Safety and Synovial Inflammatory Response After Intra-articular Injection of Botulinum Toxin Type A in Healthy Horses.

Botulinum toxin type A (BoNT-A) is a promising alternative for patients suffering from chronic joint pain. The aim of this study was to investigate whether a single injection of BoNT-A would produce adverse effects on clinical parameters and synovial parameters as well as lameness. One randomly selected radiocarpal joint was treated with 50 U of BoNT-A in eight horses, and the contralateral joint received saline solution. All horses received injections at day 0 and were re-evaluated twice daily for 7 days for heart rate (HR), respiratory rate (RR), rectal temperature (RT), mucous membrane color, capillary refill time, intestinal motility, appetite, water intake, defecation, urination, and attitude. At these same time points, joint pain and circumference were assessed. Objective lameness evaluations were performed once daily for 7 days and synovial fluid samples were collected at baseline, post-injection hour (PIH) 24 and PIH 168 and evaluated for synovial fluid parameters. HR and RT remained clinically unaltered, despite oscillations over time (P = .001). The remaining clinical parameters were unaltered by treatment or time (P > .05). Joint pain was not elicited by flexion and palpation in both limbs as well as carpal circumference was not altered (P = .88). Lameness was observed only on saline limbs. Cellular parameters evaluated in synovial fluid samples from both carpi had significantly increased from baseline to PIH 24, decreasing at PIH 168 (P < .05). It was concluded that the injection of 50 U BoNT-A is suggested to be a safe therapy for intra-articular use in horses and must be verified by further investigation.

Intra-articular Corticosteroids for Knee Pain-What Have We Learned from the Equine Athlete and Current Best Practice.

The use of intra-articular corticosteroids for traumatic arthritis and osteoarthritis (OA) is common in the horse. The beneficial and deleterious effects of the principal corticosteroids used betamethasone esters (Celestone [Soluspan], methylprednisolone acetate [Depo Medrol], and triamcinolone acetonide [TA] [Vetalog or Kenalog]) have been defined for the horse. While TA has both disease-modifying as well as symptom-modifying effects, methyl prednisolone acetate has deleterious effects on the articular cartilage. Studies in traumatically injured joints show the same rationale (suppression of deleterious mediators associated with inflammation) and positive results from the use of TA in both equine and human patients. Studies in the experimental equine OA model allow for more in-depth knowledge of disease-modifying effects. Recent insights allow us to understand posttraumatic OA as an early consequence of joint injury that may require a more aggressive and proactive treatment approach than commonly applied to date.

An investigation of mechanical nociceptive thresholds in dogs with hind limb joint pain compared to healthy control dogs.

This study investigated the effects of osteoarthritis (OA) on somatosensory processing in dogs using mechanical threshold testing. A pressure algometer was used to measure mechanical thresholds in 27 dogs with presumed hind limb osteoarthritis and 28 healthy dogs. Mechanical thresholds were measured at the stifles, radii and sternum, and were correlated with scores from an owner questionnaire and a clinical checklist, a scoring system that quantified clinical signs of osteoarthritis. The effects of age and bodyweight on mechanical thresholds were also investigated. Multiple regression models indicated that, when bodyweight was taken into account, dogs with presumed osteoarthritis had lower mechanical thresholds at the stifles than control dogs, but not at other sites. Non-parametric correlations showed that clinical checklist scores and questionnaire scores were negatively correlated with mechanical thresholds at the stifles. The results suggest that mechanical threshold testing using a pressure algometer can detect primary, and possibly secondary, hyperalgesia in dogs with presumed osteoarthritis. This suggests that the mechanical threshold testing protocol used in this study might facilitate assessment of somatosensory changes associated with disease progression or response to treatment.

The effect of intra-articular botulinum toxin A on substance P, prostaglandin E2, and tumor necrosis factor alpha in the canine osteoarthritic joint.

