Effects of a Bio-Electromagnetic Energy Regulation Blanket on Thoracolumbar Epaxial Muscle Pain in Horses.

Back pain and inflammation of the epaxial musculature is a significant problem in all equine athletes. Treatment of back pain can be challenging and often requires a multimodal approach. In humans, bio-electromagnetic energy regulation therapy (BEMER) has been reported to be effective in pain modulation. With its increased use in people comes a similar robust application in veterinary medicine unfortunately, there is unsubstantiated evidence for this type of therapy in horses. Objectives of this study were to assess analgesic responses and biomechanical outcome variables using a bio-electromagnetic energy regulation therapy blanket, and to evaluate serum biomarkers as a method to monitor the treatment effects in horses with thoracolumbar epaxial muscle pain. Cohort study of 8 horses treated for 3 consecutive days. Horses with naturally-occurring thoracolumbar epaxial muscle pain were used in this study. Objective outcome variables were recorded daily for 5 days, which included spinal evaluation, mechanical nociceptive thresholds, electromyography, kinematics, kinetics, and serum biomarkers. BEMER blanket therapy significantly improved thoracolumbar epaxial muscle nociceptive thresholds. Center of pressure displacement as a measure of postural stability was significantly improved as well as significant gains in spinal flexibility were demonstrated at study completion. A significant treatment effect was not appreciated in measures of muscle tone, ground reaction forces or serum biomarkers. Limitations include the lack of a control group and a definitive structural diagnosis of thoracolumbar epaxial muscle pain. The BEMER blanket produced significant clinical and biomechanical effects in horses with back pain.

Effects of Low-Level Laser Therapy and Chiropractic Care on Back Pain in Quarter Horses.

Low-level laser therapy has been used clinically to treat musculoskeletal pain; however, there is limited evidence available to support its use in treating back pain in horses. The objective of this study was to evaluate the clinical effectiveness of low-level laser therapy and chiropractic care in treating thoracolumbar pain in competitive western performance horses. The subjects included 61 Quarter Horses actively involved in national western performance competitions judged to have back pain. A randomized, clinical trial was conducted by assigning affected horses to either laser therapy, chiropractic, or combined laser and chiropractic treatment groups. Outcome parameters included a visual analog scale (VAS) of perceived back pain and dysfunction and detailed spinal examinations evaluating pain, muscle tone, and stiffness. Mechanical nociceptive thresholds were measured along the dorsal trunk and values were compared before and after treatment. Repeated measures with post-hoc analysis were used to assess treatment group differences. Low-level laser therapy, as applied in this study, produced significant reductions in back pain, epaxial muscle hypertonicity, and trunk stiffness. Combined laser therapy and chiropractic care produced similar reductions, with additional significant decreases in the severity of epaxial muscle hypertonicity and trunk stiffness. Chiropractic treatment by itself did not produce any significant changes in back pain, muscle hypertonicity, or trunk stiffness; however, there were improvements in trunk and pelvic flexion reflexes. The combination of laser therapy and chiropractic care seemed to provide additive effects in treating back pain and trunk stiffness that were not present with chiropractic treatment alone. The results of this study support the concept that a multimodal approach of laser therapy and chiropractic care is beneficial in treating back pain in horses involved in active competition.

Efficacy of intravenous administration of hyaluronan, sodium chondroitin sulfate, and N-acetyl-d-glucosamine for prevention or treatment of osteoarthritis in horses.

OBJECTIVE To evaluate the efficacy of IV administration of a product containing hyaluronan, sodium chondroitin sulfate, and N-acetyl-d-glucosamine for prevention or treatment of osteoarthritis in horses. ANIMALS 32 healthy 2- to 5-year-old horses. PROCEDURES The study involved 2 portions. To evaluate prophylactic efficacy of the test product, horses received 5 mL of the product (n = 8) or saline (0.9% NaCl) solution (8; placebo) IV every fifth day, starting on day 0 (when osteoarthritis was induced in the middle carpal joint of 1 forelimb) and ending on day 70. To evaluate treatment efficacy, horses received either the product or placebo (n = 8/treatment) on days 16, 23, 30, 37, and 44 after osteoarthritis induction. Clinical, diagnostic imaging, synovial fluid, gross anatomic, and histologic evaluations and other tests were performed. Results of each study portion were compared between treatment groups. RESULTS Limb flexion and radiographic findings were significantly worse for horses that received the test product in the prophylactic efficacy portion than for placebo-treated horses or product-treated horses in the treatment efficacy portion. In the prophylactic efficacy portion, significantly less articular cartilage erosion was identified in product-treated versus placebo-treated horses. In the treatment efficacy portion, joints of product-treated horses had a greater degree of bone edema identified via MRI than did joints of placebo-treated horses but fewer microscopic articular cartilage abnormalities. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that caution should be used when administering the evaluated product IV to horses, particularly when administering it prophylactically, as it may have no benefit or may even cause harm.

Evaluation of intramuscularly administered sodium pentosan polysulfate for treatment of experimentally induced osteoarthritis in horses.

