Analgesic and anti-hyperalgesic effects of epidural morphine in an equine LPS-induced acute synovitis model

Epidural morphine is widely used in veterinary medicine, but there is no information about the anti-hyperalgesic and anti-inflammatory effects in acute inflammatory joint disease in horses. The analgesic, anti-hyperalgesic and anti-inflammatory effects of epidural morphine (100mg/animal or 0.17±0.02mg/kg) were therefore investigated in horses with acute synovitis. In a cross-over study, synovitis was induced in the talocrural joint by intra-articular lipopolysaccharide (LPS). The effect of epidural morphine was evaluated using physiological, kinematic and behavioural variables. Ranges of motion (ROM) of the metatarsophalangeal and talocrural joints were measured, clinical lameness scores and mechanical nociceptive thresholds (MNTs) were assessed and synovial fluid inflammatory markers were measured. The injection of LPS induced transient synovitis, resulting in clinical lameness, decreased ranges of motion in the talocrural and metatarsophalangeal joints, decreased limb loading at rest and increased composite pain scores. Epidural morphine resulted in a significant improvement in clinical lameness, increased ROM and improved loading of the LPS-injected limb at rest, with no effects on synovial fluid inflammatory markers. Morphine prevented a decrease in MNT and, hence, inhibited the development of hyperalgesia close to the dorsal aspect of inflamed talocrural joints. This study showed that epidural morphine provides analgesic and anti-hyperalgesic effects in horses with acute synovitis, without exerting peripheral anti-inflammatory effects.     

Pain control in horses: What do we really know?

Currently, approaches to pain control in horses are a mixture of art and science. Recognition of overt pain behaviours, such as rolling, kicking at the abdomen, flank watching, lameness or blepharospasm, may be obvious; subtle signs of pain can include changes in facial expression or head position, location in the stall and response to palpation or human interaction. Nonsteroidal anti‐inflammatory drugs (i.e. phenylbutazone, flunixin meglumine and firocoxib), opioids (i.e. butorphanol, morphine and buprenorphine) and α₂‐adrenergic agonists (i.e. xylazine, detomidine, romifidine and medetomidine) are the most commonly used therapeutic options. Multimodal therapy using constant‐rate infusions of lidocaine, ketamine and/or butorphanol has gained popularity for severe pain in hospitalised cases. Drugs targeting neuropathic pain, such as gabapentin, are increasingly used for conditions such as laminitis. Optimal strategies for management of pain are based upon severity and chronicity, including special considerations for use of intra‐articular or epidural delivery and therapy in foals. Strategies that aim to mitigate adverse effects associated with use of various analgesic agents are briefly discussed.     

Use of ethanol in the treatment of distal tarsal joint osteoarthritis: 24 cases

Reasons for performing this study: Intra‐articular ethanol has been described to promote distal tarsal joint ankylosis. Its use and results in clinical cases affected by osteoarthritis (OA) have not been reported. Objectives: To describe and evaluate the results of treatment of distal tarsal joint OA by facilitated ankylosis stimulated by intra‐articular ethanol injection. Methods: Twenty‐four horses met the inclusion criteria of tarsometatarsal and centrodistal joint OA diagnosed by a positive response to intra‐articular analgesia, radiographic evaluation and recurrence of lameness ≤4 months after intra‐articular medication with a corticosteroid. Horses were sedated and, following a radiographic contrast study of the tarsometatarsal joint, medication with 2–4 ml of either 100% pure ethanol (G100) or a 70% ethanol (G70) solution was applied. Horses were classified as improved based on a 50% reduction from initial lameness grade combined with an increase in exercise level. Results: Of the 24 horses included in this study, 20 had the treatment performed bilaterally and 4 unilaterally. All horses were available for initial follow‐up examination and 21 for a second one 6–9 months after treatment. This represented a total of 44 treated limbs and 35 available for long‐term follow‐up. Of these, 21/35 (60%) were considered improved, which corresponds to 11/21 horses (52%). Of 21 horses, 4 (19%) deteriorated and 2 of these developed significant complications related to treatment. Conclusions: Distal tarsal joint ankylosis with ethanol should be considered a safe and economic treatment in cases of distal tarsal joint OA that fail to show long‐term improvement with intra‐articular corticosteroid treatment. Potential relevance: Ethanol should be considered in the treatment of certain cases of distal tarsal joint OA. The importance of performing an adequate radiographic contrast study of the tarsometatarsal joint prior to treatment is highlighted.     