BACKGROUND: Recently, intra-articular botulinum toxin A (IA BoNT A) has been shown to reduce joint pain in osteoarthritic dogs. Similar results have been reported in human patients with arthritis. However, the mechanism of the antinociceptive action of IA BoNT A is currently not known. The aim of this study was to explore this mechanism of action by investigating the effect of IA BoNT A on synovial fluid (SF) and serum substance P (SP), prostaglandin E2 (PGE2), and tumor necrosis factor alpha (TNF-α) in osteoarthritic dogs. Additionally, the aim was to compare SF SP and PGE2 between osteoarthritic and non-osteoarthritic joints, and investigate associations between SP, PGE2, osteoarthritic pain, and the signalment of dogs. Thirty-five dogs with chronic naturally occurring osteoarthritis and 13 non-osteoarthritic control dogs were included in the study. Osteoarthritic dogs received either IA BoNT A (n = 19) or IA placebo (n = 16). Serum and SF samples were collected and osteoarthritic pain was evaluated before (baseline) and 2 and 8 weeks after treatment. Osteoarthritic pain was assessed with force platform, Helsinki Chronic Pain Index, and joint palpation. Synovial fluid samples were obtained from control dogs after euthanasia. The change from baseline in SP and PGE2 concentration was compared between the IA BoNT A and placebo groups. The synovial fluid SP and PGE2 concentration was compared between osteoarthritic and control joints. Associations between SP, PGE2, osteoarthritic pain, and the signalment of dogs were evaluated. RESULTS: There was no significant change from baseline in SP or PGE2 after IA BoNT A. Synovial fluid PGE2 was significantly higher in osteoarthritic compared to control joints. Synovial fluid PGE2 correlated with osteoarthritic pain. No associations were found between SP or PGE2 and the signalment of dogs. The concentration of TNF-α remained under the detection limit of the assay in all samples. CONCLUSIONS: The results suggest that the antinociceptive effect of IA BoNT A in the joint might not be related to the inhibition of SP nor PGE2. Synovial fluid PGE2, but not SP, could be a marker for chronic osteoarthritis and pain in dogs.

Widespread somatosensory sensitivity in naturally occurring canine model of osteoarthritis.

Osteoarthritis (OA)-associated pain is a leading cause of disability. Central sensitization (CS), as a result of OA, is recognized as an important facet of human patients' chronic pain and has been measured in people using quantitative sensory testing (QST) testing. The spontaneous canine OA model has been suggested as a good translational model, but CS has not been explored in this model. In this study, QST was performed on dogs with and without spontaneous hip or stifle OA to determine whether OA is associated with CS in this model. Mechanical (von Frey and blunt pressure) and thermal (hot and cold) sensory thresholds obtained in dogs with chronic OA-associated pain (n = 31) were compared with those of normal dogs (n = 23). Dogs were phenotyped and joint-pain scored, and testing was performed at the OA-affected joint, cranial tibial muscle, and dorsal metatarsal region. QST summary data were evaluated using mixed-effect models to understand the influence of OA status and covariates, and dogs with OA and control dogs were compared. The presence of OA was strongly associated with hyperalgesia across all QST modalities at the index joint, cranial tibial muscle, and metatarsal site. Mechanical QST scores were significantly moderately negatively correlated with total joint-pain scores. The spontaneous canine OA model is associated with somatosensory sensitivity, likely indicative of CS. These data further validate the canine spontaneous OA model as an appropriate model of the human OA pain condition.

Intra-articular botulinum toxin A for the treatment of osteoarthritic joint pain in dogs: a randomized, double-blinded, placebo-controlled clinical trial.

