Maropitant is a neurokinin-1 (NK1) receptor antagonist that can be used for pain management. The objective of this study was to evaluate the effect of continuous infusion of two doses of maropitant on cardiorespiratory parameters and its postoperative analgesic effect in cats undergoing ovariohysterectomy. Thirty cats were randomly assigned to one of three groups (10 cats each group): the control group (CG) received a continuous infusion of 10 ml/kg/h Ringer’s lactate; GM30 and GM100 first received an intravenous (IV) bolus of 1 mg/kg maropitant; GM30 then received continuous infusion of 30 μg/kg/h maropitant; and GM100 then received continuous infusion of 100 μg/kg/h maropitant. The maropitant was diluted into Ringer’s lactate and the GM30 and GM100 also received fluids intraoperatively. In all groups, premedication included intramuscular injections of morphine and acepromazine, followed by induction with propofol and maintenance with isoflurane. Temperature, heart rate (HR), Doppler blood pressure (DBP), respiratory rate, oxygen saturation, and measuring the end-tidal carbon dioxide and isoflurane were monitored. Postoperative pain was evaluated using a visual analog scale and the UNESP-Botucatu multidimensional composite pain scale in cats; morphine was used for analgesic rescue. During the surgical procedure, cats in GM100 demonstrated lower HR and DBP than those in CG. With regard to the evaluation of postoperative pain, GM100 required the least frequent morphine rescue and less rescue analgesia compared with CG. In conclusion, cats in GM100 maintained lower DBP and HR and required lower analgesic rescue during the postoperative period. The results suggested that animals receiving maropitant bolus (1 mg/kg) plus (100 μg/kg/h) experienced greater postoperative comfort, reflected by the lesser need for analgesic rescue. The use of maropitant in surgical procedures in cats contributes to postoperative comfort.

Maropitant, an antagonist of neurokinin-1 (NK-1) receptors, blocks the pharmacological action of substance P on the central and peripheral nervous systems. The objective of this study was to compare the antinociceptive and cardiorespiratory effects of the continuous intraoperative infusion of maropitant with ketamine and lidocaine in female dogs undergoing unilateral radical mastectomy. Twenty-four female dogs were used and were divided randomly into two groups (n = 12). The GLK group received ketamine bolus (1.0 mg/kg), lidocaine bolus (1.5 mg/kg), and continuous infusion of ketamine and lidocaine (10 mcg/kg/min and 50 mcg/kg/min), respectively; the GLKM group received the same anesthetic protocol combined with maropitant bolus (1.5 mg/kg/IV) and continuous infusion of maropitant (100 mcg/kg/h). Continuous infusion was initiated at the start of surgery and was maintained until 1 hour postoperatively. Pain was evaluated in the postoperative period using four scales and a digital analgesimeter. Data were analysed using analysis of variance, Student's t-test, Mann–Whitney test, and Friedman’s test ( < 0.05). Kaplan–Meier curves were compared using the log-rank test. The results indicated lower pain scores, better survival curves with a lower number of patients requiring rescue analgesia, and lower peripheral sensitization, in the GLKM group than in the GLK group. It was concluded that the coadministration of maropitant with ketamine and lidocaine had an adjuvant effect with minimal cardiorespiratory effects and effective analgesia, improving pain management and patient comfort.

Background: Multimodal analgesia consists of the combination of analgesic drugs at low doses to act in different places along the path of pain. Studies with continuous infusion of analgesic drugs in cats are not common. This study aimed to evaluate the analgesic effect of maropitant, lidocaine and ketamine alone or in combination (intravenous bolus + subsequent continuous intravenous infusion) in the management of acute postoperative pain in cats undergoing ovariohysterectomy. Seventy healthy cats undergoing an ovariohysterectomy received a standard anesthetic protocol consisting of acepromazine and morphine, propofol (anesthesia induction), and isoflurane (anesthesia maintenance). The animals were stratified into seven groups (n = 10 in each group): control (CG), maropitant (MG), lidocaine (LG), ketamine (KG), maropitant + lidocaine (LMG), maropitant + ketamine (KMG), and maropitant + lidocaine + ketamine (LKMG). All drugs were injected first as an intravenous bolus and then by continuous intravenous infusion. During surgery, esophageal temperature, respiratory rate, heart rate, oxygen saturation, expired isoflurane concentration, and partial pressure of carbon dioxide at the end of expiration were evaluated at 7 time points. Postoperative pain was evaluated for 6 h after extubation using the visual analogue scale and the UNESP-Botucatu multidimensional composite pain scale for assessing postoperative pain in cats.Results: Adverse effects related to maropitant, lidocaine and ketamine infusion were not observed. Pain scores were lower in the MG, KG and LG groups when compared to the CG group using both scales. Although pain scores were also lower in all combination groups than CG, more animals in these groups required rescue analgesia compared to MG. This indicates that the postoperative analgesic effect of all drugs, either alone or in combination, confers analgesia, although the combinations did not promote greater analgesia.Conclusions: Continuous intravenous infusion of maropitant, lidocaine, and ketamine alone induces postoperative analgesic effect in cats undergoing ovariohysterectomy, but combinations of these drugs did not increase the analgesic effect. No adverse effect was observed with any drug or their combination.

