The effect of low dose intra-articular S(+) ketamine on osteoarthritis in rats: an experimental study.

BACKGROUND: This study aimed to investigate the analgesic impact of S(+)-ketamine on pain behavior and synovial inflammation in an osteoarthritis (OA) model. METHODS: Animals were grouped as follows: OA-Saline (n = 24) and OA-Ketamine (n = 24), OA induced via intra-articular sodium monoiodoacetate (MIA); a Non-OA group (n = 24) served as the control. On the 7th day post OA induction, animals received either saline or S(+)-ketamine (0.5 mg.kg-1). Behavioral and histopathological assessments were conducted up to day 28. RESULTS: S(+)-ketamine reduced allodynia from day 7 to 28 and hyperalgesia from day 10 to 28. It notably alleviated weight distribution deficits from day 10 until the end of the study. Significant walking improvement was observed on day 14 in S(+)-ketamine-treated rats. Starting on day 14, OA groups showed grip force decline, which was countered by S(+)-ketamine on day 21. However, S(+)-ketamine did not diminish synovial inflammation. CONCLUSION: Low Intra-articular (IA) doses of S(+)-ketamine reduced MIA-induced OA pain but did not reverse synovial histopathological changes. IRB APPROVAL NUMBER: 23115 012030/2009-05.

Effect of Dioscorea villosa extract and the phytoestrogen diosgenin on ovariectomized mice with zymosan-induced arthritis

Abstract Humans are exposed to natural compounds such as phytoestrogens primarily through diet and supplements. These compounds promote health by alleviating the symptoms and illnesses associated with menopause and arthritis. Diosgenin (DSG) occurs naturally in plants such as Dioscorea villosa (DV) and binds to estrogen receptors, so it may have similar effects to this hormone, including against arthritis. Thus, we investigated the effect of chronic treatment with dry extract of DV and its phytoestrogen DSG on ovariectomized mice with arthritis. We found that dry extract of Dioscorea villosa (DV) contains the phytoestrogen diosgenin (DSG) in its composition. Furthermore, arthritic mice treated with DV and DSG showed reduced neutrophil accumulation in the articular cartilage. Also, the dry extract of DV administered orally (v.o) did not alter the leukocyte count in the joints or promote changes in the reproductive tract. However, DSG altered these parameters, with possible beneficial effects by reducing symptoms related to reproductive aging. Thus, oral treatment with dry extract of DV and subcutaneous (s.c) treatment with DSG showed promise by acting against inflammation caused by arthritis and reducing symptoms in the reproductive tract due to menopause.

Inflammatory and degenerative effects of induced osteoarthritis/rheumatoid arthritis models on temporomandibular joint of rats.

OBJECTIVE: The present study compared three models of induction of osteoarthritis (OA) and rheumatoid arthritis (RA) in the temporomandibular joint (TMJ) of rats. DESIGN: The induction method was by injection of complete Freund's adjuvant (CFA) + type II bovine collagen (CII). Twenty-four adult male rats were divided into four groups (n = 6): G1: Sham, 50 µL of 0.9% sodium chloride at the base of the tail and in each TMJ; G2: OA, 50 µL CFA+CII in each TMJ; G3: RA+OA, 100 µL of CFA+CII at the base of the tail and 50 µL CFA+CII in each TMJ; G4: RA, 100 µL of CFA+CII at the base of the tail. All injections were repeated 5 days later. Twenty-three days after the first injection, the animals were sacrificed and the TMJs were submitted to histomorphometric analysis and measurement of cytokines. The Kruskal-Wallis and Dunn tests were used (alpha=0.05). RESULTS: The total thickness of the condylar cartilage increased in G2 in relation to the other groups, G3 and G4 reduced in relation to G1; and G2 and G4 reduced in relation to G2 and G3. The levels of IL-1ß, IL-6 and TNF-α increased in the three induction models compared to G1. The level of IL-10 increased in G2 compared to the other groups and reduced in G3 and G4 compared to G1. CONCLUSION: CFA+CII induced inflammation and degeneration compatible with RA (advanced chronic stage) when injected in the tail, and compatible with OA (acute stage or early disease) when injected only in the TMJ.