Idiopathic haemarthrosis in eight horses

Objectives To review eight horses diagnosed with idiopathic haemarthrosis and to describe the intra‐articular use of yttrium‐90 (⁹⁰Y) and methylprednisolone acetate (MPA) in recurrent haemarthrosis cases. Design Retrospective case series. Method The medical records, diagnostic images, histopathology and outcome of all horses diagnosed with idiopathic haemarthrosis between 1998 and 2010 were reviewed. Results Four Thoroughbred racehorses with haemarthrosis of the antebrachiocarpal joint had severe acute lameness (median, grade 4) and marked joint effusion after high‐speed exercise. Another four horses (2 Thoroughbred racehorses, 1 Standardbred racehorse, 1 Warmblood) had haemarthrosis of the tarsocrural joint and presented with mild, intermittent lameness (median, grade 1) and marked, persistent joint effusion. Six of the eight horses had recurrent haemarthrosis prior to treatment. Radiographic and nuclear scintigraphic examinations did not identify bone pathology. Diagnostic arthroscopy (7 cases) identified grossly hypertrophied yellow/brown discoloured synovium. Synovial histopathology of these cases revealed chronic synovial hyperplasia with severe haemosiderosis and granulomatous inflammatory reaction of varying severity. All horses underwent rest, bandaging and phenylbutazone administration. Two horses had subtotal mechanical synovectomy, four horses had intra‐articular administration of ⁹⁰Y and MPA, and one horse underwent both treatments. Seven cases returned to their previous use (median time, 7 months). Haemarthrosis recurred in three horses, two of which had received the ⁹⁰Y and MPA treatment. Conclusion Idiopathic haemarthrosis should be considered a differential for acute and recurrent joint related lameness and effusion. Recurrence appears not uncommon and the use of intra‐articular ⁹⁰Y and MPA in conjunction with a conservative management treatment protocol warrants further evaluation.     

Diagnosis and management of Candida utilis infectious arthritis in a Standardbred filly

A 3‐year‐old Standardbred filly was admitted to the hospital for evaluation and management of previously diagnosed infectious arthritis of the right metacarpophalangeal joint (MCPJ). Candida utilis was isolated from multiple synovial samples submitted for bacterial culture and susceptibility. Following treatment with systemic and intra‐articular fluconazole and regional limb perfusion with amphotericin B and a second arthroscopic debridement the lameness improved and subsequent cultures were negative for bacterial or fungal growth. Infectious fungal arthritis should be a differential diagnosis for atypical or unresponsive joint infections especially in horses previously treated with a combination of intra‐articular corticosteroids and antibiotics.     

Pharmacological evaluation of a selective bradykinin B1 antagonist in a canine model of arthritis

The effects of a selective bradykinin 1 receptor antagonist, compound A, were evaluated in a canine model of acute inflammatory model of arthritis. Despite detection of the B₁ receptor in canine type B synoviocytes using a fluorescent ligand, oral administration of compound A (9 and 27 mg/kg) did not improve weight bearing of dogs injected intra‐articularly with IL‐1β in a force plate analysis. Analysis of the synovial fluid of IL‐1β‐treated dogs indicated high levels of bradykinin postchallenge. Excellent exposure, coupled with evidence of the presence of the B₁ receptor during an acute inflammatory model of pain, indicates an inability of the receptor to mediate inflammatory pain in canines.     

Is there a relationship between clinical presentation,diagnostic and radiographic findings and outcome in horses with osteoarthritis of the small tarsal joints?

