Effects of intra-articular anesthesia of the tarsometatarsal joint on skin sensation of the distal limb in horses.

Objective: To determine with mechanical nociceptive threshold (MNT) testing whether distal limb skin sensation is affected by intra-articular anesthesia of the tarsometatarsal joint (TMTJ). Animals and procedure: This was a prospective cohort study. Ten client-owned horses that had intra-articular TMTJ anesthesia were included in the study. The MNT was measured at 6 sites on the distal limb at 3 time points: before anesthesia (T0) and at 10 min (T10) and 30 min (T30) post-injection. Linear mixed-model analyses were done, with the significance level set at P < 0.05. Results: There was an increase in MNT (P = 0.001) across combined testing points between T0 and T30, indicating loss of skin sensation in the distal limb 30 min after TMTJ anesthesia. Regarding individual MNT sites, there were increases at the lateral proximal sesamoid bone (P = 0.002) and dorsal coronary band (P = 0.037) at T30 compared to T0. Conclusion: Intra-articular anesthesia of the TMTJ significantly increased the combined MNT of the skin of the distal limb at 30 min, indicating decreased skin sensation. Clinical relevance: Diagnostic anesthesia of the distal hind limb should be performed before TMTJ block. However, if patient compliance prevents this, lameness evaluation 10 min after blocking may enhance the reliability of interpretation.

Effets de l'anesthésie intra-articulaire de l'articulation tarsométatarsienne sur la sensation cutanée du membre distal chez le cheval. Objectif: Déterminer à l'aide d'un test de seuil nociceptif mécanique (MNT) si la sensation cutanée du membre distal est affectée par l'anesthésie intra-articulaire de l'articulation tarsométatarsienne (ATMT). Animaux et procédure: Il s'agissait d'une étude de cohorte prospective. Dix chevaux appartenant à des clients et ayant subi une anesthésie intra-articulaire pour l'ATMT ont été inclus dans l'étude. Le MNT a été mesuré sur 6 sites du membre distal à 3 moments: avant l'anesthésie (T0) et à 10 min (T10) et 30 min (T30) après l'injection. Des analyses linéaires sur modèles mixtes ont été effectuées, avec le niveau de signification fixé à P < 0,05. Résultats: Il y avait une augmentation du MNT (P = 0,001) sur tous les points de test combinés entre T0 et T30, indiquant une perte de sensation cutanée dans le membre distal 30 minutes après l'anesthésie du ATMT. En ce qui concerne les sites MNT individuels, il y avait des augmentations au niveau de l'os sésamoïde proximal latéral (P = 0,002) et de la bande coronaire dorsale (P = 0,037) à T30 par rapport à T0. Conclusion: L'anesthésie intra-articulaire du ATMT a augmenté de manière significative le MNT combiné de la peau du membre distal à 30 min, indiquant une diminution de la sensation cutanée. Pertinence clinique: Une anesthésie diagnostique du membre postérieur distal doit être réalisée avant le bloc de l'ATMT. Cependant, si l'observance du patient l'empêche, l'évaluation de la boiterie 10 minutes après le blocage peut améliorer la fiabilité de l'interprétation.(Traduit par Dr Serge Messier).

Impact of arthroscopy on post-procedure intra-articular elbow injections: A cadaveric study.

OBJECTIVE: To determine the influence of arthroscopy and injection volume on post-procedure intra-articular (IA) injection extravasation. STUDY DESIGN: Ex vivo prospective study. SAMPLE POPULATION: A total of 40 paired canine cadaver forelimbs. METHODS: After radiographs and computed tomography (CT) scans with three-dimensional (3D) digital bone model reconstructions, elbows were randomly assigned to the arthroscopy or control group and randomly assigned to receive an IA injection of 2 or 4 mL of contrast. Elbow arthroscopy was performed on assigned specimens, followed by IA injections of contrast in all elbows, and imaging was repeated. 3D digital model volumes were compared. Images were interpreted and scored for extravasation by a radiologist unaware of treatment and volume assignments. RESULTS: Based on CT images and regardless of treatment group, IA injections of 4 mL resulted in a mean extravasation score of 2.25 (SD 0.97) versus 1.55 (SD 1.05) (p = .02) for 2 mL IA injections. The change in 3D model volumes after IA injections was a mean of 13.2 cm3 (SD 5.85) after 4 mL injections, compared to 6.97 cm3 (SD 6.28) (p = .003) after 2 mL injections. On radiographic evaluation, but not CT, the mean extravasation scores were 2.45 (SD 1.15) for the arthroscopy group and 1.25 (SD 0.79) for the control group (p < .001). CONCLUSION: A larger volume of IA injection resulted in higher CT extravasation scores and larger 3D volumes regardless of arthroscopic treatment. CLINICAL SIGNIFICANCE: IA injections performed immediately after arthroscopy resulted in 50% or less extravasation, especially with a smaller IA injection volume.