Use of cannabis in the treatment of animals: a systematic review of randomized clinical trials.

Cannabis is used in the treatment of several human conditions; however, its use is still less explored in veterinary medicine. This systematic review aims to summarize the evidence of efficacy and safety of the use of cannabis for the treatment of animal disease. A literature search was performed for studies published until 16 March 2021 in five databases. Randomized clinical trials (RCTs) that reported the efficacy or safety of cannabis in the treatment of animal disease were included. The RoB 2 Tool was used to assess the risk of bias. A total of 2427 records were identified, of which six studies fully met the eligibility criteria. RCTs were conducted in dogs with osteoarthritis (n = 4), with epilepsy (n = 1), and with behavioral disorders (n = 1). All studies used cannabidiol (CBD) oil in monotherapy or in combination with other drugs. Studies used CBD at 2 or 2.5 mg kg-1 twice daily (n = 4), orally (n = 5), during 4 or 6 weeks (n = 3), and compared CBD with placebo (n = 5). CBD significantly reduced pain and increased activity in dogs with osteoarthritis (n = 3). Moreover, CBD significantly reduced the frequency of seizures in dogs with epilepsy (n = 1) and the aggressive behavior of dogs (n = 1). Although promising results were identified, studies were heterogeneous and presented risks of bias that required caution in the interpretation of findings. Therefore, there was some evidence to support the use of CBD in dogs with osteoarthritis to reduce pain and increased activity, but limited evidence against epilepsy and behavioral problems. In addition, CBD was well tolerated with mild adverse effects. More RCTs with high quality of evidence are needed, including greater numbers of animal subjects, additional species, and clear readout measures to confirm these findings.

Intra-articular ozone slows down the process of degeneration of articular cartilage in the knees of rats with osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a joint disease of multifactorial etiology, affecting mainly the knees. We aimed to evaluate the effects of two different doses of gaseous ozone intra-articularly on the knee cartilage morphology of rats with osteoarthritis (OA). METHODS: The articular lesion was induced by sodium monoiodoacetate (MIA). 40 Wistar rats were divided into 4 groups: G1 control (without lesion and without treatment), G2 articular lesion (AL) (only lesion MIA-induced), G3 AL + treatment with 5 µg/mL of ozone intra-articular, and G4 AL + treatment with 10 µg/mL of ozone intra-articular. The experiment was carried out for 60 days. RESULTS: Both doses of ozone intra-articular demonstrated less reduction in joint space (G3 and G4) compared to the G2, formation of osteophytes, but without subchondral sclerosis. Ozone decreased the volumetric density of the articular lesion (VV(AL)) of tibial. The treatments recovered VV(AL) of the femur similar to G1. Ozone lower dose (G3) showed lower tibia and femur macroscopic scores. CONCLUSION: Intra-articular gaseous ozone can delay the degeneration of articular cartilage and can represents an integrative therapy in the OA treatment of knee after 60 days of treatment. For the first time the role of ozone in articular cartilage degeneration was evaluated helping to understand this therapy.

Use of hyaluronic acid associated with triamcinolone acetonide or ozone gas in the treatment of induced osteoarthritis in rabbits.