OBJECTIVE: To assess clinical, radiographic, histologic, and biochemical effects of sodium pentosan polysulfate (NaPPS) administered IM for treatment of experimentally induced osteoarthritis in horses. ANIMALS: 18 horses. PROCEDURES: Osteoarthritis was induced arthroscopically in 1 middle carpal joint of all horses. Nine horses received NaPPS (3 mg/kg, IM) on study days 15, 22, 29, and 36. Nine control horses received the same volume of saline (0.9% NaCl) solution IM on study days 15, 22, 29, and 36. Clinical, radiographic, gross, histologic, histochemical, and biochemical findings as well as findings of synovial fluid analysis were evaluated. RESULTS: No adverse treatment-related events were detected. Induced osteoarthritis caused a substantial increase in lameness, response to flexion, joint effusion, radiographic findings, synovial membrane inflammation, and articular cartilage fibrillation. Articular cartilage fibrillation was substantially reduced by NaPPS treatment, and concentrations of chondroitin sulfate 846 epitope were significantly increased in the synovial fluid of osteoarthritic and non-osteoarthritic joints of treated horses. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that NaPPS has some beneficial disease-modifying effects and may be a therapeutic option for osteoarthritis in horses.

Controlled delivery of transforming growth factor ß1 by self-assembling peptide hydrogels induces chondrogenesis of bone marrow stromal cells and modulates Smad2/3 signaling.

Self-assembling peptide hydrogels were modified to deliver transforming growth factor ß1 (TGF-ß1) to encapsulated bone-marrow-derived stromal cells (BMSCs) for cartilage tissue engineering applications using two different approaches: (i) biotin-streptavidin tethering; (ii) adsorption to the peptide scaffold. Initial studies to determine the duration of TGF-ß1 medium supplementation necessary to stimulate chondrogenesis showed that 4 days of transient soluble TGF-ß1 to newborn bovine BMSCs resulted in 10-fold higher proteoglycan accumulation than TGF-ß1-free culture after 3 weeks. Subsequently, BMSC-seeded peptide hydrogels with either tethered TGF-ß1 (Teth-TGF) or adsorbed TGF-ß1 (Ads-TGF) were cultured in the TGF-ß1-free medium, and chondrogenesis was compared to that for BMSCs encapsulated in unmodified peptide hydrogels, both with and without soluble TGF-ß1 medium supplementation. Ads-TGF peptide hydrogels stimulated chondrogenesis of BMSCs as demonstrated by cell proliferation and cartilage-like extracellular matrix accumulation, whereas Teth-TGF did not stimulate chondrogenesis. In parallel experiments, TGF-ß1 adsorbed to agarose hydrogels stimulated comparable chondrogenesis. Full-length aggrecan was produced by BMSCs in response to Ads-TGF in both peptide and agarose hydrogels, whereas medium-delivered TGF-ß1 stimulated catabolic aggrecan cleavage product formation in agarose but not peptide scaffolds. Smad2/3 was transiently phosphorylated in response to Ads-TGF but not Teth-TGF, whereas medium-delivered TGF-ß1 produced sustained signaling, suggesting that dose and signal duration are potentially important for minimizing aggrecan cleavage product formation. Robustness of this technology for use in multiple species and ages was demonstrated by effective chondrogenic stimulation of adult equine BMSCs, an important translational model used before the initiation of human clinical studies.

Osteoblastic differentiation of human and equine adult bone marrow-derived mesenchymal stem cells when BMP-2 or BMP-7 homodimer genetic modification is compared to BMP-2/7 heterodimer genetic modification in the presence and absence of dexamethasone.

Bone marrow-derived mesenchymal stem cells (BMDMSCs) have been targeted for use in enhancement of bone healing; and their osteogenic potential may be further augmented by genes encoding bone morphogenetic proteins (BMP's). The purpose of this study was to compare the effect of genetic modification of human and equine BMDMSCs with BMP-2 or -7 or BMP-2 and -7 on their osteoblastogenic differentiation in the presence or absence of dexamethasone. The BMDMSCs were harvested from the iliac crest of three human donors and tuber coxae of three equine donors. Monolayer cells were genetically modified using adenovirus vectors encoding BMP-2, -7 or both and cultured in the presence or absence of dexamethasone. Expression of BMPs was confirmed by enzyme linked immunosorbent assay (ELISA). To evaluate osteoblastic differentiation, cellular morphology was assessed every other day and expression and secretion of alkaline phosphatase (ALP), as well as expression levels of osteonectin (OSTN), osteocalcin (OCN), and runt-related transcription factor-2 (Runx2) were measured for up to 14 days. Human and equine BMDMSCs showed a capacity for osteogenic differentiation regardless of genetic modification or dexamethasone supplementation. Dexamethasone supplementation was more important for osteoblastogenic differentiation of equine BMDMSCs than human BMDMSCs. Genetic modification of BMDMSCs increased ALP secretion with AdBMP-2 homodimer having the greatest effect in both human and equine cells compared to AdBMP 7 or AdBMP 2/7. BMP protein elution rates reached their maximal concentration between day 4 and 8 and remained relatively stable thereafter, suggesting that genetically modified BMDMSCs could be useful for cell-based delivery of BMPs to a site of bone formation.

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.