Reasons for performing study: Despite the possibility that sound horses may have radiographic signs consistent with osteoarthritis of the small tarsal joints (OA‐STJ), a diagnosis of ‘bone spavin’ as a cause of lameness is often made based only on radiographic examination. Objectives: To determine whether severity of radiographic change and response to treatment are correlated with the duration and degree of lameness and the response to intra‐articular anaesthesia in horses with OA‐STJ. Methods: A retrospective study of all horses that showed a positive response to intra‐articular anaesthesia of the STJ was performed. Details of history, clinical presentation and diagnostic findings were recorded. Radiographs of affected tarsi were evaluated and scored independently by 2 observers. Follow‐up was via a telephone questionnaire with the owner. Statistical analysis was used to assess the association between the duration and degree of lameness, the response to intra‐articular anaesthesia and radiographic findings. Response to treatment was compared with the findings from the diagnostic work‐up. Results: Ninety‐one horses were included (61 unilateral and 30 bilateral lameness). Fifty‐nine percent of horses had been lame for over 2 months. There was no association between the duration and degree of lameness, or between duration or degree of lameness, intra‐articular anaesthesia and radiographic findings. Response to treatment showed a significant positive association with less severe radiographic changes within the tarsometatarsal (TMT) joint. Follow‐up was available for 48% of cases, with 52% horses returning to the same level of exercise. Conclusions: There is no association between the duration and degree of lameness, the response to intra‐articular anaesthesia and radiographic findings in horses with OA‐STJ. However, horses that improved following treatment tended to have less marked TMT joint pathology. Potential relevance: Response to intra‐articular anaesthesia should remain the gold standard for diagnosis of OA‐STJ. Predicting which cases are likely to improve following treatment remains difficult.     

In vivo effects of meloxicam on inflammatory mediators,MMP activity and cartilage biomarkers in equine joints with acute synovitis

Reasons for performing study: Meloxicam is a commonly used nonsteroidal anti‐inflammatory drug in equine practice, but little is known about its in vivo effects on joint inflammation and cartilage turnover. Objectives: To study the effects of meloxicam on biomarkers of inflammation, matrix metalloproteinase (MMP) activity, and cartilage biomarkers in joints with experimental synovitis. Methods: In a 2‐period cross‐over study, synovitis was induced at T = 0 h in the L or R intercarpal joint of 6 horses by intraarticular injection of 0.5 ng lipopolysaccharide (LPS). Horses received once daily meloxicam (0.6 mg/kg bwt per os) or placebo starting at post injection hour (PIH) 2, and clinical evaluations as well as blood and synovial fluid (SF) sampling were performed at PIH 0, 8, 24 and 168. Synovial fluid was analysed for prostaglandin E₂, bradykinin, substance P, general MMP activity, glycosaminoglycans (GAG), CS846 epitope, type II collagen cleavage fragments (C2C) and type II collagen carboxypropeptide (CPII). Concentrations in meloxicam‐ vs. placebo‐treated joints over time were compared using a linear mixed model. Results: Lipopolysaccharide injection caused marked transient synovitis without systemic effects. Meloxicam caused a significant reduction in lameness at PIH 8 and 24 and tended to reduce effusion. In addition, meloxicam significantly suppressed SF prostaglandin E₂ and substance P release at PIH 8 and bradykinin at PIH 24 compared to placebo treatment. General MMP activity at PIH 8 and 24 was significantly lower in meloxicam‐ vs. placebo‐treated joints, as were GAG, C2C and CPII concentrations at PIH 24. Conclusions: Acute transient synovitis leads to substantial increases in SF biomarkers of inflammation, MMP activity and cartilage turnover, which can be significantly suppressed by meloxicam. Potential relevance: Early oral treatment with meloxicam ameliorates not only clinical signs and joint inflammation in acute synovitis, but may also limit inflammation‐induced cartilage catabolism.     

Cartilage-derived retinoic acid-sensitive protein in equine synovial fluid from healthy and diseased joints

