A case report of CBD and THC as analgesic therapy in a cat with chronic osteoarthritic pain.

A 10-year-old mixed breed male cat presented with clinical signs related to chronic orthopaedic pain. Upon physical examination, pain was noted, based on the feline Musculoskeletal Pain Index (FMPI). An analgesic treatment with a full spectrum cannabis oil (1.8% CBD and 0.8% THC) was proposed for 30 days (0,5 mg/kg based on CBD). The FMPI scale score decreased more than 50%. This case reported a satisfactory outcome for the patient and the owner, although this medication could increase ALT. Given the paucity of literature published to date on the treatment of veterinary species with cannabis-based medications, further clinical and pharmacokinetic studies are necessary to study the safety and efficacy of its use.

Characterisation of the in vivo interactions between detomidine and methadone in horses: Pharmacokinetic and pharmacodynamic modelling.

BACKGROUND: Pharmacokinetic (PK)/pharmacodynamic (PD) modelling offers new insights to design protocols for sedation and analgesia in standing horses. OBJECTIVES: To evaluate the parameters and interactions between detomidine and methadone when given alone or combined in standing horses. STUDY DESIGN: Randomised, placebo-controlled, blinded, crossover. METHODS: Eight adult healthy horses were given six treatments intravenously: saline (SAL); detomidine (5 µg/kg bwt; DET); methadone (0.2 mg/kg bwt; MET) alone or combined with detomidine (2.5 [MLD], 5 [MMD] or 10 [MHD] µg/kg bwt). Venous blood samples were obtained at predetermined times between 0 and 360 min after drug administration. Plasma detomidine and methadone were measured using a single, liquid/liquid extraction technique by liquid chromatography coupled with a triple quadrupole mass spectrometer (LC-MS/MS). Sequential PK/PD modelling compared rival models, with and without PK and PD interaction between drugs, to fit the PD data including height of the head above the ground (HHAG), a visual analogue scale for sedation (VAS), electrical (ET), thermal (TT) and mechanical (MT) nociceptive thresholds and gastrointestinal motility (GIM) [1]. RESULTS: Two and three compartment models best described the PK of detomidine and methadone, respectively. Detomidine decreased its own clearance as well as the clearance of methadone. The interaction of methadone on the effect of detomidine revealed an infra-additive (partial antagonism) effect for HHAG (α = -1.33), VAS (α = -0.98) and GIM (α = -1.05), a positive potentiation for ET (pot = 0.0041) and TT (pot = 0.133) and a synergistic to additive effect for MT (α = 0.78). MAIN LIMITATIONS: This is a small experimental study. CONCLUSIONS: Different PK/PD interactions were demonstrated for each PD parameter and could be modelled in vivo. The modelling of our data will allow us to simulate and predict the effect of constant rate infusions of both drugs for future investigations.

Sedation or anaesthesia decrease the stress response to electroejaculation and improve the quality of the collected semen in goat bucks.

Electroejaculation (EE) is stressful and probably painful; thus the administration of anaesthesia is recommended to decrease those negative effects. However, anaesthesia has a direct risk of provoking death, but sedation is less risky than anaesthesia. At the same time, α2-adrenergic agonists may improve semen quality. Therefore, the aim of the present study was to compare the physiological and behavioural responses indicative of stress and possibly pain, and the semen quality in electroejaculated untreated, anaesthetised or sedated goat bucks. Semen was collected from eight bucks using three different procedures in all them (EE in untreated bucks, EE under sedation or EE under general anaesthesia). The number of vocalizations during EE and the behavioural pattern before and after procedures were recorded. Pain visual analogue scale (VAS) score was also determined during EE. Rectal temperature, heart rate, serum cortisol concentration, biochemical and haematological parameters were measured before and after each procedure, and sperm characteristics were determined. Bucks vocalised more often when untreated than sedated or anaesthetised (P<0.02). The pain VAS score was greater when bucks were untreated than sedated or anaesthetised (P<0.002). The rectal temperature, heart rate, total protein, albumin and haemoglobin concentrations were greater when bucks were untreated than anaesthetised or sedated (P<0.02). Serum cortisol increased after EE (P=0.0006), without differences between procedures. The frequency and duration of lying down after EE were greater when bucks were anaesthetised than sedated or untreated (P<0.05), and were also greater when bucks were sedated than untreated (P<0.05). The number of times that the animal tried to stand up after EE was greater when bucks were anaesthetised than sedated or untreated (P<0.02). The sperm mass motility was greater when bucks were anaesthetised or sedated than when they were untreated (P=0.048). When animals were sedated, the ejaculate contained more spermatozoa with functional plasma membrane (P=0.03) and morphologically normal (P=0.05) than when they were untreated. In conclusion, general anaesthesia and sedation decreased the stress and probably the pain response provoked by EE and especially sedation improved the quality of the semen collected.

