal carbon dioxide tension (PECO2), and partial pressure of carbon dioxide (PaCO2), suggesting mild metabolic acidosis. G2 showed better antinociceptive effect both before and during surgery. It was possible to perform ovariohysterectomy in 87.5% of the G2 bitches and 25% of the G1 bitches. The two doses of bupivacaine evaluated do not cause important alterations in the studied parameters and the dose of 2mg kg-1 results in a better antinociceptive effect.(AU)

O objetivo deste estudo foi avaliar os efeitos da administração epidural de bupivacaína à altura da primeira vértebra lombar sobre variáveis cardiopulmonares, hemogasometria arterial e antinocicepção. Dezesseis cadelas foram separadas aleatoriamente em dois grupos que se diferenciaram pela dose de bupivacaína, 1mg/kg (G1) ou 2mg/kg (G2), diluídas no mesmo volume final (1mL/4kg). As variáveis cardiopulmonares e hemogasometria arterial foram coletadas antes (T0) e após 10 minutos da administração intravenosa de 0,4mg/kg de butorfanol (T1). A anestesia foi induzida com 2mg/kg de etomidato intravenoso para introdução do cateter epidural. Após 30 minutos, a bupivacaína foi administrada e, passados 10 minutos, nova coleta de parâmetros foi feita, sendo repetida a cada 10 minutos (T2 a T6). Após cinco minutos da administração de bupivacaína, iniciou-se a avaliação da antinocicepção pré-cirúrgica, repetida a cada cinco minutos durante 30 minutos. Então, iniciou-se a cirurgia de ovário-histerectomia, na qual se avaliou a antinocicepção transcirúrgica em cinco momentos. Os resultados paramétricos foram analisados pelo software SAS 9.4 (2010), utilizando-se o teste F com significância menor que 0,05. Houve diferença entre as médias dos grupos após administração de bupivacaína apenas para bicarbonato em T6 (P=0.0198), sendo 18,7±1,3 e 20,4±0,8 as médias do G1 e G2, respectivamente. Desde T1, os grupos apresentaram valores de pH, excesso de bases, pressão parcial de gás carbônico no sangue arterial e tensão de dióxido de carbono ao final da expiração pouco abaixo do fisiológico, sugerindo acidose metabólica discreta. O G2 apresentou efeito antinociceptivo pré e transcirúrgico superior ao G1. [...](AU)

Evaluation of the cardiopulmonary and antinociceptive effects of bupivacaine administered epidurally at the first lumbar vertebra in awake dogs / Estudo dos efeitos cardiopulmonares e antinociceptivos da administração epidural de bupivacaína à altura da primeira vértebra lombar em cães acordados

The aim of this study was to evaluate the effect of epidural bupivacaine administration at the first lumbar vertebra on cardiopulmonary variables, arterial blood gases and anti-nociception. Sixteen healthy female dogs were randomly assigned into two groups based on bupivacaine dose: G1 group, 1mg kg-1 or G2 group, 2mg kg-1, diluted in the same final volume (1mL4kg-1). Cardiopulmonary variables were measured and arterial blood gas was collected (T0), it was repeated 10 minutes after intravenous administration of butorphanol 0.4mg kg -1 (T1). Anesthesia was induced with intravenous etomidate at 2mg kg-1 and the epidural catheter was introduced and placed at the first lumbar vertebra. Thirty minutes later, bupivacaine was administered epidurally. Cardiopulmonary measurements and arterial blood gas analysis were recorded at 10 minute intervals (T2 to T6). Evaluation of pre surgical anti-nociception was performed at 5 minute intervals for 30 minutes by clamping the hind limbs, anus, vulva, and tail with the dogs awake. Subsequently, ovariohysterectomy was performed and adequacy of surgical anti-nociception was evaluated at 5 time points. Parametric data were analyzed using the F test with a <0.05 significance. After bupivacaine administration, there were differences between groups just for bicarbonate means (HCO3-) on T6 (P=0.0198), with 18.7±1.3 and 20.4±0.8 for G1 and G2, respectively. After T1, before bupivacaine administration, both groups presented a slightly lower pH, base excess (BE), the end-tidal carbon dioxide tension (PECO2), and partial pressure of carbon dioxide (PaCO2), suggesting mild metabolic acidosis. G2 showed better antinociceptive effect both before and during surgery. It was possible to perform ovariohysterectomy in 87.5% of the G2 bitches and 25% of the G1 bitches. The two doses of bupivacaine evaluated do not cause important alterations in the studied parameters and the dose of 2mg kg-1 results in a better antinociceptive effect.(AU)