Reasons for performing study: More sensitive and specific diagnostic methods for early detection of changes in the joint cartilage are needed. Cartilage‐derived retinoic acid‐sensitive protein (CD‐RAP) is a potential marker of cartilage synthesis and regeneration. This is the first study on equine CD‐RAP. Objectives: To evaluate the ability of a commercially available human sandwich ELISA assay to detect equine CD‐RAP in synovial fluid from healthy and diseased joints. Methods: Synovial fluid was collected from 28 horses with no signs of joint disease and from 5 with induced inflammatory arthritis. CD‐RAP concentrations were measured using a human CD‐RAP ELISA. Intra‐ and interassay imprecision of the assay were evaluated by multiple measurements on pools of equine synovial fluid. Assay inaccuracy was determined by linearity under dilution. Results: The assay showed moderate to large intra‐ and interassay variation when applied to equine synovial fluid. Equine CD‐RAP was detected in synovial fluid from healthy horses ranged at 8.2–52 ng/ml. Repeated arthrocentesis (after injection of isotonic saline), age, joint or gender did not significantly affect CD‐RAP concentrations. Twelve hours after intra‐articular injection of lipopolysaccharide, concentrations of CD‐RAP were significantly lower than after injection of isotonic saline and remained significantly lower until the end of the study at 144 h. Conclusion and potential relevance: The assay is suitable for longitudinal monitoring of CD‐RAP concentration in individual horses. Disease significantly influenced CD‐RAP levels. Similar to previous results obtained in man, CD‐RAP seems to be a marker of cartilage synthesis and/or regeneration in horses.     

Accuracy of ultrasound‐guided injections of thoracolumbar articular process joints in horses: A cadaveric study

Reasons for performing study: Arthrosis of the articular process joints (APJs) in the caudal thoracolumbar region of horses may cause back pain and subsequent reduced performance or lameness. Ultrasound‐guided injections of the APJs of the equine back have been described only briefly in the literature. Objectives: To evaluate factors affecting the accuracy of intra‐articular injections of the APJs in the caudal thoracolumbar region. Methods: One‐hundred‐and‐fifty‐four injections with blue dye were performed on APJs including the T14–L6 region in 12 horses subjected to euthanasia for reasons unrelated to back problems. The backs were subsequently dissected to verify the location of the injectate in relation to the APJs. Results: Twenty‐seven percent of the injections were found to be intra‐articular and a total of 77% found to be within 2 mm of the joint capsule including the intra‐articular deposits. Application of a medial approach and 18 gauge needle were significantly associated with an intra‐articular injection or deposition close to the joint capsule. Operator, APJ (location) and back number (chronological) did not significantly affect the accuracy of injection. Conclusions and potential relevance: Injection of the vertebral APJ in the thoracolumbar region using ultrasound guidance is a reliable method, as most of the injections were either in or within 2 mm of the joint. Based on the findings of this cadaver study, the medial approach is expected to be the most accurate in live horses. Further investigations are required to evaluate the diagnostic and therapeutic potential of this method in clinical practice.     

Arthrogenic lameness of the fetlock: synovial fluid markers of inflammation and cartilage turnover in relation to clinical joint pain

REASONS FOR PERFORMING THE STUDY: Joint pain is one of the most common causes of lameness in the horse but its pathogenesis is poorly understood. OBJECTIVES: To investigate which synovial fluid markers may be related to the presence of clinically detectable joint pain in the horse. METHODS: Concentrations of structural (CPII, C2C, GAG) and inflammatory markers (PGE2, LTB4, CysLTs, bradykinin and substance P) were measured in fetlock joint fluid from 22 horses in which lameness was localised to the fetlock region by perineural anaesthesia. Levels of these markers were then compared in horses that responded (n = 15) to those that did not (n = 7) to subsequent intra-articular anaesthesia (IAA). RESULTS: Of all markers analysed, only substance P levels were significantly higher (P = 0.0358) in synovial fluid of horses that showed a positive response to IAA compared to those with a negative response to IAA. Notably, while PGE2 levels were found to be elevated in all 22 lame horses compared to sound controls (P = 0.0025), they were not related to the response to IAA. CONCLUSIONS: While levels of PGE2 are elevated in synovial fluid of lame horses that respond to perineural anaesthesia, only substance P is related to joint pain as detected by the response to intra-articular anaesthesia. POTENTIAL RELEVANCE: Substance P is associated with clinically detectable joint pain in the horse. Elevated levels of PGE2 in fetlock-lame horses, regardless of their response to IAA, indicate that either this mediator does not reflect intra-articular pain or that IAA might have limitations in differentiating between intra- and peri-articular sources of pain. Either way, a negative response to IAA may not exclude intra-articular pathology.     