Pharmacokinetics of intraarticular liposomal amphotericin B in goats (Capra aegagrus hircus).

Lameness is a significant welfare concern in goats. Amphotericin B is used via intraarticular (IA) administration in models to study experimentally induced lameness in large animals. The main objective of this study was to estimate plasma pharmacokinetic (PK) parameters for amphotericin B in goats after a single IA administration. Liposomal amphotericin B was administered to ten Kiko-cross goats at a dose of 10 mg total (range: 0.34-0.51 mg/kg) via IA administration into the right hind lateral distal interphalangeal joint. Plasma samples were collected over 96 h. Amphotericin B concentrations were measured via liquid chromatography/mass spectrometry (LC-MS/MS). A non-compartmental analysis was used to derive PK parameters. Following single IA administration, maximum plasma concentration was estimated at 54.6 ± 16.5 ng/mL, and time to maximum concentration ranged from 6 to 12 h. Elimination half-life was estimated at 30.9 ± 16.5 h, and mean residence time was 45.1 ± 10.4 h. The volume of distribution after IA administration was 13.3 ± 9.4 L/kg. The area under the curve was 1481 ± 761 h*ng/mL. The achieved maximum concentration was less than the observed concentrations for other species and routes of administration. Further research is needed into the pharmacodynamics of IA liposomal amphotericin B in goats to determine specific research strategies.

Pharmacokinetics of amikacin after intravenous, intra-articular, and combined intravenous and intra-articular administration in healthy neonatal foals.

BACKGROUND: Pharmacokinetics of amikacin administered IV to neonatal foals are described, but little data are available regarding the plasma concentrations contributed by concurrent intra-articular (IA) administration. HYPOTHESIS/OBJECTIVES: Compare the pharmacokinetics of amikacin when the total dose is administered IV compared to being divided between IV and IA routes of administration in neonatal foals and predict the plasma concentrations from various combined IV and IA dosing regimens. ANIMALS: Eight healthy neonatal foals. METHODS: Foals received 3 amikacin treatment protocols: (1) IV-only (25 mg/kg q24h IV), (2) concurrent IV and IA (16.7 mg/kg q24h IV and 8.3 mg/kg q24h into 1 tarsocrural joint), and (3) IA-only (8.3 mg/kg q24h into 1 tarsocrural joint). Protocols were administered for 3 days beginning at 7, 14, and 21 days of age. Plasma concentrations ≥53 µg/mL at 30 minutes were considered therapeutic for isolates with intermediate susceptibility. RESULTS: Foal age was a significant variable. The IV-only protocol met or exceeded the 30-minute plasma concentrations considered therapeutic (mean µg/mL [95% confidence interval, CI]) in 7- to 9-day-old (54.0 [52.2-56.9]), 14- to 16-day-old (58.1 [55.2-61.0]), and 21- to 23-day-old (66.6 [63.7-69.6]) foals. Concurrent IV and IA protocol did not reach the 30-minute concentration considered therapeutic in 7- to 9-day-old foals (46.5 [43.6-49.4]) but did in 14- to 16-day-old (62.9 [60.0-65.8]) and 21-to 23-day-old (62.6 [59.7-65.6]) foals. CONCLUSIONS AND CLINICAL IMPORTANCE: Concurrent IV and IA administration of amikacin produces 30-minute plasma concentrations considered therapeutic in foals 14 to 23 days old, but concentrations observed in younger foals might be below those considered therapeutic for isolates with intermediate susceptibility to amikacin.

Serial injections of 4% polyacrylamide hydrogel have no detrimental effects in equine joints following clinical, histologic, and synovial biomarker evaluation.