O objetivo deste estudo foi avaliar os efeitos da administração epidural de bupivacaína à altura da primeira vértebra lombar sobre variáveis cardiopulmonares, hemogasometria arterial e antinocicepção. Dezesseis cadelas foram separadas aleatoriamente em dois grupos que se diferenciaram pela dose de bupivacaína, 1mg/kg (G1) ou 2mg/kg (G2), diluídas no mesmo volume final (1mL/4kg). As variáveis cardiopulmonares e hemogasometria arterial foram coletadas antes (T0) e após 10 minutos da administração intravenosa de 0,4mg/kg de butorfanol (T1). A anestesia foi induzida com 2mg/kg de etomidato intravenoso para introdução do cateter epidural. Após 30 minutos, a bupivacaína foi administrada e, passados 10 minutos, nova coleta de parâmetros foi feita, sendo repetida a cada 10 minutos (T2 a T6). Após cinco minutos da administração de bupivacaína, iniciou-se a avaliação da antinocicepção pré-cirúrgica, repetida a cada cinco minutos durante 30 minutos. Então, iniciou-se a cirurgia de ovário-histerectomia, na qual se avaliou a antinocicepção transcirúrgica em cinco momentos. Os resultados paramétricos foram analisados pelo software SAS 9.4 (2010), utilizando-se o teste F com significância menor que 0,05. Houve diferença entre as médias dos grupos após administração de bupivacaína apenas para bicarbonato em T6 (P=0.0198), sendo 18,7±1,3 e 20,4±0,8 as médias do G1 e G2, respectivamente. Desde T1, os grupos apresentaram valores de pH, excesso de bases, pressão parcial de gás carbônico no sangue arterial e tensão de dióxido de carbono ao final da expiração pouco abaixo do fisiológico, sugerindo acidose metabólica discreta. O G2 apresentou efeito antinociceptivo pré e transcirúrgico superior ao G1. Foi possível realizar a cirurgia em 87,5% das cadelas do G2 e em 25% das cadelas do G1. Concluiu-se que as duas doses de bupivacaína avaliadas não acarretam alterações importantes nos parâmetros fisiológicos estudados e a dose de 2mg/kg determina melhor efeito antinociceptivo que a dose de 1mg/kg.(AU)

Protective effects of ethanolic extract from the red algae Amansia multifida on experimental inflammation, nociception and seizure experimental models / Efeito protetor do extrato etanólico da alga marinha vermelha Amansia multifida em modelos experimentais de inflamação, nocicepção e convulsão

This study aimed to investigate the EEAm effect in mice models of nociception, inflammation and in behavioral tests evaluating the central nervous system. EEAm had inhibitory effects in the following tests: acetic acid-induced writhing (78%); formalin (62% - inflammatory phase); open field (46%). EEAm increased the nociceptive latency (56%) in tail flick test and increased the death-latency by 36% in the pentylenetetrazole-induced seizure model. Moreover, EEAm inhibited paw edema (82%) and peritonitis (45%) induced by carrageenan. In conclusion, EEAm presents antinociceptive, antiinflammatory and anticonvulsant effects involving peripheral and central-acting mechanisms in mice.(AU)

Neste estudo objetivou-se investigar o efeito do EEAm em modelos de nocicepção e inflamação, e em testes comportamentais que avaliam o sistema nervoso central em camundongos. EEAm exibiu efeitos inibitórios nos testes comportamentais de contorções abdominais induzidas por ácido acético (78%); formalina (62% - fase inflamatória) e campo aberto (46%). EEAm aumentou a latência de nocicepção no teste de retirada da cauda (56%) e a latência de morte 36% no modelo de convulsões induzidas por pentilenetetrazol. Além disso, EEAm inibiu o edema de pata (82%) e a peritonite (45%) induzidos por carragenana. Como conclusão, EEAm apresenta efeitos antinociceptivo, anti-inflamatório e anticonvulsivante em camundongos por mecanismos periféricos e centrais.(AU)

Efeitos da morfina e metadona sobre o comportamento e crescimento tumoral de camundongos com tumor de Ehrlich