Objective: To determine the effective dose and therapeutic potential of maropitant using through expression of mediators of oxidative stress, inflammatory and of the unfolded protein response (UPR) (bio) markers on spinal cord using a model of neuropathic pain induced through chronic constriction injury (CCI) in rats. Study design: Randomized, blinded, prospective experimental study. Animals: 98 male Wistar rats. Methods: Rats were anesthetized with sevoflurane and after CCI, they were randomly assigned to the following groups that received: vehicle, 3, 6, 15, 30 e 50 mg/kg/24q of maropitant. The effect on inflammatory mediators (IL_10, TNFα), oxidative stress (GPx, CAT, SOD), microglial (IBA-1) and neuronal (NeuN, TACR1) markers was evaluated though immunohistochemistry and expression levels of markers of hypoxia (HIF1α, Nrf2), antioxidant enzymes (Catalse, Sod1 and GPx1), and endoplasmic reticulum stress mediators (GRP78, CHOP and PERK) through qRT-PCR. Results: Intraperitoneal injection (IP) of maropitant inhibited nociception with ID₅₀ values of 4,1 mg/kg (5,85–19,36) in a neuropathic pain model through CCI. A dose of 30 mg/kg/24q was significantly effective in reducing mechanical allodynia 1 to 4h after treatment with nociception inhibition (145,83%). A reduction in the expression of hypoxia factors (HIF1α, Nrf2) was observed, along with an increase in antioxidant activity (CAT, SOD and GPX). Additionally, there was a reduction in inflammatory markes (IL_10, TNFα), microglial (IBA-1), and neuronal markers (NeuN, TACR1). Conclusion and clinical relevance: These findings demonstrate that the determined dose, administered daily for seven days, had an antinociceptive effect, as well as anti-inflammatory and antioxidant activity.

This study aimed to evaluate the therapeutic potential of amantadine in a vincristine-induced peripheral neuropathy model in rats. Forty-eight male Wistar rats were used. The treated groups received oral amantadine at doses of 2, 5, 12, 25 and 50 mg/kg, with daily applications for 14 days. The mechanical paw withdrawal threshold was measured using a digital analgesimeter. Immunohistochemical analysis of IL-6, TNFα, MIP1α, IL-10, CX3CR1, CXCR4, SOD, CAT and GPx, and enzymatic activity analysis of CAT, SOD and GPx were performed, in addition to quantitative PCR of Grp78, Chop, Ho1, Perk, Bax, Bcl-xL, Casp 3, Casp 9, IL-6, IL-10, IL-18 and IL-1β. The results showed an increase in nociceptive thresholds in animals that received 25 mg/kg and 50 mg/kg amantadine. Immunohistochemistry showed a decrease in the immunostaining of IL-6, TNFα, MIP1α and CX3CR1, and an increase in IL-10. CAT and SOD showed an increase in both immunochemistry and enzymatic analysis. qPCR revealed a reduced expression of genes related to endoplasmic reticulum stress and regulation in the expression of immunological and apoptotic markers. Amantadine demonstrated antinociceptive, anti-inflammatory and antioxidant effects in the vincristine-induced peripheral neuropathy model in rats, suggesting that amantadine may be considered an alternative approach for the treatment of vincristine-induced peripheral neuropathic pain.

Hypothyroidism compromises the testicular redox status and is associated with reduced sperm quality and infertility in men. In this regard, studies have demonstrated the antioxidant potential of kisspeptin in reproductive and metabolic diseases. In this study, we evaluate the effects of kisspeptin-10 (Kp10) on the testicular redox, as well as mediators of the unfolded protein response (UPR) in adult rats with hypothyroidism. Adult male Wistar rats were randomly separated into the Control (n = 15), Hypo (n = 13) and Hypo + Kp10 (n = 14) groups, and hypothyroidism was induced with 6-propyl-2-thiouracil (PTU) for three months. In the last month, half of the hypothyroid animals received Kp10. Testis samples were collected for enzymatic, immunohistochemical and/or gene evaluation of mediators of oxidative stress (TBARs, lipid hydroperoxides (LOOH), ROS, peroxynitrite, SOD, CAT and GPX), endoplasmic reticulum stress (GRP78, ATF6, PERK, CHOP, HO-1 and sXBP1) and antiapoptocytes (BCL-2). Hypothyroidism increased apoptosis index, TBARS and LOOH concentrations, and reduced testicular gene expression of Sod1, Sod2 and Gpx1, as well as the expression of Grp78, Atf6, Ho1 and Chop. Treatment with Kp10, in turn, reduced testicular apoptosis and the production of peroxynitrite, while increased SOD1 and GPX ½ expression, and enzymatic activity of CAT, but did not affect the lower expression of UPR mediators caused by hypothyroidism. This study demonstrated that hypothyroidism causes oxidative stress and dysregulated the UPR pathway in rat testes and that, although Kp10 does not influence the low expression of UPR mediators, it improves the testicular redox status, configuring it as an important antioxidant factor in situations of thyroid dysfunction.