PURPOSE: To evaluate the effects of the intra-articular application of hyaluronic acid associated with triamcinolone acetonide, and ozone gas in the treatment of induced osteoarthritis in rabbit's stifles. METHODS: Twenty-one Norfolk rabbits were submitted to cranial cruciate ligament transection of the left stifle. After six weeks of the surgery, the rabbits were randomized assigned into three groups: G1 (control) - saline solution (0.9%); G2 - hyaluronic acid associated with triamcinolone; G3 - ozone gas, submitted to three intra-articular applications every seven days. RESULTS: Significant differences occurred: osteophytes at medial femoral condyle (G2 > G1, G2 > G3) on radiography exam; thickening of the medial condyle (G1 > G3, G2 > G3) on ultrasound exam; osteophytes at lateral tibial condyle (G2 > G1, G2 > G3), and medial femoral condyle (G1 > G2, G3 > G1) on computed tomography. Histologically, mean values of chondrocytes in the femur and tibia in G3 and G2 were statistically lower. CONCLUSIONS: The intra-articular injection of hyaluronic acid associated with triamcinolone accentuated degenerative joint disease by imaging and macroscopic evaluations, and by histological findings, this treatment and the ozone gas treatment showed similar effects and were inferior to the saline solution (0.9%).

Neosaxitoxin, a Paralytic Shellfish Poison phycotoxin, blocks pain and inflammation in equine osteoarthritis.

The Osteoarthritis is a chronic disease characterized by a progressive deterioration of the articular cartilage producing a strong inflammatory activity and chronic pain in patients. Horses also show osteoarthritis. Since the activation and progression of the disease are similar to that of human we developed a study model in horses. In this study, we test the effect of Neosaxitoxin, a phycotoxin from Paralytic Shellfish Poison, in the remediation of osteoarthritis equine clinical symptoms such as pain (showed in lameness) and inflammation quantifying the amounts of pro-inflammatory markers like cellular infiltration, TNF-alpha and nitric oxide in the synovial fluid obtained from the horse damaged joint. The outcomes show that Neosaxitoxin blocks pain for long lasting period (average 24.7 days). Furthermore, the amounts of pro-inflammatory markers were reduced and consequently an enhanced horse's well-being was obtained. Neosaxitoxin showed to be a candidate for establishing treatment protocols for OA, being safe and effective as a pain blocker in equine osteoarthritis.

Integrative multiomics analysis of Premolis semirufa caterpillar venom in the search for molecules leading to a joint disease.

The joint disease called pararamosis is an occupational disease caused by accidental contact with bristles of the caterpillar Premolis semirufa. The chronic inflammatory process narrows the joint space and causes alterations in bone structure and cartilage degeneration, leading to joint stiffness. Aiming to determine the bristle components that could be responsible for this peculiar envenomation, in this work we have examined the toxin composition of the caterpillar bristles extract and compared it with the differentially expressed genes (DEGs) in synovial biopsies of patients affected with rheumatoid arthritis (RA) and osteoarthritis (OA). Among the proteins identified, 129 presented an average of 63% homology with human proteins and shared important conserved domains. Among the human homologous proteins, we identified seven DEGs upregulated in synovial biopsies from RA or OA patients using meta-analysis. This approach allowed us to suggest possible toxins from the pararama bristles that could be responsible for starting the joint disease observed in pararamosis. Moreover, the study of pararamosis, in turn, may lead to the discovery of specific pharmacological targets related to the early stages of articular diseases.

Effect of intra-articular dexmedetomidine on experimental osteoarthritis in rats.

Pharmacological treatment of osteoarthritis is still inadequate due to the low efficacy of the drugs used. Dexmedetomidine via the intra-articular (i.a.) route might be an option for the treatment of osteoarthritis-associated pain. The present study assessed the analgesic and anti-inflammatory effects of dexmedetomidine administered via the i.a. route in different doses in an experimental model of rat knee osteoarthritis induced with monosodium iodoacetate. Rats were allocated to four groups with 24 animals in each group. The OA (osteoarthritis), DEX-1 (dexmedetomidine in dose of 1µg/kg) and DEX-3 (dexmedetomidine in dose of 3µg/kg) groups were subjected to induction of osteoarthritis through injection of monosodium iodoacetate (MIA) via the i.a. route on the right knee; the control group was not subjected to osteoarthritis induction. Clinical assessment was performed on day 0 (before osteoarthritis induction) and then on days 5, 10, 14, 21 and 28 after induction. Treatment was performed on day 7 via the i.a. route, consisting of dexmedetomidine in doses of 1 and 3 µg/kg, while group OA received 0.9% normal saline. The animals were euthanized on days 7, 14, 21 and 28. Samples of the synovial membrane were collected for histopathological analysis, and the popliteal lymph nodes were collected for measurement of cytokines (interleukin [IL] IL-6, tumor necrosis factor alpha [TNF-α]). Dexmedetomidine (1 and 3 µg/kg) significantly reduced the animals' weight distribution deficit during the chronic-degenerative stage of osteoarthritis and improved the pain threshold throughout the entire experiment. Histological analysis showed that dexmedetomidine did not cause any additional damage to the synovial membrane. The TNF-α levels decreased significantly in the DEX-3 group on day 28 compared with the OA group. Dexmedetomidine reduced pain, as evidenced by clinical parameters of osteoarthritis in rats, but did not have an anti-inflammatory effect on histological evaluation.