The aim of this study was to investigate the efficacy of intra-articular (IA) botulinum toxin A (IA BoNT A) for the treatment of osteoarthritic joint pain in dogs. The study was a placebo-controlled, randomized, double-blinded clinical trial with parallel group design and 12-week follow-up. Thirty-six dogs with chronic lameness due to stifle, hip or elbow osteoarthritis were randomized to receive an IA injection of 30IU of BoNT A or placebo. The main outcome variables were vertical impulse (VI) and peak vertical force (PVF) measured with a force platform, and Helsinki chronic pain index (HCPI). Subjective pain score and the need for rescue analgesics were secondary variables. The response to treatment was assessed as the change from baseline to each examination week. The variables were analyzed by ANOVA with repeated measurements and results were considered statistically significant if P ⩽ 0.05. The improvement from baseline to 12 weeks after baseline was statistically significant in VI, PVF and HCPI in the treatment group (P=0.001, P=0.054 and P=0.053, respectively). Additionally, there were statistically significant improvements in VI in the treatment group at 2, 4 and 8 weeks after baseline (P=0.037, P=0.016 and P=0.016, respectively). The difference between groups in improvement in VI was statistically significant at 12weeks after baseline (P=0.005). There was no significant change in the subjective pain score or in the requirement for rescue analgesics in either group. No major adverse events thought to be related to trial protocol were detected. These results suggest that IA BoNT A has some efficacy in reducing osteoarthritic pain in dogs.

Thermal nociception as a measure of non-steroidal anti-inflammatory drug effectiveness in broiler chickens with articular pain.

Pain associated with poultry lameness is poorly understood. The anti-nociceptive properties of two non-steroidal anti-inflammatory drugs (NSAIDs) were evaluated using threshold testing in combination with an acute inflammatory arthropathy model. Broilers were tested in six groups (n=8 per group). Each group underwent a treatment (saline, meloxicam (3 or 5mg/kg) or carprofen (15 or 25mg/kg)) and a procedure (Induced (arthropathy-induction) or sham (sham-handling)) prior to testing. Induced groups had Freund's complete adjuvant injected intra-articularly into the left intertarsal joint (hock). A ramped thermal stimulus (1°C/s) was applied to the skin of the left metatarsal. Data were analysed using random-intercept multi-level models. Saline-induced birds had a significantly higher skin temperature (± SD) than saline-sham birds (37.6 ± 0.8°C vs. 36.5 ± 0.5°C; Z=-3.47, P<0.001), consistent with an inflammatory response. Saline was associated with significantly lower thermal thresholds (TT) than analgesic treatment (meloxicam: Z=2.72, P=0.007; carprofen: Z=2.58, P=0.010) in induced birds. Saline-induced birds also had significantly lower TT than saline-sham birds (Z=-2.17, P=0.030). This study found direct evidence of an association between inflammatory arthropathies and thermal hyperalgesia, and showed that NSAID treatment maintained baseline thermal sensitivity (via anti-nociception). Quantification of nociceptive responsiveness in a predictable broiler pain model identified thermal anti-hyperalgesic properties of two NSAIDs, which suggested that therapeutically effective treatment was provided at the doses administered. Such validation of analgesic strategies will increase the understanding of pain associated with specific natural broiler lameness types.

[Use of gold implants as a treatment of pain related to canine hip dysplasia--a review. Part 2: Clinical trials and case reports]. / Anwendung von Goldimplantaten zur Schmerztherapie bei kaniner Hüftgelenkdysplasie--eine Literaturübersicht. Teil 2: Klinische Studien und Fallberichte.

Gold bead implantation/gold acupuncture is becoming increasingly used in veterinary medicine as a method of pain treatment in cases of osteoarthritic diseases. Part one of the overview dealing with the use of gold implants as a treatment of canine hip joint dysplasia (cHD) introduced the method of implanting gold in tissue and publications which investigated the subsequent effects of implantation. This article focuses on publications concerning the clinical effectiveness of gold implantation within the scope of pain therapy in cHD. Due to the study design, a classification using evidence-based levels (EbL) was carried out. Three double-blind, placebo-controlled randomised studies (EbL II) were considered together with three retrospective studies on own patients (EbL IV) and five case studies (EbL IV). While the case and retrospective studies reported impressive therapeutic success in treating cHD-incurred pain with gold implantation, a pain-reducing effect through gold implantation was only demonstrated in one of the three double-blind studies. The two remaining EbL II studies found no differences between the placebo-group and the group of dogs treated with gold implantation. In one of these two studies, kinematic and kinetic gait analyses were used for objective evaluation of the effects of the treatment. Thus, the only study that carried out an objective evaluation of the therapeutic result of gold implantation came to the conclusion that the method is ineffective. For a concluding assessment of gold implantation in the case of cHD, gait analysis studies investigating the effects of gold implantation in comparison to a standard treatment with nonsteroidal anti-inflammatory drugs are currently lacking.