OBJECTIVE: Polyacrylamide hydrogel (4% PAHG) is an inert viscoelastic supplement used to manage osteoarthritis in horses. Even with a prolonged clinical effect, horses may be administered multiple doses during their performance career. The effect of the serial 4% PAHG treatments is not known. The objectives of this study were to evaluate the clinical, histologic, and synovial fluid biomarker effects following serial administration of 4% PAHG in normal equine fetlock joints. ANIMALS: 8 healthy horses. METHODS: In a blinded, controlled in vivo study, horses received serial intra-articular injections of 4% PAHG (Noltrex Vet; Nucleus ProVets LLC) and contralateral 0.9% saline control on days 0, 45, 90, and 135. Treatment and control joints were randomly assigned. Synovial fluid was collected before administration of 4% PAHG or 0.9% saline on day 0 and at study completion for cellular and biomarker evaluation. Serial physical and lameness examinations were performed throughout the study. On day 240, gross examination and harvest of cartilage and synovial membrane for histology were completed. RESULTS: There were no histologic changes in articular cartilage or synovial fluid biomarkers. The 4% PAHG was seen on the surface of the synovium in 5 of 8 treated joints 105 days after the last treatment. There are minimal effects following serial injections of 4% PAHG on normal joints in horses following administration at 0, 45, 90, and 135 days, with final evaluation on day 240. CLINICAL RELEVANCE: Serial administration of intra-articular 4% PAHG in horses may provide long-term joint lubrication with no detrimental effects.

Allogeneic chondrogenic-induced mesenchymal stem cells for the treatment of tarsometatarsal lameness in horses.

OBJECTIVE: To assess the efficacy of commercial intra-articular blood-derived allogeneic-induced mesenchymal stem cells (CIMSCs) to treat tarsometatarsal lameness in horses. STUDY DESIGN: This was a retrospective cohort study. ANIMALS: Records from 167 adult light breed horses with bilateral tarsometatarsal lameness. METHODS: Horses with tarsometatarsal lameness were retrospectively selected from medical records. Diagnosis followed subjective graded lameness assessment before and after intra-articular analgesia, with graded radiographic tarsal examination. Horses were excluded if they were diagnosed or treated for any other concurrent lameness conditions during the study. Time to last follow-up and time of recurrence of lameness was recorded at veterinary re-assessment. RESULTS: A total of 67 horses were recruited to the CIMSC-treated group and 100 to the corticosteroid (CS)-treated group. Median age was 9 years, with no difference in signalment, use or radiographic grade between groups. First re-examination was 38 days (95% CI: 38-49), with no difference between groups, CIMSC 42 (35-45), control 34 (25-42). Median follow-up was 438 days for CIMSC, 546 for controls. Symptoms of lameness recurred in 86/100 controls compared to 17/67 (25%) CIMSC. Median time to lameness recurring in CIMSC was 336 days (95% CI: 239-400), control 90 days (95% CI: 80-108), p < .0001. Cox proportional hazard ratio for treatment was 8.35, 95% CI: 4.67 to 14.92, p < .0001. CONCLUSIONS: Lameness was abolished in all treated horses. It recurred significantly less often, and later, in CIMSC-treated horses. CLINICAL SIGNIFICANCE: Intra-articular CIMSC treatment results in prolonged soundness in horses with tarsometatarsal lameness.

Intra-articular triamcinolone acetonide injection results in increases in systemic insulin and glucose concentrations in horses without insulin dysregulation.

BACKGROUND: Corticosteroids are a commonly used, inexpensive intra-articular treatment for osteoarthritis which may increase the risk for laminitis in horses due, in part, to hyperinsulinaemia. Humans with metabolic syndrome experience increases in insulin and glucose concentrations post-injection, but responses in horses are unknown. OBJECTIVES: To determine the effect of a single intra-articular (IA) dose of triamcinolone acetate (TA) on blood insulin and glucose concentrations. STUDY DESIGN: Before-after study. METHODS: Ten horses with normal insulin regulation as assessed by an oral sugar test received 18 mg of TA into one middle carpal joint. Insulin and glucose concentrations were evaluated at baseline and 4, 6, 8, 24, 48, and 72 h following IA corticosteroid injection. Differences from baseline were evaluated using a repeated measures ANOVA with Dunnett's multiple comparison testing or a Friedman test with Dunn's correction (significant at p < 0.05). RESULTS: Mean ± SD blood insulin concentration post IA TA injection was increased at 6 h (15.8 ± 3.1 µIU/mL, p = 0.01), 24 h (23 ± 5.8 µIU/mL, p ≤ 0.001), and 48 h (29 ± 13 µIU/mL, p ≤ 0.01) compared to baseline (10 ± 12.3 µIU/mL), with the peak at 48 h. Median ± 95% CI blood glucose concentration post IA TA injection was increased at 6 h (112.7 ± 20.3 mg/dL, p = 0.006), 8 h (112.9 ± 21.4 mg/dL, p = 0.004), 24 h (122.6 ± 14.6, p ≤ 0.0001), and 48 h (123.5 ± 15.4 mg/dL, p ≤ 0.0001) compared to baseline (89.2 ± 6.6 mg/dL), with the peak at 48 h. MAIN LIMITATIONS: Only horses with normal insulin regulation were evaluated. CONCLUSIONS: Blood insulin and glucose concentrations modestly increased for 48 h following IA TA.