RUSCH, E. Efeitos da morfina e metadona sobre o comportamento e crescimento tumoral de camundongos com tumor de Ehrlich. 2020. Dissertação (Mestrado). Faculdade de Zootecnia e Engenharia de Alimentos, Universidade de São Paulo, Pirassununga, 2020. A morfina e a metadona, embora sejam fármacos recomendados para promover analgesia, parecem promover alterações comportamentais e influenciar no crescimento tumoral em modelos experimentais. Diante disso, o objetivo do estudo consistiu em avaliar os efeitos da morfina e metadona sobre o comportamento, antinocicepção e crescimento tumoral em camundongos. O estudo foi dividido em duas partes. No primeiro experimento foram utilizados 53 camundongos, fêmeas, com 60 ± 10 dias de idade que foram inoculados com tumor ascítico de Ehrlich (TAE) por via intraperitoneal. Após sete dias da inoculação, os animais foram distribuídos aleatoriamente em 7 grupos, morfina 5 mg/kg (Morf5), morfina 7,5 mg/kg (Morf7,5), morfina 10 mg/kg (Morf10), metadona 2,85 mg/kg (Met2,85), metadona 4,3 mg/kg (Met4,3), metadona 5,7 mg/kg (Met5,7) e solução salina NaCl 0,9% (Salina). Os tratamentos foram administrados por via subcutânea, a cada seis horas, durante três dias. Os animais foram avaliados quanto a atividade geral em campo aberto e nocicepção, por meio do teste de pinçamento de cauda, os quais foram realizados antes da inoculação tumoral (dia 0), aos 40, 90, 150, 240 e 360 minutos após o início dos tratamentos (dia 7) e 40, 150 e 360 minutos após os dias 8 e 9 pós-inoculação. Todas as doses promoveram aumento significativo da distância percorrida e velocidade média de maneira dose-dependente, sendo que os efeitos foram mais pronunciados nos dias 8 e 9. As frequências de levantar e de autolimpeza reduziram de maneira significativa após a administração de morfina e metadona em todas as doses até os 90 minutos. O segundo experimento consistiu em avaliar os efeitos sobre o crescimento tumoral das mesmas doses da morfina e metadona administradas por via subcutânea, a cada 6 horas, durante 8 dias, iniciados 24 horas após a inoculação tumoral. Os animais foram avaliados diariamente quanto ao peso e circunferência abdominal e nove dias após a inoculação tumoral, foram submetidos à eutanásia. O líquido ascítico foi colhido para aferição do volume, verificação da característica do líquido, contagem de células tumorais e análise do ciclo celular. Todos os animais apresentaram aumento de peso e de circunferência abdominal ao longo dos dias. O volume do líquido ascítico peritoneal foi menor nos tratamentos Morf5, Morf10 e em todas as doses testadas de metadona em comparação ao grupo Salina. A viabilidade e o número de células totais não diferiram entre os tratamentos. Os tratamentos Morf10 e Met5,7 interferiram no ciclo celular das células tumorais com maior porcentagem de células na fase G1 do ciclo, em comparação ao grupo Salina. Observou-se, a partir do primeiro experimento que todas as doses testadas promovem aumento da locomoção e redução de comportamentos exploratórios que foram mais evidentes ao longo dos dias de tratamento. A antinocicepção é observada por até 40 minutos em dose única e prolonga-se por até 150 minutos após administrações seriadas nas doses intermediárias e maiores. Os tratamentos Morf10 e Met5,7 promovem estase do ciclo celular, mas não interferem de maneira significativa no crescimento do tumor ascítico de Ehrlich.

RUSCH, E. Effects of morphine and methadone on the behavior and tumor growth of mice with Ehrlich tumor. 2020. 26 f. M.Sc. Dissertation - Faculdade de Zootecnia e Engenharia de Alimentos, University of Sao Paulo, Pirassununga, 2020. The objective of this research is to evaluate the effects of morphine and methadone on behavior, antinociception and tumor growth in mice. The study was dived into two parts. In the first experiment, Fifty-three female mice, 60 ± 10 days old, were inoculated with Ehrlich's ascitic tumor (EAT) intraperitoneally. Seven days after intraperitoneal tumour inoculation (2 × 106 cells), the animals were randomised into seven groups: morphine 5 mg/kg (MO5), morphine 7.5 mg/kg (MO7.5), morphine 10 mg/kg (MO10), methadone 2.85 mg/kg (ME2.85), methadone 4.3 mg/kg (ME4.3), methadone 5.7 mg/kg (ME5.7), and 0.9% NaCl (Sal). Treatments were administered subcutaneously, every 6 h, for 3 days. The animals were evaluated for general activity and nociception using the open field and tail clip tests, respectively. These tests were performed before tumour inoculation (day 0); at 40, 90, 150, 240, and 360 min following treatment initiation (day 7); and at 40, 150, and 360 min after days 8 and 9 post-inoculation. All evaluated doses promoted a significant dose-dependent increase in the total distance travelled and the average speed, markedly pronounced on days 8 and 9 than on day 7. The frequencies of rearing and self-grooming decreased significantly after morphine or methadone administration. The second experiment consisted of evaluating the effects on tumor growth of the same doses of morphine and methadone administered subcutaneously, every 6 hours, for 8 days, starting 24 hours after tumor inoculation. The animals were evaluated daily for weight and abdominal circumference and they were euthanized nine days after the tumor inoculation. The ascitic fluid was collected to measure the volume, check the characteristic of the liquid, count the tumor cells and analyze the cell cycle. All animals had increased weight and waist circumference over the days. The volume of peritoneal ascitic fluid was lower in the Morf5, Morf10 treatments and in all tested methadone doses compared to the Saline group. Viability and number of total cells did not differ between treatments. Morf10 and Met5,7 treatments interfered in the cell cycle of tumor cells, with a higher percentage of cells in the G1 phase of the cycle, compared to the Saline group. It was observed, from the first experiment, that all doses tested promote increased locomotion and reduced exploratory behaviors that were more evident over the treatment days. Antinociception was observed for up to 40 minutes in a single dose and continued for up to 150 minutes after serial administrations in intermediate and higher doses. The Morf10 and Met5,7 treatments promoted cell cycle stasis, but did not significantly interfere with the growth of Ehrlich's ascites tumor.