Scintigraphic assessment of the metacarpophalangeal and metatarsophalangeal joints of horses with joint pain.

Our aims were to evaluate the pattern of radiopharmaceutical uptake in horses with lameness related to the metacarpophalangeal and/or metatarsophalangeal joint and compare the results with similar information from sound horses. It was hypothesized bthat there would be a difference in radiopharmaceutical uptake between the lame and contralateral limb in unilaterally lame horses and that there would be a difference between lame and sound horses. Nuclear scintigraphic images of 43 horses with forelimb lameness and 30 horses with hindlimb lameness were evaluated. In all horses lameness was improved by intraarticular analgesia of the joint, or by perineural analgesia of the palmar/plantar (at the junction of the proximal 3/4 and the distal 1/4 of the metacarpal/metatarsal regions) and palmar/plantar metacarpal/metatarsal nerves. All images were assessed subjectively and a quantitative image analysis was performed by drawing a vertical line profile through the center of each joint in the lateral images and using region of interest analysis in both lateral and dorsal/plantar images. Ratios of radiopharmaceutical uptake were compared for each region between lame and contralateral limbs in unilaterally lame horses and between lame and control horses. There was a significant difference in the ratio of radiopharmaceutical uptake in the proximal aspect of the proximal phalanx between lame and nonlame forelimbs in unilaterally lame horses and in both lame and contralateral limbs of lame horses compared with control horses for the regions of the distal aspect of the third metacarpal/metatarsal bone and the proximal sesamoid bones. However, the profile analysis was of limited clinical value.

Structural and biomechanical aspects of equine sacroiliac joint function and their relationship to clinical disease.

Pain originating from the sacroiliac joint (SIJ) in horses has long been associated with poor performance, yet specific diagnosis of sacroiliac dysfunction (SID) has been difficult to achieve. Clinical presentation of SID appears to fall into two categories. The first, presenting as pain and poor performance, is responsive to local analgesia of periarticular structures with poorly defined pathology. The second presents primarily as poor performance with bony pathological changes as a result of chronic instability. Diagnostic tests based on biomechanics as well as manual provocation for SIJ pain have formed the basis of tests currently used to diagnose SIJ dysfunction in humans. This review summarises the anatomy and biomechanics of the equine SIJ and current biomechanical, innervation and motor control concepts in human SID. The relationship between abnormal SIJ motion and altered neuromotor control with clinical disease of the equine SIJ are discussed. Future utilisation of these principles to develop new diagnostic and management tools for the equine SID is promising.

Alteration of distal tarsal subchondral bone thickness pattern in horses with tarsal pain.