Insertional biceps tendinopathy palliated successfully with intra-articular triamcinolone acetonide injection in a dog: A case report.

This report describes a dog diagnosed with insertional biceps tendinopathy that was palliated with intra-articular triamcinolone acetonide injections. The patient was a 6-year-old spayed female Chihuahua dog that had left thoracic limb lameness for 3 months before presentation. On physical examination, moderate pain was elicited by performing the biceps test and isolated full elbow extension on the left thoracic limb. Gait analysis showed asymmetrical peak vertical force and vertical impulse between thoracic limbs. Computed tomography (CT) revealed enthesophyte formation on the ulnar tuberosity of the left elbow joint. Ultrasonography showed a heterogeneous fibre pattern at the biceps tendon insertion site on the left elbow joint. These findings confirmed insertional biceps tendinopathy based on physical examination, CT and ultrasonography results. The dog received an intra-articular triamcinolone acetonide injection with hyaluronic acid in the left elbow joint. Clinical signs improved after the first injection, including a range of motion, pain and gait. A second injection was given in the same manner because of recurring mild lameness 3 months later. No clinical signs were observed during the follow-up period.

Intravenous Injection of Equine Mesenchymal Stem Cells in Dogs with Articular Pain and Lameness: A Feasibility Study.

Osteoarthritis is a frequently occurring joint disorder in veterinary practice. Current treatments are focused on pain and inflammation; however, these are not able to reverse the pathological condition. Mesenchymal stem cells (MSCs) could provide an interesting alternative because of their immunomodulatory properties. The objective of this study was to evaluate the potential of a single intravenous (IV) injection of xenogeneic equine peripheral blood-derived MSCs (epbMSCs) as treatment for articular pain and lameness. Patients with chronic articular pain were injected intravenously with epbMSCs. They were evaluated at three time points (baseline and two follow-ups) by a veterinarian based on an orthopedic joint assessment and an owner canine brief pain inventory scoring. Thirty-five dogs were included in the safety and efficacy evaluation of the study. Results showed that the epbMSC therapy was well tolerated, with no treatment-related adverse events and no increase in articular heat or pain. A significant improvement in lameness, range of motion, joint effusion, pain severity, and interference scores was found 6 weeks post-treatment compared with baseline. This study demonstrates that future research on IV administration of epbMSCs is warranted to further explore its possible beneficial effects in dogs with chronic articular pain and lameness. Clinical Trial gov ID: EC_2018_002.

Effects of a Single Intra-Articular Injection of 2% Lidocaine or 0.5% Bupivacaine on Synovial Fluid Acute Phase Protein Concentrations in Healthy Horses.

The purpose of this study was to compare the extent of inflammation response in the middle carpal joints of healthy horses following intra-articular injection of 2% lidocaine, 0.5% bupivacaine, or 0.9% saline solution. The right middle carpal joint of 20 horses was injected with 5 mL of 0.5% bupivacaine (GB, n = 10) or 5 mL of 2% lidocaine (GL, n = 10). The left middle carpal joint of horses was used as a control (5 mL 0.9% saline). Serum and synovial fluid (SF) were aseptically collected before and at predetermined times after each injection. Serum and synovial fluid protein, albumin, transferrin, haptoglobin, ceruloplasmin, α1-antitripsin, and α1-acid glycoprotein concentrations were measured by sodium dodecyl sulfate polyacrylamide gel electrophoresis and compared among treatments. The results were submitted to analysis of variance using the SAS statistical program, and means were compared by the Student-Newman-Keuls test (P < .05). Both lidocaine and bupivacaine induced serum and SF changes indicative of inflammation, but the magnitude of those changes was more pronounced for lidocaine. Administration of 0.9% saline also induced an inflammatory reaction, but the magnitude of these changes was less pronounced than those caused by GB and GL. The results suggested that bupivacaine is safer than lidocaine for intra-articular injection in horses. Saline solution should not be used as an adjunct to intra-articular injections in horses.