Pharmacokinetics and pharmacodynamics of the injectable formulation of methadone hydrochloride and methadone in lipid nanocarriers administered orally to horses.

We investigated the thermal, electrical and mechanical antinociceptive and physiological effects (heart rate, respiratory rate, arterial blood pressure, head height and abdominal auscultation score), and pharmacokinetics, of 0.5 mg/kg of the injectable formulation (ORAL) or nanoparticulated methadone (NANO) given orally, in six adult mares, using a crossover, blind and prospective design. Repeated-measure models were used to compare parametric data between and within treatments, followed by Tukey's test. Nonparametric data were analysed with Wilcoxon signed-rank, adjusted by Bonferroni tests. Blood samples were also collected up to 6 h after dosing for plasma drug quantification by LC-MS/MS. Methadone pharmacokinetic parameters were determined by noncompartmental and compartmental approaches. There were no differences in pharmacodynamic parameters. No statistical differences were observed in the pharmacokinetic parameters from noncompartmental analysis for both groups, except a significant decrease in peak plasma concentration, increase in apparent volume of distribution per fraction absorbed (Vdss /F) and increased mean residence time (MRT) for NANO. One-compartment open model with first order elimination best described the pharmacokinetic profiles for both groups. Neither ORAL nor NANO administered orally to horses produced antinociception. The nanoencapsulated formulation of methadone given orally to horses did not improve methadone pharmacokinetic parameters or increased systemic body exposure to methadone.

Diagnostic value of computed tomography, radiography and ultrasonography in metacarpophalangeal joint disorders in horses / Importância diagnóstica da tomografia computadorizada, radiografia e ultrassonografia nas afecções da articulação metacarpofalangeana em equinos

In modern society the work and athletic performance of horses has led to a very important animal production sector in which Brazil possesses the third largest horse stock. Among all equine lesions described, metacarpophalangeal (fetlock) joint lesions are considered one of the main causes of lameness. Consequently, there is a need to improve the understanding and diagnosis of these injuries. The most efficient imaging diagnostic methods for the fetlock region are computed tomography, radiography and ultrasound. Imaging studies of the anatomical structures involving this joint are extremely important to obtain a more precise diagnose. The present study was performed in order to evaluate the capacity of different imaging diagnostic modalities to detect a variety of lesions in different fetlock structures. Twenty horses (Equus caballus) used for horsemanship activities were referred to the Department of Animal Reproduction and Veterinary Radiology of São Paulo State University, Botucatu campus, with clinical signs of metacarpophalangeal joint injuries. Horses were submitted to radiographic and ultrasonographic exam and computed tomography scan. Image analysis revealed a significant capacity of these methods to characterize lesions in this region. However, computed tomography provided broader and better evaluation of lesions in bones and adjacent structures, because it allows the analysis to be performed on three-dimensional projections, with attenuation coefficients (window selections) and tissue density measurement through Hounsfield Units (HU).

As atividades desempenhadas pelo cavalo na sociedade contemporânea são diversas, e o Brasil é portador do terceiro maior plantel mundial de equinos. Entre as várias afecções descritas em cavalos atletas, as lesões na articulação metacarpofalangeana (boleto) são consideradas as principais causas de claudicação. Por isso, continuamente se aprofunda o conhecimento no diagnóstico das enfermidades que acometem essa região. Dentre as modalidades de diagnóstico por imagem, os exames de tomografia computadorizada, radiografia e ultrassonografia constituem os mais eficazes para avaliação da região do boleto. Com o presente trabalho, teve-se como objetivo avaliar o desempenho da tomografia computadorizada, da radiografia e da ultrassonografia nas mais variadas injúrias das estruturas da articulação metacarpofalangeana. Vinte cavalos (Equus caballus), destinados às atividades de horsemanship, foram encaminhados ao Departamento de Reprodução Animal e Radiologia Veterinária da Universidade Estadual Paulista, campus de Botucatu, com sinais clínicos de afecções na articulação metacarpofalangeana. Os animais foram submetidos aos exames de radiografia, ultrassonografia e tomografia computadorizada. As imagens revelaram grande capacidade dos métodos em caracterizar lesões nessa articulação. Entretanto, a tomografia computadorizada possibilitou avaliar de modo mais amplo e aprimorado as lesões em estruturas ósseas e adjacentes dessa articulação, pois permite a análise das imagens por meio de projeções tridimensionais, a seleção de coeficiente de atenuação e a mensuração da densidade dos tecidos em unidade Hounsfield (HU).

