Heat hypersensitivity at a site proximal to a surgically induced osteochondral fracture in horses.

OBJECTIVE: To evaluate thermal nociceptive thresholds (TNTs) before and after inducing a standardized radiocarpal bone osteochondral fracture (OCF) in horses. STUDY DESIGN: Prospective, controlled, randomized, masked study. ANIMALS: A group of 10 Thoroughbred fillies aged 2 years. METHODS: Skin temperature and TNTs were measured on the skin over the triceps brachii muscle in both the thoracic limbs before (week 0) and weekly (weeks 1-8) after unilateral arthroscopic induction of a radiocarpal OCF (n = 4) or sham surgery (n = 6) followed by a standardized exercise programme. The contralateral, non-operated thoracic limb was used as a control within each horse. Percentage thermal excursion (%TE) defined as %TE = 100 ∗ (TNT - skin temperature)/(cut-off temperature - skin temperature) was calculated. Data were analysed with a mixed-effects model followed by Dunnett's and Tukey's tests for within and between-limbs comparisons, respectively; p < 0.05 was considered significant. RESULTS: Skin temperature in the control limb of OCF horses was significantly higher at week 7 than at week 0 (p = 0.0125). At week 1, TNTs and %TE values in operated limbs of OCF horses were significantly reduced compared with their baseline values at week 0 (p ≤ 0.0153) and their values in contralateral control limbs (p ≤ 0.0024) and operated limbs of sham-operated horses (p ≤ 0.0162). At week 2, TNTs and %TE values in operated limbs of OCF horses remained significantly reduced compared with values in operated limbs of sham-operated horses (p ≤ 0.0248). CONCLUSIONS AND CLINICAL RELEVANCE: Creation of an OCF in a radiocarpal bone induced transitory (<2 weeks) ipsilateral heat hypersensitivity proximal to the surgery site (skin over the triceps brachii muscle) in horses. Surgically induced OCF may cause somatosensory abnormalities consistent with secondary thermal hyperalgesia.

Electroencephalographic responses of anaesthetized pigs (Sus scrofa) to tail docking using clippers or cautery iron performed at 2 or 20 days of age.

OBJECTIVE: To compare electroencephalographic (EEG) responses of pigs to tail docking using clippers or cautery iron, performed at 2 or 20 days of age. STUDY DESIGN: Prospective, randomised controlled experimental study. ANIMALS: A total of 40 Large White x Landrace entire male pigs aged 2 (n=20) or 20 (n=20) days were randomly assigned to undergo tail docking using clippers or cautery iron. METHODS: Anaesthesia was induced and maintained with halothane delivered in oxygen. Following instrumentation, end-tidal halothane concentration was stabilised at 1.0±0.05%, and EEG recording commenced. After a 5 minute baseline period, tail docking was performed and recording continued for additional 10 minutes. EEG data were subjected to Fast Fourier transformation, yielding the summary variables median frequency (F50), 95% spectral edge frequency (F95) and total power (PTOT). Variables recorded during the baseline period were compared with those calculated at consecutive 15 second intervals following tail docking. RESULTS: Following tail docking, F50 decreased briefly but significantly in 2-day-olds, whereas 20-day-olds exhibited a sustained increase in F50 (p<0.05). Immediately after tail docking, F50 was overall lower in 2-day-olds than in 20-day-olds (p<0.05). F95 increased after docking in 20-day-olds docked using clippers (p<0.05) but did not change in 20-day-olds docked using cautery iron or in 2-day-olds docked using either method. Overall, F95 was lower in 2-day-olds than in 20-day-olds from 30 to 60 seconds after docking (p<0.05). PTOT decreased after docking in 20-day-olds (p<0.05) but did not change in 2-day-olds. Overall, PTOT was lower in 2- than in 20-day-olds during baseline and after tail docking (p<0.05). CONCLUSIONS AND CLINICAL RELEVANCE: These data suggest that tail docking using clippers is more acutely painful than docking using cautery iron and that docking within the first days of birth may be less acutely painful than docking at a later age.

Assessment of a carbon dioxide laser for the measurement of thermal nociceptive thresholds following intramuscular administration of analgesic drugs in pain-free female cats.

OBJECTIVE: To assess the potential of a thermal carbon dioxide (CO2) laser to explore antinociception in pain-free cats. STUDY DESIGN: Experimental, prospective, blinded, randomized study. ANIMALS: Sixty healthy adult female cats with a (mean±standard deviation) weight of 3.3±0.6 kg. METHODS: Cats were systematically allocated to one of six treatments: saline 0.2 mL per cat; morphine 0.5 mg kg(-1); buprenorphine 20 µg kg(-1); medetomidine 2 µg kg(-1); tramadol 2 mg kg(-1), and ketoprofen 2 mg kg(-1). Latency to respond to thermal stimulation was assessed at baseline and at intervals of 15-30, 30-45, 45-60, 60-75, 90-105 and 120-135 minutes. Thermal thresholds were assessed using time to respond behaviourally to stimulation with a 500 mW CO2 laser. Within-treatment differences in response latency were assessed using Friedman's test. Differences amongst treatments were assessed using independent Kruskal-Wallis tests. Where significant effects were identified, pairwise comparisons were conducted to elucidate the direction of the effect. RESULTS: Cats treated with morphine (χ2=12.90, df=6, p=0.045) and tramadol (χ2=20.28, df=6, p=0.002) showed significant increases in latency to respond. However, subsequent pairwise comparisons indicated that differences in latencies at specific time-points were significant (p<0.05) only for tramadol at 60-75 and 90-105 minutes after administration (21.9 and 43.6 seconds, respectively) in comparison with baseline (11.0 seconds). No significant pairwise comparisons were found within the morphine treatment. Injections of saline, ketoprofen, medetomidine or buprenorphine showed no significant effect on latency to respond. CONCLUSIONS AND CLINICAL RELEVANCE: The CO2 laser technique may have utility in the assessment of thermal nociceptive thresholds in pain-free cats after analgesic administration and may provide a simpler alternative to existing systems. Further exploration is required to examine its sensitivity and comparative utility.