Pharmacokinetics of intra-articular buprenorphine in horses with lipopolysaccharide-induced synovitis.

The objective of this study was to describe the pharmacokinetics of intra-articular (IA) administered buprenorphine in horses with lipopolysaccharide (LPS)-induced synovitis. Radiocarpal synovitis was induced in six healthy adult horses with the IA injection of LPS (0.5 ng/joint) on two occasions in a randomized cross-over design. Treatments (IA buprenorphine (IAB) at 5 µg/kg plus intravenous saline; and intravenous buprenorphine (IVB) at 5 µg/kg plus IA saline) were administered 4 h following LPS injection. Concentrations of buprenorphine were assessed in plasma and synovial fluid (SF) at 0.5, 2, 6, 12, and 24 h after administration. Pharmacokinetic parameters after IVB and IAB in plasma and synovial fluid were calculated using a nonlinear mixed effects model. IAB was detectable in SF of all horses at 24 h [median concentration of 6.2 (3.46-22.6) ng/mL]. IAB resulted in a median plasma concentration of 0.59 (0.42-1.68) ng/mL at 0.5 h and was detectable in all subjects for up to 6 h and in two horses for up to 12 h. IVB resulted in SF concentrations detected up to 6 h in all horses [median concentration of 0.12 (0.07-0.82) ng/mL]. Results suggest that IA buprenorphine remains present in the inflamed joint for at least 24 h and systemic absorption occurs.

Effects of intra-articular injection of an acellular equine liquid amniotic allograft in healthy equine joints.

OBJECTIVE: Evaluate effects of acellular equine liquid amnion allograft (ELAA) injected into healthy equine joints. STUDY DESIGN: Randomized, blinded, controlled experiment. ANIMALS: Eight healthy adult horses. METHODS: One intercarpal joint (ICJ) of each horse was randomly assigned to be injected with 1.5 ml of ELAA (treatment) while the contralateral ICJ was injected with 1.5 ml of 0.9% NaCl (control). Subjective lameness evaluation, force plate analysis, and synovial fluid analysis, including interleukin-1 receptor antagonist (IL-1ra) analysis, were performed before (day 0) and at days 1, 3, 5, and 10. Synovial fluid analysis was also performed on days 20 and 30. RESULTS: No difference in subjective lameness (P = .75) and no decrease in peak vertical force or vertical impulse were seen in any limb on any day. Total nucleated cell count (TNCC) was increased in treatment joints on days 1 (P = .0007; T: 6039 cells/µl, C: 240 cells/µl) and 3 (P < .0001; T: 1119 cells/µl, C: 240 cells/µl). Log-10 transformed values for IL-1ra were higher in treated joints on days 1 (P = .0005; T: 3553.7 pg/ml, C: 1890.1 pg/ml) and 3 (P = .01; T: 2283.2 pg/ml, C: 1250.7 pg/ml). CONCLUSION: Injection of ELAA into the ICJ caused an increase in synovial fluid TNCC in comparison with saline control but no lameness was observed. There was increased IL-1ra on days 1 and 3 after ELAA injection. CLINICAL SIGNIFICANCE: Intra-articular injection of ELAA into healthy equine joints results in no significant safety concerns. The observed increase in IL-1ra may provide beneficial effects in inflamed joints.

Evaluating the Safety of Intra-Articular Mitotherapy in the Equine Model: A Potential Novel Treatment for Osteoarthritis.