Galactomannan of Delonix regia seeds reduces nociception and morphological damage in the rat model of osteoarthritis induced by sodium monoiodoacetate.

This study investigated the effects of the protein-free galactomannan obtained from Delonix regia seeds (GM-DR) in an experimental osteoarthritis (OA) model. GM-DR was obtained from water-homogenized endosperms by collection of the supernatant and precipitation with ethanol. The remaining proteins in the galactomannan were removed by alkaline hydrolysis. Weight average molar mass (Mw) of the galactomannan was estimated in 5.8 × 105 g mol-1, presenting mannose:galactose ratio of 2.39:1. Rats received sodium monoiodoacetate (OA groups, 1 mg/25 µL) or saline (sham group) in the right tibio-tarsal joint. GM-DR (30-300 µg) was administered by intra-articular route at days 14 and 21 after OA induction. Hypernociception was evaluated daily by the measurement of the mechanical threshold required to cause joint flexion and paw withdrawal reflex. The 56-day animal groups were euthanized for joint histopahological analysis using the OARSI score system. Lower doses of GM-DR (30 and 100 µg) promoted antinociception from day 15 until the endpoint at day 56. Joint damage was reduced by GM-DR administration (100 µg) in OA-subjected animals, compared to the vehicle-treated OA group (5.9 ± 1.8 vs 19.0 ± 1.8, respectively, p < 0.05). Conclusion: Both antinociception and damage reduction suggest that Delonix regia galactomannan is a promising approach for osteoarthritis therapy.

Reduction of osteoarthritis severity in the temporomandibular joint of rabbits treated with chondroitin sulfate and glucosamine.

Osteoarthritis is a degenerative disease that causes substantial changes in joint tissues, such as cartilage degeneration and subchondral bone sclerosis. Chondroitin sulfate and glucosamine are commonly used products for the symptomatic treatment of osteoarthritis. The aim of the present study was to investigate the effects of these products when used as structure-modifying drugs on the progression of osteoarthritis in the rabbit temporomandibular joint. Thirty-six New Zealand rabbits were divided into 3 groups (n = 12/group): control (no disease); osteoarthritis (disease induction); and treatment (disease induction and administration of chondroitin sulfate and glucosamine). Osteoarthritis was induced by intra-articular injection of monosodium iodoacetate. Animals were killed at 30 and 90 days after initiation of therapy. The treatment was effective in reducing disease severity, with late effects and changes in the concentration of glycosaminoglycans in the articular disc. The results indicate that chondroitin sulfate and glucosamine may have a structure-modifying effect on the tissues of rabbit temporomandibular joints altered by osteoarthritis.

Comparative study of osteoarthritis induced by monoiodoacetate and papain in rabbit temporomandibular joints: macroscopic and microscopic analysis.