Antinociceptive effects of methadone combined with detomidine or acepromazine in horses.

REASONS FOR PERFORMING STUDY: To investigate two protocols to provide antinociception in horses. OBJECTIVES: To evaluate the antinociceptive effects of intravenous methadone combined with detomidine or acepromazine in adult horses. STUDY DESIGN: Randomised, blinded, crossover study. METHODS: Mechanical, thermal and electrical stimuli were applied to the dorsal left and right metacarpus and coronary band of the left thoracic limb, respectively. A thermal stimulus was applied caudal to the withers. The horses were treated with saline (C), a combination of methadone (0.2 mg/kg bwt) and detomidine (10 µg/kg bwt) (MD) or methadone (0.2 mg/kg bwt) and acepromazine (0.05 mg/kg bwt) (MA) at 1 week intervals. Nociceptive thresholds were measured before and at 15 min intervals until 150 min after treatment. Wilcoxon rank-sum and Wilcoxon signed rank tests were used to compare data between groups at each time point and over time within each group, followed by the Bonferroni method to adjust the P value. RESULTS: The mechanical stimulus was the most sensitive test to differentiate the antinociceptive effects of the treatments. Mechanical thresholds were greater after MD than MA between 15 and 30 min and with both MD and MA these thresholds were greater than C from 15 to 60 min. Electrical and thermal limb thresholds were greater after MD than C at 15 and 45 min and at 15, 30, 45, 75 and 105 min, respectively. Thermal limb thresholds were greater with MA than C at 30 min. Thoracic thermal threshold in MD and MA were higher than C at 45, 75, 90 and 120 min and from 30 to 75 min, respectively. CONCLUSIONS: Methadone and acepromazine produced less pronounced mechanical antinociception than MD.

Validation of mechanical, electrical and thermal nociceptive stimulation methods in horses.

REASONS FOR PERFORMING STUDY: To validate a model for investigating the effects of analgesic drugs on mechanical, thermal and electrical stimulation testing. OBJECTIVES: To investigate repeatability, sensitivity and specificity of nociceptive tests. STUDY DESIGN: Randomised experiment with 2 observers in 2 phases. METHODS: Mechanical (M), thermal (TL) and electrical (E) stimuli were applied to the dorsal metacarpus (M-left and TL-right) and coronary band of the left thoracic limb (E) and a thoracic thermal stimulus (TT) was applied caudal to the withers in 8 horses (405 ± 43 kg). Stimuli intensities were increased until a clear avoidance response was detected without exceeding 20 N (M), 60°C (TL and TT) and 15 V (E). For each set of tests, 3 real stimuli and one sham stimulus were applied (32 per animal) using a blinded, randomised, crossover design repeated after 6 months. A distribution frequency and, for each stimulus, Chi-square and McNemar tests compared both the proportion of positive responses detected by 2 observers and the 2 study phases. The κ coefficients estimated interobserver agreement in determining endpoints. Sensitivity (384 tests) and specificity (128 tests) were evaluated for each nociceptive stimulus to assess the evaluators' accuracy in detecting real and sham stimuli. RESULTS: Nociceptive thresholds were 3.1 ± 2 N (M), 8.1 ± 3.8 V (E), 51.4 ± 5.5°C (TL) and 55.2 ± 5.3°C (TT). The level of agreement after all tests, M, E, TL and TT, was 90, 100, 84, 98 and 75%, respectively. Sensitivity was 89, 100, 89, 98 and 70% and specificity 92, 97, 88, 91 and 94%, respectively. CONCLUSIONS: The high interobserver agreement, sensitivity and specificity suggest that M, E and TL tests are valid for pain studies in horses and are suitable tools for investigating antinociceptive effects of analgesics in horses.