No current treatments available halt osteoarthritis progression in horses or humans. Intra-articular injection of mitochondria is a novel treatment that has the potential to improve cell metabolism and decrease inflammation, but safety of this treatment has yet to be established in the horse. Autologous blood-derived mitochondria isolated using a commercially available kit were injected into the left carpus joint of 3 horses which were monitored for 28 days. Horses received physical examinations, video recorded gait evaluations, joint diameter measurement, synovial fluid collection, and blood collection on day 0 (baseline prior to mitotherapy, day of mitochondria injection), 1, 3, 7, 14, and 28. Systemic inflammation was assessed via complete blood count, fibrinogen, and plasma serum amyloid A (SAA). Local inflammation was assessed via synovial fluid cytology and physical examination parameters. Physical exam parameters remained stable and no joint swelling was observed after mitotherapy. No change was noted in video recorded gait evaluations as determined by a blinded evaluator. Complete blood counts revealed no significant increase in white blood cells. SAA only increased mildly in 1 horse. Fibrinogen became slightly elevated above reference range in 2 horses at day 7, but later normalized. Mild increases in synovial fluid nucleated cell counts and total protein occurred on day 1 and 3, but resolved within 7 days without intervention. Autologous mitochondria injection into the equine intercarpal joint was well tolerated with no signs of inflammation. This safety information allows for future studies evaluating mitotherapy efficacy.

Residual effects of intra-articular betamethasone and triamcinolone acetonide in an equine acute synovitis model.

BACKGROUND: Intra-articular (IA) corticosteroids are regularly used in equine athletes for the control of joint inflammation. OBJECTIVES: The goal of this study was to use an acute synovitis inflammation model to determine the residual effects of IA betamethasone and triamcinolone acetonide on various inflammatory parameters and lameness. STUDY DESIGN: Crossover randomised trial. METHODS: Five mixed-breed, 2-year-old horses were randomly allocated to an IA treatment of the radiocarpal joint with 9 mg of either betamethasone or triamcinolone acetonide. Two weeks following treatment, horses were injected with 1 µg of lipopolysaccharide (LPS) diluted in 1 ml of saline. Following LPS injection, horses were crossed-over and both sets of injections were repeated after a washout period. Blood samples were collected at multiple time points for mRNA analysis, as well as serum amyloid A (SAA) and cortisol determination. At each time point, lameness was also subjectively scored. Additional injections with saline-only or LPS-only (twice) were conducted as negative and positive controls, respectively. Two-way repeated measures analysis of variance was used to analyse all data. RESULTS: Corticosteroid-only treatments result in significant mRNA expression differences, as well as significant and prolonged cortisol suppression. Following LPS injection, there was a residual treatment effect with triamcinolone evidenced by a significant treatment effect on IL-6 and PTGS1 (cyclooxygenase-1), lameness, SAA and cortisol concentrations, while only IL-6 expression was affected by betamethasone. MAIN LIMITATIONS: The acute synovitis model used here results in significant inflammation and is not representative of the low-grade inflammation seen with typical joint disease and residual anti-inflammatory effects may be more profound in naturally occurring joint disease. CONCLUSIONS: Current regulatory guidelines may be insufficient if the concern is residual anti-inflammatory effects. Additionally, intra-articular corticosteroid administration is not without risk, as evidenced by a significant suppression of serum cortisol concentration and, as such, the benefits of their administration should be weighed against those risks.

Objective evaluation for analgesia of the distal interphalangeal joint, the navicular bursa and perineural analgesia in horses with naturally occurring forelimb lameness localised to the foot.

BACKGROUND: The outcome and interpretation of intra-synovial diagnostic analgesia of the distal interphalangeal joint (DIPJ) and the navicular bursa (NB) remain in dispute, and no objective studies have been carried out to establish the percentage of improvement over time from these two analgesia techniques. OBJECTIVES: To investigate the qualitative and time-dependent outcome of DIPJ-A and NB-A in naturally occurring forelimb lameness. STUDY DESIGN: Case series. METHODS: Twenty-three clinical cases with forelimb lameness were evaluated objectively using a body mounted inertial sensor system (BMIS). Lameness was localised to the foot with a palmar digital nerve block and/or an abaxial sesamoidean nerve block on day 1, and analgesia of the DIPJ (DIPJ-A) and NB (NB-A) were performed on days 2 and 3. Improvement following perineural analgesia was measured after 10 min and intra-synovial blocks after 2-, 5- and 10-min. Horses with at least 70% improvement measured objectively after diagnostic analgesia were included in the study. RESULTS: There was no significant association between improvement following perineural analgesia and the DIPJ-A and NB-A. The mean improvement in the lameness differed between DIPJ-A and NB-A at 2 min (p < 0.001) and at 5 min (p = 0.04), and it was no longer observed after 10 min (p = 0.06). A positive NB-A produced a high degree of improvement that remained stable, whereas the DIPJ-A improved over time. MAIN LIMITATIONS: Perineural and intra-synovial analgesia were performed without contrast medium to assess the diffusion of mepivacaine. CONCLUSIONS: Our results suggest that perineural analgesia is not reliable enough to differentiate pain originating from DIPJ and NB. Early evaluation of the DIPJ-A and NB-A can determine the origin of the pain. An improvement following NB-A was constant over time, but an improvement following DIPJ-A varied by up to 10 min.