BACKGROUND: Osteoarthritis (OA) is a chronic, progressive, degenerative pathology. Inducing OA in an animal model is useful for studying the pathology and testing the effectiveness of new treatments. The object of the present study was to determine the macroscopic and microscopic changes occurring in rabbit temporomandibular joints (TMJ) at 15, 30 and 45 days after induction of OA by monoiodoacetate (MIA) and papain. MATERIALS AND METHODS: Twenty two male rabbits were used in the experiment, divided into three groups: a control group (n = 4) and two experimental groups, MIA (n = 9) and papain (n = 9). The progress of the disease was analysed at 15, 30 and 45 days after induction of OA. Morphological and histological analyses were carried out of the joint disc and the mandibular condyle. RESULTS: The most evident changes were expressed in the condyle and disc of joints with OA induced by MIA. The condyles presented deformation, fissures and loss of joint surface, the chondrocytes lost their morphology and organisation. In more advanced stages there was loss of the mid zone of the joint disc. CONCLUSIONS: The effects of papain were associated with condyle deformation, disorientation of the chondrocytes in the middle layer, and proliferation in deep zones; there was also an increase in the extracellular matrix. Both inductors generated changes in the TMJ and its joint surfaces; MIA was more effective and coincided more closely with the classic signs of the evolution of OA.

Descripción histológica de los daños ocasionados por monoiodo acetato de sodio en articulación humeral de rata / Histologyc description of monosodium iodoacetate damage in rat humeral joint

La inyección con monoiodo acetato de sodio (MIA) es ampliamente utilizada para producir osteoartritis en diversas articulaciones. El objetivo fue describir los daños histológicos provocados por MIA en la articulación humeral de rata. Se inyectó 0,1 mL de mezcla de 0,5 mg de MIA disuelto en 10 mL de solución fisiológica en la articulación humeral izquierda de 21 ratas SpragueDawley. Como control se utilizó la articulación derecha de cada rata. Se realizó la eutanasia a las 4, 8 y 12 semanas post inyección en grupos de 7 ratas. Los miembros mantenidos en formalina tamponada al 10% fueron descalcificados con EDTA por tres meses. Para la evaluación histológica se realizó la inclusión en parafina y se realizaron cortes coronales de 5 µm de espesor, para posterior tinción con azul de toluidina. En el cartílago sano, se observó una superficie lisa sin fisuras, todas las células de las zonas del cartílago se observaron normales. Se observaron cambios en el cartílago articular a partir de las 4 semanas post inyección, los condrocitos de la zona radial hipertróficos con gran producción de proteoglicanos. A las 12 semanas post inyección, se observa un gran deterioro, el espacio articular se ve disminuido, La superficie del cartílago se observa con fisuras y grietas que llegan hasta la zona radial. Las células alrededor de estas fisuras han desaparecido. Se observa una pérdida prominente de proteoglicanos debido a la débil tinción con azul de toluidina. La inyección articular con MIA produce lesiones similares a la OA. La gran ventaja de la OA inducida por MIA, es la facilidad de su aplicación y la rapidez en la progresión de OA.

Injection with monoiode sodium acetate (MIA) is widely used to produce osteoarthritis in various joints. The aim of this work was to describe the histological damage caused by MIA in the rat humeral joint; 0.1 mL of 0.5 mg mixture of MIA dissolved in 10 mL of physiological solution was injected into the left humeral joint of 21 Sprague-Dawley rats. As a control, the right joint of each rat was used. Euthanasia was performed at 4, 8 and 12 weeks post injection in groups of 7 rats. The samples maintained in 10 % buffered formalin were descaled with EDTA for three months. For histological evaluation, paraffin inclusion was performed and 5 µm thick coronal cuts were made for subsequent staining with toluidine blue. In the healthy cartilage, a smooth surface was observed, all cells in the cartilage areas were normal. Changes in articular cartilage were observed after 4 weeks post injection, hypertrophic radial chondrocytes with high proteoglycan production. At 12 weeks post injection, a great deterioration was observed, the articular space was diminished. The surface of the cartilage was observed with fissures and cracks that reach the radial zone. The cells around these fissures have disappeared. A prominent loss of proteoglycans was observed due to weak toluidine blue staining. Joint injection with MIA produced lesions similar to OA. The great advantage of the OA induced by MIA, is the ease of its application and the rapidity in the progression of OA.