REASONS FOR PERFORMING STUDY: Understanding of the development of pathology and source of pain in distal tarsal osteoarthritis is poorly understood. Magnetic resonance imaging is often used in the analysis of human osteoarthritis (OA) because it is sensitive to early changes. HYPOTHESIS: In association with distal tarsal joint (DTJ) pain, there will be an alteration in the characteristic subchondral bone (SCB) thickness pattern of horses with no history of pain when subjected to low-level exercise. METHODS: Sixteen cadaver tarsal joints were collected from 9 mature horses with a history of tarsal pain and radiographic evidence of OA; 3 cadaver tarsi were collected from 2 mature horses with a history of tarsal pain and no radiographic abnormality. Magnetic resonance images were acquired using high-resolution sagittal 3D T1 weighted spoiled gradient echo sequence. Subchondral bone thickness was measured on sagittal images at dorsal and plantar locations on the proximal and distal aspects of the central (CT) and third (T3) tarsal bones and proximal aspect of the third metatarsal bone (MT3). RESULTS: In tarsi with radiographic evidence of OA medial and lateral SCB thicknesses were greater than midline on the proximal and distal aspects of CT and T3. Lateral SCB thickness was greater than medial on the proximal aspect of MT3. There was an increase in SCB thickness at the majority of sites compared with normal horses. There were too few joints in the group without radiographic changes to analyse statistically. In painful tarsi SCB thickness was greater medially than laterally at all sites. In horses without tarsal pain all lateral sites had greater SCB thickness, except the proximal aspect of CT. CONCLUSIONS: There is alteration of normal SCB thickness patterns in painful tarsi. Different thickness patterns could represent different types of pathological processes. POTENTIAL CLINICAL RELEVANCE: Further work is required to elucidate the pathological processes leading to OA of the DTJs.

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.

Glenoid dysplasia and bicipital tenosynovitis in a Maine coon cat.

This report describes a rare case of bicipital tenosynovitis in a Maine coon cat. The cat, a three-and-half-year-old neutered female, presented with chronic weightbearing lameness of the left forelimb. Flexion of the left glenohumeral joint and extension of the left cubital joint were resented, and palpation of the biceps brachii tendon in the bicipital groove elicited pain. A mild incongruity of the joint with mild degenerative changes was seen radiographically. Glenohumeral joint dysplasia was suspected. Ultrasound examination revealed marked thickening of the bicipital tendon and moderate effusion of the left bicipital tendon sheath. Positive contrast radiography of the joint confirmed dilation of the tendon sheath. A tentative diagnosis of bicipital tenosynovitis was made and confirmed on arthrotomy. Surgical removal of osteophytes resulted in the cat being free from pain but a mild lameness recurred six months after surgery.

Effect of anaesthesia of the palmar digital nerves on proximal interphalangeal joint pain in the horse.

REASONS FOR PERFORMING STUDY: Anaesthesia of the palmar digital nerves is claimed to attenuate lameness in some horses that are lame because of pain in the proximal interphalangeal (PIP) joint. OBJECTIVE: To determine the response of horses with pain in the PIP joint to anaesthesia of the palmar digital nerves. METHODS: Horses were video recorded trotting before and after induction of pain in the PIP joint and 10 mins after anaesthesia of the palmar digital nerves. The palmar digital nerves were anaesthetised 3 times at different sites, and the video recorded gaits were scored subjectively. RESULTS: The median lameness score of gaits after administration of 2% mepivacaine 1 cm proximal to the cartilages of the foot was not significantly different from the median lameness score before anaesthesia of the palmar digital nerves (P > or = 0.05), although that of 1 of 6 horses improved markedly. The median lameness score was significantly (P < or = 0.05) improved after mepivacaine was administered 2 and 3 cm proximal to the cartilages of the foot. CONCLUSIONS: The PIP joint is unlikely to be anaesthetised when the palmar digital nerves are anaesthetised at the proximal margin of the cartilages of the foot. POTENTIAL RELEVANCE: Pain within the PIP joint cannot be excluded as a cause of lameness when lameness is attenuated by anaesthesia of the palmar digital nerves at any site proximal to the proximal margin of the cartilages of the foot.

Treatment methods for pain in the osteoarthritic patient.

Osteoarthritis is one of the most common clinical problems for which pet owners seek veterinary consultation. Proper management of osteoarthritis is rewarding to the patient, client, and veterinarian alike. The foundation for treatment of osteoarthritis is weight control, exercise moderation, and administration of anti-inflammatory agents. This section of the text addresses clinically important mechanisms of osteoarthritis and the use of anti-inflammatory agents targeted to reduce pain and inflammation associated with the disease.