Placebo-controlled pilot study of the effects of an eggshell membrane-based supplement on mobility and serum biomarkers in dogs with osteoarthritis.

Osteoarthritis (OA) is a debilitating disease in dogs. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat OA; however, many dogs do not obtain adequate pain relief with an NSAID alone. This pilot study evaluated the systemic anti-inflammatory and mobility enhancing effects of an eggshell membrane-based nutritional supplement in dogs with OA-associated pain and mobility impairment. Twenty-seven dogs with OA-associated pain were enrolled into a randomized, double-masked, placebo-controlled, proof of principle pilot study and received either placebo or an eggshell membrane-based nutritional supplement over a 12-week period. Inflammatory biomarkers (IL-2, IL-6, IL-8, tumor necrosis factor-α, C-reactive protein, S100A12, and N-methylhistamine) were measured at Day 0 and Day 84. Owner questionnaires (CBPI and LOAD) were completed at Day 0, Day 42, and Day 84. Differences between groups over time were calculated. Twenty-two dogs completed the pilot study. Inflammatory biomarker IL-2 decreased in the supplement group, compared to the placebo group. Although small, the difference was statistically significant at an alpha of 0.1 (P=0.069). LOAD scores were numerically lower in the supplement group, but not significantly different from the placebo group at Day 0. Day 84 LOAD scores were significantly lower in the supplement group compared to the placebo group (P=0.034). CBPI results did not show the same pattern. The changes in biomarkers and LOAD scores were small, and do not provide definitive evidence of positive effects. However, these pilot results provide a rationale for performing a larger placebo-controlled study of the potential effects of the eggshell membrane-based nutritional supplement.

Measurement of chronic pain in companion animals: Discussions from the Pain in Animals Workshop (PAW) 2017.

In the face of increasing recognition and interest in treating chronic pain in companion animals, we struggle with a lack of therapeutic options. A significant barrier to the development of new therapeutics, or the critical evaluation of current therapies, is our inability to accurately measure chronic pain and its impact on companion animals. Over the last 20 years, much progress has been made in developing methods to measure chronic pain via subjective and objective methods - particularly in owner assessment tools and measurements of limb use and activity. Most work has been focused on chronic joint pain conditions, but there has been relatively little work in other areas of chronic pain, such as neuropathic and cancer pain. Although progress has been made, there is a considerable interest in improving our assessment of chronic pain, as evidenced by the multiple disciplines across industry, academia, and clinical practice from the veterinary and human medical fields that participated in the Pain in Animals Workshop held at the National Institutes of Health in 2017. This review is one product of that meeting and summarizes the current state of knowledge surrounding the measurement of chronic pain (musculoskeletal, cancer, neuropathic), and its impact, in cats and dogs.

Association of Canine Osteosarcoma and Monocyte Phenotype and Chemotactic Function.

BACKGROUND: Monocytes/macrophages are likely key cells in immune modulation in dogs with osteosarcoma (OSA). Increased peripheral monocyte counts are negatively correlated with shorter disease-free intervals in dogs with OSA. Understanding the monocyte/macrophage's modulatory role in dogs with OSA can direct further studies in immunotherapy development for OSA. HYPOTHESIS/OBJECTIVES: That OSA evades the immune response by down-regulating monocyte chemokine receptor expression and migratory function, and suppresses host immune responses. ANIMALS: Eighteen dogs with OSA that have not received definitive treatment and 14 healthy age-matched controls METHODS: Clinical study-expression of peripheral blood monocyte cell surface receptors, monocyte mRNA expression and cytokine secretion, monocyte chemotaxis, and survival were compared between clinical dogs with OSA and healthy control dogs. RESULTS: Cell surface expression of multiple chemokine receptors is significantly down-regulated in peripheral blood monocytes of dogs with OSA. The percentage expression of CCR2 (median 58%, range 2-94%) and CXCR2 expression (median 54%, range 2-92%) was higher in control dogs compared to dogs with OSA (CCR2 median 29%, range 3-45%, P = 0.0006; CXCR2 median 23%, range 0.2-52%, P = 0.0007). Prostaglandin E2 (PGE2 ) (OSA, median 347.36 pg/mL, range 103.4-1268.5; control, 136.23 pg/mL, range 69.93-542.6, P = .04) and tumor necrosis factor-alpha (TNF-α) (P = .02) levels are increased in OSA monocyte culture supernatants compared to controls. Peripheral blood monocytes of dogs with OSA exhibit decreased chemotactic function when compared to control dogs (OSA, median 1.2 directed to random migration, range 0.8-1.25; control, 1.6, range of 0.9-1.8, P = .018). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with OSA have decreased monocyte chemokine receptor expression and monocyte chemotaxis, potential mechanisms by which OSA might evade the immune response. Reversal of monocyte dysfunction using immunotherapy could improve survival in dogs with OSA.

Initial evaluation of a canine stifle arthrotomy post-operative pain model.

