Buprenorphine, but not lidocaine, effectively attenuates post-operative thermal hypersensitivity in an incisional model in neonatal rats (Rattus norvegicus)

There is limited information on safe and effective neonatal rodent analgesia. The aim of this study was to evaluate the efficacy and duration of analgesia provided by buprenorphine (Bup) and lidocaine (Lid) in an incisional pain model. Male and female postnatal day three Sprague Dawley rat pups (n=40) were randomly assigned to one of five treatment groups: 1) Saline - 0.1 ml subcutaneous (SC)/0.01 ml saline incisional infiltration; 2) BupL - 0.025 mg/kg Bup, SC/0.01 ml saline infiltration; 3) BupH - 0.05 mg/kg Bup, SC/0.01 ml saline infiltration; 4) LidL - 2 mg/kg lidocaine infiltration/0.1 ml saline SC; and 5) LidH - LDC 4 mg/kg lidocaine infiltration/0.1 ml saline SC. Rat pups were anesthetized with sevoflurane by mask, and a 1-cm full thickness skin incision was made over the left lateral thigh. Infiltration of lidocaine or saline occurred prior to wound closure with surgical glue. Baseline thermal latency was measured 24 hr prior to surgery, and subsequently 1, 2, 4, 8, 24, and 48-hrs post-operatively using an infrared diode laser. Thermal latency in the Saline group was significantly reduced compared to baseline up to the 4 hr timepoint. Both BupL and BupH attenuated thermal hypersensitivity for at least 4 hours in this model. LidL attenuated thermal hypersensitivity for 1 hr and LidH failed to attenuate thermal hypersensitivity. No abnormal clinical signs were noted for all treatment groups throughout the study. In summary, a single pre-operative dose of buprenorphine 0.025 to 0.05 mg/kg (SC) effectively attenuated postoperative thermal hypersensitivity in 3-day old neonatal rat incisional pain model for 4 hours

Mouse Anesthesia: The Art and Science

There is an art and science to performing mouse anesthesia, which is a significant component to animal research. Frequently, anesthesia is one vital step of many over the course of a research project spanning weeks, months, or beyond. It is critical to perform anesthesia according to the approved research protocol using appropriately handled and administered pharmaceutical-grade compounds whenever possible. Sufficient documentation of the anesthetic event and procedure should also be performed to meet the legal, ethical, and research reproducibility obligations. However, this regulatory and documentation process may lead to the use of a few possibly oversimplified anesthetic protocols used for mouse procedures and anesthesia. Although a frequently used anesthetic protocol may work perfectly for each mouse anesthetized, sometimes unexpected complications will arise, and quick adjustments to the anesthetic depth and support provided will be required. As an old saying goes, anesthesia is 99% boredom and 1% sheer terror. The purpose of this review article is to discuss the science of mouse anesthesia together with the art of applying these anesthetic techniques to provide readers with the knowledge needed for successful anesthetic procedures. The authors include experiences in mouse inhalant and injectable anesthesia, peri-anesthetic monitoring, specific procedures, and treating common complications. This article utilizes key points for easy access of important messages and authors’ recommendation based on the authors’ clinical experiences

Mouse Anesthesia: The Art and Science

There is an art and science to performing mouse anesthesia, which is a significant component to animal research. Frequently, anesthesia is one vital step of many over the course of a research project spanning weeks, months, or beyond. It is critical to perform anesthesia according to the approved research protocol using appropriately handled and administered pharmaceutical-grade compounds whenever possible. Sufficient documentation of the anesthetic event and procedure should also be performed to meet the legal, ethical, and research reproducibility obligations. However, this regulatory and documentation process may lead to the use of a few possibly oversimplified anesthetic protocols used for mouse procedures and anesthesia. Although a frequently used anesthetic protocol may work perfectly for each mouse anesthetized, sometimes unexpected complications will arise, and quick adjustments to the anesthetic depth and support provided will be required. As an old saying goes, anesthesia is 99% boredom and 1% sheer terror. The purpose of this review article is to discuss the science of mouse anesthesia together with the art of applying these anesthetic techniques to provide readers with the knowledge needed for successful anesthetic procedures. The authors include experiences in mouse inhalant and injectable anesthesia, peri-anesthetic monitoring, specific procedures, and treating common complications. This article utilizes key points for easy access of important messages and authors\u27 recommendation based on the authors\u27 clinical experiences

Differential effects of four intramuscular sedatives on cardiorespiratory stability in juvenile guinea pigs (Cavia porcellus)

Background Non-invasive physiological monitoring can induce stress in laboratory animals. Sedation reduces the level of restraint required, thereby improving the validity of physiological signals measured. However, sedatives may alter physiological equilibrium introducing unintended bias and/or, masking the experimental outcomes of interest. We aimed to investigate the cardiorespiratory effects of four short-acting sedatives in juvenile guinea pigs. Method 12 healthy, 38 (26–46) day-old Dunkin Hartley guinea pigs were included in this blinded, randomised, crossover design study. Animals were sedated by intramuscular injection using pre-established minimum effective doses of either alfaxalone (5 mg/kg), diazepam (5 mg/kg), ketamine (30 mg/kg), or midazolam (2 mg/kg) administered in random order with a minimum washout period of 48 hours between agents. Sedative depth, a composite score comprised of five assessment criteria, was observed every 5-min from dosing until arousal. Physiological monitoring of cardiorespiratory status included measures of heart rate, blood pressure, respiratory rate, and peripheral microvascular perfusion. Results Ketamine and alfaxalone were most effective in inducing stable sedation suitable for physiological monitoring, and diazepam less-so. Midazolam was unsuitable due to excessive hypersensitivity. All sedatives significantly increased heart rate above non-sedated control rates (P<0.0001), without altering blood pressure or microvascular perfusion. Alfaxalone and ketamine reduced respiratory rate relative to their control condition (P<0.0001, P = 0.05, respectively), but within normative ranges. Conclusion Ketamine and alfaxalone are the most effective sedatives for inducing short duration, stable sedation with minimal cardiorespiratory depression in guinea pigs, while diazepam is less-so. However, alfaxalone is the most appropriate sedative for longitudinal studies requiring multiple physiological timepoints

Substance P induces gastric mucosal protection at supraspinal level via increasing the level of endomorphin-2 in rats.