Trans-pinnal movement of methimazole: an in vitro study showing that methimazole can cross from the inner to outer pinna of cats.

OBJECTIVES: The aim of the study was to determine if methimazole applied in a transdermal formulation to the internal pinna will cross to the external pinna in an in vitro Franz cell model. METHODS: The ears from six cats were harvested soon after death. Whole ears were mounted onto Franz-type diffusion cells with the stratum corneum of the inner pinnae uppermost. A commercial transdermal preparation containing methimazole (0.1 ml/10 mg) was applied to the inner pinnae. At 1, 2, 4, 6, 8, 12, 18, 24 and 30 h, a 200 µl sample of reservoir solution was removed to determine the methimazole concentration by high-performance liquid chromatography. The ears were then dissected, separating the internal pinna from the cartilage and the external pinna, before the methimazole concentration was measured at each site. The thickness of the different regions of the ear was measured on paraffin histology sections. RESULTS: Mean ± SD methimazole concentrations at 30 h for the right and left ear, respectively, were: inner ear, 1.25 ± 0.53 mg/g, 0.39 ± 0.26 mg/g; cartilage, 1.36 ± 0.47 mg/g, 0.33 ± 0.20 mg/g; and outer ear, 1.0 ± 0.32 mg/g, 0.33 ± 0.14 mg/g. There was a difference between the left and right ears (P <0.001). Minimal methimazole concentrations were detected in the receptor fluid. The mean methimazole concentration absorbed by the skin after application of 10 mg was, for the right ear, 3.65 ± 1.27 mg/g and, for the left, 1.08 ± 0.27 mg/g. There was no correlation between methimazole concentrations and thickness of each region of the ear. CONCLUSIONS AND RELEVANCE: Methimazole in a lipophilic vehicle applied to the inner pinna will penetrate to the outer pinna of cats in an in vitro model, which may have safety implications for humans associated with cats treated with transdermal methimazole. Substantial inter-individual variation was found. Further research is required in the area of transdermal penetration of drugs in cats.

Characterisation of mixing in the proximal duodenum of the rat during longitudinal contractions and comparison with a fluid mechanical model based on spatiotemporal motility data.

The understanding of mixing and mass transfers of nutrients and drugs in the small intestine is of prime importance in creating formulations that manipulate absorption and digestibility. We characterised mixing using a dye tracer methodology during spontaneous longitudinal contractions, i.e. pendular activity, in 10 cm segments of living proximal duodenum of the rat maintained ex-vivo. The residence time distribution (RTD) of the tracer was equivalent to that generated by a small number (8) of continuous stirred tank reactors in series. Fluid mechanical modelling, that was based on real sequences of longitudinal contractions, predicted that dispersion should occur mainly in the periphery of the lumen. Comparison with the experimental RTD showed that centriluminal dispersion was accurately simulated whilst peripheral dispersion was underestimated. The results therefore highlighted the potential importance of micro-phenomena such as microfolding of the intestinal mucosa in peripheral mixing. We conclude that macro-scale modeling of intestinal flow is useful in simulating centriluminal mixing, whereas multi-scales strategies must be developed to accurately model mixing and mass transfers at the periphery of the lumen.

Prevention of N-methyl-D-aspartate-induced mechanical nociception by intrathecal administration of ketoprofen and ketamine in sheep.

BACKGROUND: Nonsteroidal antiinflammatory drugs and N-methyl-D-aspartate (NMDA) receptor antagonists reduce pain hypersensitivity when given by the intrathecal (i.t.) route, but their combined effects have hardly been studied. We assessed the effects of the nonsteroidal antiinflammatory drug ketoprofen and the NMDA receptor channel blocker ketamine, given alone and in combination, on mechanical nociceptive thresholds in sheep implanted with indwelling cervical i.t. catheters. METHODS: Sheep were given, by i.t. catheter, ketoprofen (200-3200 microM; 100 microL) and ketamine (25-400 microM; 100 microL) alone or in combination (837.95-3350.78 microM; 100 microL; 0.955:0.045 proportion). They also received NMDA (2 mM; 100 microL) preceded by the highest concentration of ketoprofen and ketamine alone or in combination. Saline solution (0.9%; 100 microL) and xylazine (1.95 mM; 100 microL) were used as negative and positive controls, respectively. RESULTS: Xylazine significantly increased the area under the nociceptive threshold versus time curve values (AUC) for 30, 60, and 180 min posttreatment. Ketoprofen and ketamine, alone and in combination, produced no significant effect on AUC values. NMDA alone decreased the AUC value for 30 min posttreatment. This pain hypersensitivity was prevented by preadministering ketoprofen and ketamine alone and in combination. CONCLUSIONS: In sheep, i.t. administration of ketoprofen and ketamine, alone or together, produced no hypoalgesia; however, they prevented NMDA-induced mechanical hypersensitivity. Ketoprofen and ketamine may have therapeutic potential in conditions associated with persistent pain.