Most models of acute post-operative orthopedic pain involve the injection of a clinically irrelevant pro-inflammatory agent. The ideal model should, however, be clinically relevant and allow full functional recovery of enrolled animals after research is completed. This study explored the validity of a model employing arthrotomy and objectively measured limb use. Six purpose-bred Beagles underwent arthrotomies on each stifle with a washout period in between. Using a randomized crossover design, each dog received placebo and an extended-release buprenorphine (ER-Bup) preparation. Static and dynamic ground reaction forces (GRFs) were measured prior to and for 72 h following surgery using a pressure sensitive walkway (PSW). GRFs for each hind limb were compared using difference (delta), and symmetry indices (SI). The effects of surgery and of treatment were analyzed using repeated measures ANCOVA. The results indicated significantly decreased limb use compared to baseline for placebo, and significantly increased limb use in the ER-Bup group over placebo at all times for % bodyweight distribution (%BWdistrib), peak vertical force (PVF) and vertical impulse (VI). There was a significant treatment by time interaction for velocity (P = 0.03) and %BWdistrib (P = 0.01, 0.003). Overall, the data show that reduced limb use was present for at least 72 h following arthrotomy. In addition, the use of the ER-Bup analgesic decreased lameness, confirming the validity of this approach as a model of post-operative pain. Subjective assessments did not detect the pain-inducing effects of arthrotomy or pain-alleviating effects of treatment, and subjective measures of procedural pain in research dogs need to be developed.

Revision of a loose cementless short-stem threaded femoral component using a standard cementless stem in a canine hip arthroplasty.

A Helica short-stemmed femoral prosthesis that was identified as being loose one year after implantation was revised with a standard long stem cementless BFX femoral prosthesis. A double pelvic osteotomy was also performed to improve the orientation of the stable acetabular cup. Despite complete resorption of the femoral neck, and a large perforation of the lateral femoral cortex, the revision stem did not subside or rotate. The prosthetic joint did not dislocate. At re-evaluation two years after revision surgery, the prosthetic components were stable. Signs of bone ingrowth into the stem and cup were evident on radiographs. The dog had a seven percent greater thigh muscle girth in the limb implanted with the hip prosthesis compared to the contralateral limb, and was very active with no lameness.

Surgical treatment of right-sided renal lymphoma with invasion of the caudal vena cava.

An eight-year-old, male castrated basset hound presenting with a three-month history of lethargy was examined. Diagnostic tests including radiography and ultrasonography showed a right-sided renal mass. A 99mTc diethylenetriamine penta-acetic acid scan demonstrated that this kidney was non-functional. At surgery, invasion of the caudal vena cava was found, and the renal segment of the vena cava and the right kidney were resected. The left renal vein was anastomosed to the more proximal vena cava using a polytetrafluoroethylene graft, and the dog recovered well. Two days postsurgery, the dog suffered an acute episode of aspiration pneumonia and was euthanased. The renal mass was diagnosed as lymphoma on histopathology.

Central sensitization as a result of surgical pain: investigation of the pre-emptive value of pethidine for ovariohysterectomy in the rat.

The development of central hypersensitivity as a result of a routine surgical procedure, midline ovariohysterectomy, was investigated in rats using the paw pressure test (PPT) and tail-flick latency (TFL) tests of spinal reflex activity. In addition, the modulating effect of pre-emptive versus post-operative administration of pethidine (a short-acting pure mu-opioid agonist) on the development of central hypersensitivity was studied. Initial experiments indicated that pethidine (15 mg/kg, i.m.) gave sub-maximal increases in thresholds for 60 min, and also that the administration of an anaesthetic did not unduly prolong the action of pethidine. Subsequently, 24 female Wistar rats were allocated to 1 of 4 treatment protocols: (1) anaesthesia without analgesics; (2) anaesthesia and surgery (midline ovariohysterectomy) without analgesics; (3) anaesthesia and surgery with pre-operative administration of pethidine; (4) anaesthesia and surgery with post-operative administration of pethidine. Thirty-five minutes after the end of anaesthesia thermal and mechanical nociceptive thresholds were measured at stepwise increasing intervals for 480 min. Changes were expressed as percentage changes from baseline (PPT) or deviation from expected values (TFL). Area under the threshold versus time response curves (AUCs) were also calculated for the following time sectors: 30-90, 90-150, 150-270, 270-390 and 390-510 min post-anaesthetic. Results of the TFL testing did not indicate the development of any significant hyperalgesia in any groups, but the results of the PPT did. In the time sectors 150-270 and 270-390 min post-anaesthetic, the AUCs in rats subjected to anaesthesia and surgery with either post-operative administration of pethidine or surgery with no analgesic drug administration, were significantly lower than the AUCs in rats given analgesics pre-operatively or those subjected to general anaesthesia alone (P < 0.01), Mann-Whitney). In summary, it appears that pethidine, in this protocol, prevented the development of surgically induced hyperalgesia when it was given pre-emptively.