Analgesic and anti‐inflammatory actions of robenacoxib in acute joint inflammation in dog

Schmid, V. B., Spreng, D. E., Seewald, W., Jung, M., Lees, P., King, J. N. Analgesic and anti‐inflammatory actions of robenacoxib in acute joint inflammation in dog. J. vet. Pharmacol. Therap. 33 , 118–131. The objectives of this study were to establish dose–response and blood concentration–response relationships for robenacoxib, a novel nonsteroidal anti‐inflammatory drug with selectivity for inhibition of the cyclooxygenase (COX)‐2 isoenzyme, in a canine model of synovitis. Acute synovitis of the stifle joint was induced by intra‐articular injection of sodium urate crystals. Robenacoxib (0.25, 0.5, 1.0, 2.0 and 4.0 mg/kg), placebo and meloxicam (0.2 mg/kg) were administered subcutaneously (s.c.) 3 h after the urate crystals. Pharmacodynamic endpoints included data from forceplate analyses, clinical orthopaedic examinations and time course of inhibition of COX‐1 and COX‐2 in ex vivo whole blood assays. Blood was collected for pharmacokinetics. Robenacoxib produced dose‐related improvement in weight‐bearing, pain and swelling as assessed objectively by forceplate analysis (estimated ED₅₀ was 1.23 mg/kg for z peak force) and subjectively by clinical orthopaedic assessments. The analgesic and anti‐inflammatory effects of robenacoxib were significantly superior to placebo (0.25–4 mg/kg robenacoxib) and were non‐inferior to meloxicam (0.5–4 mg/kg robenacoxib). All dosages of robenacoxib produced significant dose‐related inhibition of COX‐2 (estimated ED₅₀ was 0.52 mg/kg) but no inhibition of COX‐1. At a dosage of 1–2 mg/kg administered s.c., robenacoxib should be at least as effective as 0.2 mg/kg of meloxicam in suppressing acute joint pain and inflammation in dogs.     

Evaluation of avocado and soybean unsaponifiable extracts for treatment of horses with experimentally induced osteoarthritis

OBJECTIVE: To evaluate the use of a combination of avocado and soybean unsaponifiable (ASU) extracts for the treatment of experimentally induced osteoarthritis in horses. ANIMALS: 16 horses. PROCEDURES: Osteoarthritis was induced via osteochondral fragmentation in 1 middle carpal joint of each horse; the other joint underwent a sham operation. Horses were randomly allocated to receive oral treatment with ASU extracts (1:2 [avocado-to-soybean] ratio mixed in 6 mL of molasses; n = 8) or molasses (6 mL) alone (placebo treatment; 8) once daily from days 0 to 70. Lameness, response to joint flexion, synovial effusion, gross and histologic joint assessments, and serum and synovial fluid biochemical data were compared between treatment groups to identify effects of treatment. RESULTS: Osteochondral fragmentation induced significant increases in various variables indicative of joint pain and disease. Treatment with ASU extracts did not have an effect on signs of pain or lameness; however, there was a significant reduction in severity of articular cartilage erosion and synovial hemorrhage (assessed grossly) and significant increase in articular cartilage glycosaminoglycan synthesis, compared with placebo-treated horses. CONCLUSIONS AND CLINICAL RELEVANCE: Although treatment with ASU extracts did not decrease clinical signs of pain in horses with experimentally induced osteoarthritis, there did appear to be a disease-modifying effect of treatment, compared with findings in placebo-treated horses. These objective data support the use of ASU extracts as a disease-modifying treatment for management of osteoarthritis in horses.     

Analgesic efficacy of intra‐articular morphine in experimentally induced radiocarpal synovitis in horses

