Analgesic effect of the mint terpenoid L-carvone in sheep

ObjectiveTo determine whether L-carvone increases the voltage threshold response to a noxious electrical stimulus in sheep.Study designProspective, blinded, randomized, crossover experimental study.AnimalsA group of six healthy adult sheep.MethodsSheep were instrumented with cranial dorsothoracic subcutaneous copper electrodes. A stimulator delivered a 10 ms square-wave stimulus at 50 pps starting at 0.1 V with a 0.2 V second^–1 ramp. The stimulus stopped once two observers who were blinded to treatment noted a behavioral pain response or when a 15 V cut-off was reached. Next, 0.15 mL kg^–1 of either a 50% L-carvone solution or a saline-vehicle control was administered intramuscularly, and electrical threshold responses were measured every 5–15 minutes over a 6 hour period using methods identical to the baseline. One week following the first treatment (L-carvone or control), sheep were studied using identical methods with the second treatment (control or L-carvone). Drug and time effects were evaluated using a two-way repeated measures analysis of variance, and pairwise comparisons were evaluated with Holm-Sidák tests with values of p < 0.05 considered significant.ResultsL-carvone significantly increased voltage threshold responses for most time points up to 75 minutes compared with baseline and with saline control. The last time point with a significantly different response between L-carvone and saline treatments was 5 hours after drug administration. The saline-vehicle control decreased voltage threshold responses at several time points after 3 hours.Conclusions and clinical relevanceIntramuscular L-carvone is analgesic in sheep, although the ethanol-propylene glycol vehicle may cause mild hyperalgesia. This study demonstrates that a food-derived compound can be used to relieve pain in a food-producing animal.     

Validation of a thermal threshold nociceptive model in bearded dragons (Pogona vitticeps)

Objectives

To validate a thermal threshold (TT) nociceptive model in bearded dragons (Pogona vitticeps) and to document TT changes after administration of morphine.

Caudal epidural anesthesia in mares after bicarbonate addition to a lidocaine–epinephrine combination

Objective

To investigate the nociceptive and clinical effects of buffering a lidocaine–epinephrine solution with sodium bicarbonate in caudal epidural block in mares.

Intraoperative nociception-antinociception monitors: A review from the veterinary perspective

ObjectiveTo review monitors currently available for the assessment of nociception-antinociception in veterinary medicine.Databases usedPubMed, Web of Science and Google Scholar. The results were initially filtered manually based on the title and the abstract.ConclusionsThe provision of adequate antinociception is difficult to achieve in veterinary anaesthesia. Currently, heart rate and arterial blood pressure are used to monitor the response to a noxious stimulus during anaesthesia, with minimum alveolar concentration-sparing effect and stress-related hormones used for this purpose in research studies. However, since none of these variables truly assess intraoperative nociception, several alternative monitoring devices have been developed for use in humans. These nociceptive-antinociceptive monitoring systems derive information from variables, such as electroencephalography, parasympathetic nervous system (PNS) response, sympathetic nervous system response and electromyography. Several of these monitoring systems have been investigated in veterinary medicine, although few have been used to assess intraoperative nociception in animals. There is controversy regarding their effectiveness and clinical use in animals. A nociceptive-antinociceptive monitoring system based on the PNS response has been developed for use in cats, dogs and horses. It uses the parasympathetic tone activity index, which is believed to detect inadequate intraoperative nociception-antinociception balance in veterinary anaesthesia. Nonetheless, there are limited published studies to date, and cardiovascular variables remain the gold standard. Consequently, further studies in this area are warranted.     

Modulation of nociceptive withdrawal reflexes evoked by single and repeated nociceptive stimuli in conscious dogs by low-dose acepromazine