Pharmacokinetics and pharmacodynamics of intra-articular isoflupredone following administration to horses with lipopolysaccharide-induced synovitis.

BACKGROUND: Intra-articular corticosteroids, such as isoflupredone acetate, are commonly used in the treatment of joint inflammation, especially in performance horses. Following administration in a non-inflamed joints blood concentrations of isoflupredone were low and detectable for only a short period of time post-administration compared to synovial fluid concentrations. For some drugs, inflammation can affect pharmacokinetics, therefore, the goal of the current study was to describe the pharmacokinetics of isoflupredone acetate following intra-articular administration using a model of acute synovitis. Secondarily, pharmacodynamic effects, including effects on joint circumference, joint flexion, and lameness following intra-articular administration of isoflupredone acetate in the experimental model were described. METHODS: Sixteen horses received a single intra-articular dose of 8 mg of isoflupredone acetate or saline 12 h post-administration of lipopolysaccharide. Blood and urine samples were collected up to 72 h and synovial fluid for 28 days post-administration, drug concentrations determined by liquid chromatography- mass spectrometry and pharmacokinetic analysis performed. Joint circumference, maximum angle of pain free joint flexion and lameness were evaluated prior to and post-treatment. RESULTS: The maximum isoflupredone plasma concentration was 2.45 ± 0.61 ng/mL at 2.5 ± 0.75 h and concentrations were less than the limit of quantitation by 72 h. Isoflupredone was below detectable concentrations in urine by 72 h post-administration in all horses and no longer detectable in synovial fluid by 96 h post-administration. Joint circumference was significantly decreased in the isoflupredone treatment group compared to the saline group at 24 and 48 h post drug administration. Pain free joint flexion was significantly different between the saline and isoflupredone treatment groups on day 4 post-treatment. CONCLUSIONS: Synovial fluid concentrations and maximum plasma concentrations of isoflupredone differed slightly between the current study and a previous one describing administration into a non-inflamed joint, however, the detection time of isoflupredone in blood was comparable. Effects of isoflupredone on joint circumference and degree of pain free joint flexion suggest a short duration of effect with respect to alleviation of lipopolysaccharide induced synovitis, however, results of this study support future studies of the anti-inflammatory effects of intra-articular isoflupredone acetate.

Concentrations of dexmedetomidine and effect on biomarkers of cartilage toxicity following intra-articular administration in horses.

OBJECTIVE: The goal of this study was to determine plasma, urine, and synovial fluid concentrations and describe the effects on biomarkers of cartilage toxicity following intra-articular dexmedetomidine administration to horses. ANIMALS: 12 research horses. PROCEDURES: Horses received a single intra-articular administration of 1 µg/kg or 5 µg/kg dexmedetomidine or saline. Plasma, urine, and synovial fluid were collected prior to and up to 48 hours postadministration, and concentrations were determined. The effects on CS846 and C2C were determined in synovial fluid at 0, 12, and 24 hours postadministration using immunoassays. RESULTS: Plasma concentrations of dexmedetomidine fell below the limit of quantification (LOQ) (0.005 ng/mL) by 2.5 and 8 hours postadministration of 1 and 5 µg/kg, respectively. Synovial fluid concentrations were above the LOQ (0.1 ng/mL) of the assay at 24 hours in both dose groups. Drug was not detected in urine samples at any time postdrug administration. CS846 concentrations were significantly decreased relative to baseline at 12 hours postadministration in the saline group and significantly increased in the 5-µg/kg-dose group at 24 hours. Concentrations of C2C were significantly decreased at 12 and 24 hours postadministration in the saline treatment group. There were no significant differences in CS846 or C2C concentrations between dose groups at any time. CLINICAL RELEVANCE: Systemic concentrations of dexmedetomidine remained low, compared to synovial fluid concentrations. CS846, a marker of articular cartilage synthesis, increased in a dose-dependent fashion. Based on these findings, further dose titration and investigation of analgesic and adverse effects are warranted.