ObjectiveTo compare the analgesic effect of intra-articular (IA) and intravenous (IV) morphine in horses with experimentally induced synovitis.AnimalsEight adult horses.Study designRandomized, observer blinded, double dummy trial with sequential crossover design.MethodsRadiocarpal synovitis was induced by IA injection of lipopolysaccharide on two occasions separated by a 3-week washout period. In one study period horses received treatment IA; morphine IA (0.05 mg kg^?1) plus saline IV and in the other study period they received treatment IV; saline IA plus morphine IV (0.05 mg kg^?1). Lameness and pain were evaluated repeatedly by two observers throughout each of the two 168-hour study periods. Pain was evaluated by use of a visual analogue scale of pain intensity (VAS) and a composite measure pain scale (CMPS). Comparison of treatments was performed by analysis of variance with repeated measurements. Significance level was set to p ≤ 0.05. Inter-observer agreement and agreement between the VAS and CMPS was assessed by use of the Bland–Altman method.ResultsIntra-articular injection of LPS elicited a marked synovitis resulting in lameness and pain. IA morphine resulted in significantly less lameness than IV morphine (p = 0.03). CMPS (p = 0.09) and VAS (p = 0.10) pain scores did not differ significantly between treatments. Inter-observer agreement of the CMPS was classified as good, but only fair for the VAS. Agreement between the two pain scales was considered fair.Conclusions and clinical relevanceAn analgesic effect of IA morphine was demonstrated by significantly reduced lameness scores. The results support the common practice of including IA morphine in a multimodal analgesic protocol after arthroscopic surgery, although further studies in clinical cases are needed. The employed CMPS had good reproducibility, and was easy to use, but may have limited sensitivity at mild intensity pain.     

Effect of Four Antimicrobial Lavage Solutions on the Tarsocrural Joint of Horses

Three concentrations of povidone-iodine (0.1% w/v, 0.2% w/v, 0.5% w/v) and one concentration of chlorhexidine (0.5% w/v) were selected as antimicrobial joint lavage solutions. Through-and-through joint lavage was performed with one of these antimicrobial solutions on a tarsocrural joint of 12 horses. The contralateral tarsocrural joints (control limbs) were lavaged with a balanced electrolyte solution (BES). The effect of the lavage solution on the joints was evaluated with respect to lameness, foot flight pattern, soreness to joint palpation, articular and periarticular enlargement, and synovial fluid composition on Day 1,4, and 8 postlavage. On Day 8 postlavage, all horses were euthanized and the tarsocrural joints were examined.
All solutions induced a synovitis. Based on clinical assessment, synovial fluid protein levels, color, clarity, mucin clot forming ability, gross appearance of the joint at necropsy, and synovial membrane histologic evaluation, a similar, mild, transient, synovitis was induced by the BES and 0.1% povidone-iodine (PI) solution. The 0.2% PI solution induced a more prolonged neutrophilic response and poorer mucin clot forming ability in the synovial fluid as compared to the BES.
The 0.5% PI and 0.5% chlorhexidine solutions produced severe lameness, soreness to joint palpation, and limb enlargement. The elevated synovial fluid total protein content persisted significantly longer (p < 0.05) than the corresponding control (BES) solution. Histologic evaluation of the synovial membrane confirmed the presence of a moderate to severe neutrophilic synovitis in these treatment groups.     

Effects of intra-articular administration of dimethylsulfoxide on chemically induced synovitis in immature horses

The effects of intra-articular administration of dimethylsulfoxide (DMSO) on chemically induced synovitis in the middle carpal joint of 6 weanling horses were evaluated. Following aseptic collection of synovial fluid, the middle carpal joint of each forelimb was injected with 50 mg of Na-monoiodoacetate to induce synovitis. Eight days after injection, synovial fluid was obtained and the right middle carpal joints were injected with 2 ml of 40% DMSO in lactated Ringer solution. The corresponding joints of the left limb (control) were injected with 2 ml of lactated Ringer solution. Sampling and treatments were repeated on post-injection days 11 and 14, for a total of 3 treatments. Horses were visually evaluated daily for lameness and joint effusion. Synovial fluid was evaluated for color and clarity, differential and total WBC count, total protein content, and hyaluronic acid concentration. The Kaegi gait analysis system provided an objective assessment of lameness prior to inducing synovitis, again on day 7, and on day 17. At necropsy (day 17), synovial fluid, synovial membrane, and articular cartilage specimens were collected. Joint effusion was evident 12 hours after injection of Na-monoiodoacetate in all joints. Mild lameness was evident at 24 hours; however, the lameness resolved by 72 hours. Objective assessment of lameness did not reveal significant differences between treatment or control limbs. Hyaluronic acid concentrations increased significantly (P = 0.023) above baseline values in most joints over the study period. Synovial fluid WBC counts increased significantly (P = 0.002) following Na-monoiodoacetate injection and remained significantly (P = 0.002) above baseline values throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Qualitative assessment of corticosteroid cervical articular facet injection in symptomatic horses