ObjectivesTo investigate the modulation of the nociceptive withdrawal reflex (NWR) and temporal summation (TS) by low‐dose acepromazine (ACP) in conscious dogs. To assess the short‐ and long‐term stability of the reflex thresholds.Study designRandomized, blinded, placebo‐controlled cross‐over experimental study.AnimalsEight adult male Beagles.MethodsThe NWR was elicited using single transcutaneous electrical stimulation of the ulnar nerve. Repeated stimuli (10 pulses, 5 Hz) were applied to evoke TS. The responses of the deltoideus muscle were recorded and quantified by surface electromyography and the behavioural reactions were scored. Each dog received 0.01 mg kg^?1 ACP or an equal volume saline intravenously (IV) at 1 week intervals. Measurements were performed before (baseline) and 20, 60 and 100 minutes after drug administration. Sedation was scored before drug administration and then at 10 minutes intervals. Data were analyzed with Friedman repeated measures analysis of variance on ranks and Wilcoxon signed rank tests.ResultsAcepromazine resulted in a mild tranquilization becoming obvious at 20 minutes and peaking 30 minutes after injection. Single (I_t) and repeated stimuli (TS_t) threshold intensities, NWR and TS characteristics and behavioural responses were not affected by the ACP at any time point. Both I_t and TS_t were stable over time.Conclusions and clinical relevanceIn dogs, 0.01 mg kg^?1 ACP IV had no modulatory action on the NWR evoked by single or repeated stimuli, suggesting no antinociceptive activity on phasic nociceptive stimuli. The evidence of the stability of the NWR thresholds supports the use of the model as an objective tool to investigate nociception in conscious dogs. A low dose of ACP administered as the sole drug, can be used to facilitate the recordings in anxious subjects without altering the validity of this model.     

Intravenous tramadol: effects, nociceptive properties, and pharmacokinetics in horses

ObjectiveTo determine the optimal dose, serum concentrations and analgesic effects of intravenous (IV) tramadol in the horse.Study designTwo-phase blinded, randomized, prospective crossover trial.AnimalsSeven horses (median age 22.5 years and mean weight 565 kg).MethodsHorses were treated every 20 minutes with incremental doses of tramadol HCl (0.1–1.6 mg kg^?1) or with saline. Heart rate, respiratory rate, step frequency, head height, and sweating, trembling, borborygmus and head nodding scores were recorded before and up to 6 hours after treatment. In a second study, hoof withdrawal and skin twitch reflex latencies (HWRL and STRL) to a thermal stimulus were determined 5 and 30 minutes, and 1, 2, 4 and 6 hours after bolus IV tramadol (2.0 mg kg^?1) or vehicle. Blood samples were taken to determine pharmacokinetics.ResultsCompared to saline, tramadol caused no change in heart rate, step frequency or sweating score. Respiratory rate, head height, and head nodding and trembling scores were transiently but significantly increased and borborygmus score was decreased by high doses of tramadol. Following cumulative IV administration of 3.1 mg kg^?1 and bolus IV administration of 2 mg kg^?1, the elimination half-life of tramadol was 1.91 ± 0.33 and 2.1 ± 0.9 hours, respectively. Baseline HWRL and STRL were 4.16 ± 1.0 and 3.06 ± 0.99 seconds, respectively, and were not significantly prolonged by tramadol.Conclusion and clinical relevanceIV tramadol at cumulative doses of up to 3.1 mg kg^?1 produced minimal transient side effects but 2.0 mg kg^?1 did not provide analgesia, as determined by response to a thermal nociceptive stimulus.     

Evaluation of a regional nerve block with an experimental formulation of encapsulated lidocaine in sheep

ObjectiveTo compare the duration of nociceptive and proprioceptive blockade from an experimental encapsulated lidocaine preparation with that of conventional lidocaine.Study designProspective, blinded, randomly assigned, crossover study.AnimalsA total of six adult Dorset ewes, American Society of Anesthesiologists physical status I or II, weighing 60.4 ± 18.0 kg (mean ± standard deviation).MethodsUnder general anesthesia and guided by electrolocation, the common peroneal nerve was blocked unilaterally with encapsulated lidocaine (0.1 mL kg^–1, 200 mg mL^–1) or conventional lidocaine hydrochloride (0.1 mL kg^–1, 20 mg mL^–1). Each sheep was administered both treatments with an interval of 2 weeks between treatments. Nociception and proprioception were scored (scales of 0–3) before anesthesia, at 0.5, 1, 2, 4, 8, 12, 16, 20 and 24 hours after completion of local anesthetic injection, and every 12 hours thereafter for 9 days. Nociceptive and proprioceptive blockade ended the first time each score reached ‘0’; maximum blockade duration was considered and recorded to be the time point immediately prior to this end point. Significance of differences between treatments for duration of blockade was tested with the Wilcoxon rank-sum test. Effects of time and treatment on nociceptive and proprioceptive blockade were evaluated with mixed-effect models. Significance was set at p < 0.05.ResultsCompared with conventional lidocaine, nociceptive blockade lasted 88 hours longer with encapsulated lidocaine (p = 0.008), and proprioceptive blockade lasted 6 hours longer (p = 0.03). Significant effects of time (p < 0.0001), treatment (p = 0.0435) and treatment1time (p < 0.0001) were observed for nociception. Significant effects of time (p < 0.0001) and treatment1time (p = 0.0058) were observed for proprioception.ConclusionEncapsulated lidocaine produced nociceptive blockade with a duration substantially longer than conventional lidocaine.Clinical relevanceSustained-release encapsulated lidocaine alleviates pain and may minimize systemic analgesic use.     