AVALIAÇÃO DA SEDAÇÃO, DAS ALTERAÇÕES ELETROCARDIOGRÁFICAS E DA DOPPLERVELOCIMETRIA RENAL UTILIZANDO DETOMIDINA, MEDETOMIDINA E DEXMEDETOMIDINA ASSOCIADO A S-CETAMINA EM FELINOS DOMÉSTICOS

Felinos são animais suscetíveis a desenvolver patologias renais e muitos não permitem manipulação sem sedação e esse é um ponto chave para o veterinário anestesista, sendo assim deve-se estabelecer protocolos seguros e que sejam eficientes, sem causar grandes alterações no organismo dos felinos, já que alterações hemodinâmicas muito intensas podem desencadear lesão renal aguda. Esse trabalho avaliou três protocolos com s-cetamina (5 mg/kg) associada à dexmedetomidina 7 µg/kg (GDEX), medetomidina 25 µg/kg (GMEDETO) e detomidina 60 µg/kg (GDETO) IM ,quanto aos seus efeitos sedativos, antinociceptivos, hemodinâmicos, eletrocardiográficos e dopplervelocimétricos renais, além de análises de UPC e GGT urinária para identificação de lesão renal aguda. O tempo de latência dos grupos variou entre 4 e 5 minutos, sendo que 1 animal do GMEDETO demorou 13 minutos. Não foi observado diferença estatística quanto a antinocicepção com o método de avaliação von Frey, porém o GDEX se mostrou superior quanto ao piçamento de pele em comparação ao GDETO. Os grupos não apresentaram diferença quanto ao período de sedação, ambos ficaram em torno de 1h sedados, e após 4h estavam completamente recuperados. As alterações eletrocardiográficas encontradas foram arritmia sinusal, BAV e parada sinusal, e ainda o GMEDETO apresentou VPC até 30 minutos após sedação, não sendo relacionado à alterações hidroeletrolíticas. Todos apresentaram bradicardia, bradpneia e aumento de PAS. Um animal do GDEX apresentou intensa taquicardia e hipotensão no M2h. Pela ação dos alfa dois adrenérgico no pâncreas todos os animais apresentaram hiperglicemia. Os animais apresentavam-se com hiperlactatemia e após sedação os valores se normalizaram (abaixo de 3,2 mmol/l). Com relação a detecção de lesão renal aguda, podemos concluir que nas primeiras 24h após a sedação não houveram índicios de lesão, porém os animais do GDETO apresentaram valores crescentes de UPC até 24h após a sedação, terminando as análises como proteinúricos.

Felines are animals susceptible to develop renal pathologies and many do not allow manipulation without sedation and this is a key point for the anesthetist veterinarian, so it is necessary to establish safe and efficient protocols without causing great changes in the body of the felines, since very hemodynamic changes can trigger acute renal injury. This study evaluated three protocols with s-ketamine (5 mg / kg) associated with dexmedetomidine 7 g / kg (GDEX), medetomidine 25 g / kg (GMEDETO) and detomidine 60 g / kg (GDETO) IM, as to its sedative effects , antinociceptive, hemodynamic, electrocardiographic and renal Doppler velocimetric tests, as well as UPC and urinary GGT analyzes to identify acute renal injury. The latency time of the groups varied between 4 and 5 minutes, and 1 animal of the GMEDET took 13 minutes. No statistical difference was observed for antinociception with the von Frey method, but the GDEX was superior in relation to the skin pinching in comparison to the GDETO. The groups did not present any difference regarding the sedation period, both were sedated for 1h, and after 4h they were fully recovered. The electrocardiographic alterations were sinusal arrhythmia, AVB and sinus arrest, and the GMEDETO presented VPC up to 30 minutes after sedation, and was not related to hydroelectrolytic alterations. All presented bradycardia, bradypnoea and increased SBP. A GDEX animal presented intense tachycardia and hypotension in M2h. By the action of alpha 2 adrenergic in the pancreas all the animals presented hyperglycemia. The animals presented with hyperlactatemia and after sedation the values normalized (below 3.2 mmol / l). Regarding the detection of acute renal injury, we can conclude that in the first 24 hours after sedation there were no indications of injury, but the animals of the GDETO showed increasing values of UPC up to 24h after sedation, ending the analyzes as proteinuric