The aim of the present study was to analyze the potential role of substance P (SP) in gastric mucosal defense and to clarify the receptors and mechanisms that may be involved in it. Gastric ulceration was induced by oral administration of acidified ethanol in male Wistar rats. Mucosal levels of calcitonin gene-related peptide (CGRP) and somatostatin were determined by radioimmunoassay. For analysis of gastric motor activity the rubber balloon method was used. We found that central (intracerebroventricular) injection of SP (9.3-74pmol) dose-dependently inhibited the formation of ethanol-induced ulcers, while intravenously injected SP (0.37-7.4nmol/kg) had no effect. The mucosal protective effect of SP was inhibited by pretreatment with neurokinin 1-, neurokinin 2-, neurokinin 3- and mu-opioid receptor antagonists, while delta- and kappa-opioid receptor antagonists had no effect. Endomorphin-2 antiserum also antagonized the SP-induced mucosal protection. In the gastroprotective dose range SP failed to influence the gastric motor activity. Inhibition of muscarinic cholinergic receptors, or the synthesis of nitric oxide or prostaglandins significantly reduced the effect of SP. In addition, centrally injected SP reversed the ethanol-induced reduction of gastric mucosal CGRP content. It can be concluded, that SP may induce gastric mucosal protection initiated centrally. Its protective effect is likely to be mediated by endomorphin-2, and vagal nerve may convey the centrally initiated protection to the periphery, where both prostaglandins, nitric oxide and CGRP are involved in mediating this effect

Bupivacaine as a euthanasia agent for African Clawed Frogs (Xenopus laevis).

Immersion in tricaine methanesulfonate (i.e. TMS) has been used for euthanasia of Xenopus laevis (African Clawed frogs). However, the time for preparation and potential human health hazards may pose as a barrier for large group culls. Here, we aimed to investigate whether immersion in bupivacaine is an effective means to euthanize this species. In experiment one, frogs (n = 10/group) were randomly assigned to 1-h immersion in 1 of 3 treatment groups: 1) TMS-5 (MS-222, 5g/L); 2) TMS-10 (MS-222, 10 g/L); or 3) Bupi-1.5 (0.5% Bupivacaine, 1.5 g/L). Frogs were then removed from solutions, rinsed with system water, and placed into a recovery cage. Heart rate was evaluated audibly via doppler ultrasound flow over 1 min at immediate removal (T1h), at 2 (T2h), and 3 (T3h) h in the recovery cage. In experiment two, frogs (n = 7/group) underwent 5-h & 19-h immersion in either TMS-5 or Bupi-1.5, with heart rate assessment at 5 and 19 hrs. Righting reflex and withdrawal reflex of the hindlimb were tested during the experiments. Experiment one-after the 1-h immersion, Bupi-1.5 treated animals had decreased heart rates compared to TMS-5 and TMS-10 treated animals by T2h. Neither TMS-5, TMS-10, nor Bupi-1.5 ceased heart rate after the 1-h immersion. Experiment two-after the 5-h immersion, Bupi-1.5 and TMS-5 treated animals were comparable in heart rates. 43% of TMS-5 animals and 14% of the Bupi-1.5 animals had completely ceased heart rates at T5h. At 19 h all remaining animals exhibited rigor mortis and had ceased heart rate. We recommend 19-h of immersion using either TMS-5 or Bupi-1.5 for cessation of heart rate in African Clawed frogs. These data are strong support for the use of secondary physical methods for euthanasia in African Clawed frogs when euthanasia by immersion is performed

Sustained release buprenorphine effectively attenuates postoperative hypersensitivity in an incisional pain model in neonatal rats (Rattus norvegicus).

Despite the need for safe and effective postoperative analgesia in neonates, research regarding pain management in neonatal rodents is relatively limited. Here, we investigate whether sustained release buprenorphine (Bup SR) effectively attenuates thermal hypersensitivity in a neonatal rat model of incisional pain. Male and female postnatal day 3 Sprague Dawley rat pups (n = 34) were randomly assigned to one of four treatment groups: 1) saline (control), 0.1 mL, once subcutaneously (SC); 2) buprenorphine HCl (Bup HCl), 0.05 mg/kg, once SC; 3) low dose Bup SR (low-SR), 0.5 mg/kg, once SC; 4) high dose Bup SR (high-SR), 1 mg/kg, once SC. Pups were anesthetized with sevoflurane and a 0.5-cm long skin incision was made over the left lateral thigh. The underlying muscle was dissected and closed using surgical glue. Thermal hypersensitivity testing was performed at 24 h prior to surgery and subsequently at 1, 4, 8, 24, and 48 h post-surgery using an infrared diode laser. Thermal hypersensitivity was attenuated at 1 h post-surgery in the Bup HCl group, while it was attenuated through the entire postoperative period in both low-SR and high-SR groups. This data suggests that a single dose of low-SR (0.5 mg/kg) or high-SR (1 mg/kg) effectively attenuates thermal hypersensitivity for at least 8 h in neonatal rat pups