Comparative analgesic and sedative effects of tramadol,tramadol‐lidocaine and lidocaine for caudal epidural analgesia in donkeys (Equus asinus)

ObjectiveTo compare anti-nociceptive and sedative effects of tramadol, a combination of tramadol-lidocaine, and lidocaine alone for perineal analgesia in donkeys.Study designExperimental ‘blinded’ randomized cross-over study.AnimalsSix healthy adult donkeys.MethodsTreatments were tramadol (TR) (1.0 mg kg⁻¹), tramadol-lidocaine (TRLD) (0.5 and 0.2 mg kg⁻¹ respectively) and lidocaine (LD) (0.4 mg kg⁻¹) given into the epidural space. The volume of all treatments was 0.02 mL kg⁻¹. Nociception was tested at the perineal region by pin prick, followed, if no reaction, by pressure from a haemostat clamp. Times to onset, degree and duration of anti-nociception of the perineal region were recorded. Response was tested immediately after drug administration and at: 2, 5, 10, 15, 30, 45, and 60 minutes post-administration and then at 30 minute intervals thereafter until a response re-occurred. Physiologic data and degree of sedation and ataxia were recorded pre-administration and at intervals for 240 minutes post-administration. Results were analyzed using anova, Kruskal–Wallis tests, and Wilks’ Lambda test as relevant. Significance was taken as p < 0.05.ResultsTimes (minutes, mean ± SD) to onset and duration of anti-nociception, respectively were; TR 13 ± 1.6 and 220 ± 4.6; TRLD 6 ± 0.8 and 180 ± 8.5; LD 4 ± 1.4 and 75 ± 4. Onset and duration times were significantly longer with TR than the other two treatments. TR never produced complete anti-nociception, whereas the TRLD and LD induced complete anti-nociceptive effects. Duration was significantly longer with TRLD than with LD alone. Epidural injections of TR and TRLD induced mild sedation.Conclusions and clinical relevanceEpidural combination of TRLD produced an anti-nociceptive effect in the perineum, which was rapid in onset and had a longer duration of action than LD alone. An epidural single dose of TRLD combination would appear to provide an acceptable analgesic effect in the perineal region of donkeys.     

The effect of social isolation,gender and familiarity with the experimental procedure on tests of porcine nociceptive thresholds

ObjectiveTo investigate the effects of habituation and isolation on mechanical nociceptive thresholds in pigs at the pelvic limbs and at the tail.Study designProspective randomized multifactorial study.AnimalsThirty-two healthy castrated male (experiment 1), and 12 castrated male and 12 female (experiment 2) Danish Landrace × Yorkshire pigs, weighing 63.5 ± 0.8 kg and 55.4 ± 0.6 kg (the mean ± SD, experiment 1 and 2, respectively).MethodsMechanical nociceptive thresholds were quantified with a von Frey anesthesiometer applied to two distinct anatomical regions (tail and pelvic limbs). Pigs receiving the mechanical challenge in the pelvic limbs were tested inside a cage, whereas pigs exposed to stimuli at the tail region were tested in an open arena. For both experiments, the effect of familiarity to the procedure was evaluated by comparing thresholds of nociception in habituated versus naïve pigs. The presence of a companion animal was also evaluated in pigs receiving stimuli at the pelvic limbs.ResultsPigs tested inside the cage were affected by the habituation to the procedure as indicated by the increase in willingness and time spent by the animals in the test cage. This effect was reflected in the lower mechanical nociceptive thresholds (medians with 25–75 percentiles) recorded for familiar pigs compared with naïve animals [495 g (302–675) versus 745 g (479–1000), respectively; p = 0.026]. Mechanical nociceptive thresholds measured at the tail of the pigs in the open arena were not affected by the familiarity of the animals with the experimental procedure.Conclusions and clinical relevanceThe current results reiterate the value of habituation in research involving animal behaviour. Further characterization of the methodology is needed to allow its application in the evaluation of clinical conditions in pigs.