Cervical stenotic myelopathy (CSM) is the most common cause of noninfectious spinal cord ataxia in horses. Intra‐articular injection of corticosteroids into the facet joints of horses with CSM may relieve clinical signs of the disease process. However, there is a paucity of literature regarding the efficacy of facet injection therapy in horses with CSM. This retrospective study describes the return to normal function or improvement in performance of horses after ultrasound‐guided cervical facet injection that had previously shown signs of ataxia, obscure lameness or neck pain, prior to injection.     

Influence of an n‐3 long‐chain polyunsaturated fatty acid‐enriched diet on experimentally induced synovitis in horses

Dietary n‐3 long‐chain polyunsaturated fatty acid (LCPUFA) supplementation has previously been shown to modify joint‐related inflammation in several species, although information in the horse is lacking. We investigated whether dietary supplementation with n‐3 LCPUFA would modify experimentally induced synovitis in horses. Twelve, skeletally mature, non‐pregnant mares were randomly assigned to either a control diet (CONT) or an n‐3 long‐chain fatty acid‐enriched treatment diet (N3FA) containing 40 g/day of n‐3 LCPUFA for 91 days. Blood samples taken on days 0, 30, 60 and 90, and synovial fluid collected on days 0 and 90 were processed for lipid composition. On day 91, joint inflammation was stimulated using an intra‐articular (IA) injection of 100 ng of recombinant equine IL‐1beta (reIL‐1β). Synovial fluid samples taken at post‐injection hours (PIH) 0, 4, 8 and 24 were analysed for prostaglandin E₂ (PGE₂), matrix metalloproteinase (MMP) activity and routine cytology. Synovium and articular cartilage samples collected at PIH 8 were analysed for gene expression of MMP 1 and MMP 13, interleukin‐1beta (IL‐1β), cyclooxygenase 2 (COX‐2), tumour necrosis factor‐alpha and the aggrecanases, a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)‐4 and ADAMTS‐5. A 90‐day feeding period of n‐3 LCPUFA increased serum phospholipid and synovial fluid lipid compositions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) compared to CONT horses. The reIL‐1β injection caused an inflammatory response; however, there was no effect of dietary treatment on synovial fluid PGE2 content and MMP activity. Synovial tissue collected from N3FA horses exhibited lower expression of ADAMTS‐4 compared to CONT horses. Despite the presence of EPA and DHA in the synovial fluid of N3FA horses, dietary n‐3 LCPUFA supplementation did not modify synovial fluid biomarkers compared to CONT horses; however, the lower ADAMTS‐4 mRNA expression in N3FA synovium warrants further investigation of n‐3 LCPUFA as a joint therapy.     

Synovial fluid bupivacaine concentrations following single intra‐articular injection in normal and osteoarthritic canine stifles

Intra‐articular bupivacaine helps alleviate pain in animals receiving joint surgery, but its use has become controversial as ex vivo studies have illuminated the potential for chondrotoxicity. Such studies typically involve cell cultures incubated in solutions containing high bupivacaine concentrations for long durations. The aim of this study was to measure the actual synovial fluid bupivacaine concentrations after intra‐articular injection. Eight healthy beagles with normal stifles and 22 large and giant‐breed dogs with stifle osteoarthritis (OA) were treated with a single intra‐articular injection of bupivacaine (1 mg/kg) into a stifle. Joint fluid samples were taken from the treated stifle immediately after injection and 30 min after injection and analyzed for bupivacaine concentrations. Immediately after injection, the median bupivacaine concentrations in normal and OA stifles were 3.6 and 2.5 mg/mL, respectively. Thirty minutes after injection, bupivacaine concentrations in normal and OA stifles were 0.4 and 0.6 mg/mL, respectively. These results provide insight into the pharmacokinetics of bupivacaine after injection into a joint. Given its immediate dilution and rapid drop in synovial fluid concentration, bupivacaine is unlikely to damage chondrocytes when administered as a single intra‐articular injection.