Effects of Extract of Arrabidaea chica Verlot on an Experimental Model of Osteoarthritis.

The aim of this study was to analyze the analgesic potential of Arrabidaea chica extract (EHA) as an alternative to osteoarthritis (OA) treatment. Thus, the extract was initially evaluated by the cyclooxygenase inhibition test. The analgesic effect of the extract, in vivo, was also verified in a model of OA induced by sodium monoiodoacetate (2 mg). EHA was administered to rats at doses of 50, 150, and 450 mg/kg between 3 and 25 days after OA induction. The animals were clinically evaluated every 7 days, euthanized at 29 days, and the liver, spleen, kidney and knee collected for histopathological analysis. The chemical composition of EHA was identified by HPLC-MS and the identified compounds submitted to molecular docking study. The results showed that the extract promoted cyclooxygenase inhibition and produced significant improvements in disability, motor activity, hyperalgesia, and OA-induced allodynia parameters, in addition to improvements in the radiological condition of the knees (but not observed in the histopathological study). Chemically the extract is rich in flavonoids. Among them, we evidence that amentoflavone showed very favorable interactions with the enzyme COX-2 in the in silico analysis. Thus, it is concluded that A. chica has important analgesic properties for the treatment of OA.

Involvement of TLR4 in the protective effect of intra-articular administration of curcumin on rat experimental osteoarthritis.

PURPOSE: In view of the principal role of Toll-like receptor 4 (TLR4) in mediating sterile inflammatory response contributing to osteoarthritis (OA) pathogenesis, we used lipopolysaccharide (LPS), a known TLR4 activator, to clarify whether modulation of TLR4 contributed to the protective actions of intra-articular administration of curcumin in a classical rat OA model surgically induced by anterior cruciate ligament transection (ACLT). METHODS: The rats underwent ACLT and received 50µl of curcumin at the concentration of 1 mg mL-1 and 10 µg LPS by intra-articular injection once a week for 8 weeks. Morphological changes of the cartilage and synovial tissues were observed. Apoptotic chondrocytes were detected using TUNEL assay. The concentrations of IL-1ß and TNF-ɑ in synovial fluid were determined using ELISA kits. The mRNA and protein expression levels of TLR4 and NF-κB p65 were detected by real-time PCR and Western blotting, respectively. RESULTS: Intra-articular administration of curcumin significantly improved articular cartilage injury, suppressed synovial inflammation and down-regulated the overexpression of TLR4 and its downstream NF-κB caused by LPS-induced TLR4 activation in rat osteoarthritic knees. CONCLUSION: The data suggested that the inhibition of TLR4 signal might be an important mechanism underlying a protective effect of local curcumin administration on OA.

Involvement of TLR4 in the protective effect of intra-articular administration of curcumin on rat experimental osteoarthritis

Abstract Purpose In view of the principal role of Toll-like receptor 4 (TLR4) in mediating sterile inflammatory response contributing to osteoarthritis (OA) pathogenesis, we used lipopolysaccharide (LPS), a known TLR4 activator, to clarify whether modulation of TLR4 contributed to the protective actions of intra-articular administration of curcumin in a classical rat OA model surgically induced by anterior cruciate ligament transection (ACLT). Methods The rats underwent ACLT and received 50μl of curcumin at the concentration of 1 mg mL-1 and 10 μg LPS by intra-articular injection once a week for 8 weeks. Morphological changes of the cartilage and synovial tissues were observed. Apoptotic chondrocytes were detected using TUNEL assay. The concentrations of IL-1β and TNF-ɑ in synovial fluid were determined using ELISA kits. The mRNA and protein expression levels of TLR4 and NF-κB p65 were detected by real-time PCR and Western blotting, respectively. Results Intra-articular administration of curcumin significantly improved articular cartilage injury, suppressed synovial inflammation and down-regulated the overexpression of TLR4 and its downstream NF-κB caused by LPS-induced TLR4 activation in rat osteoarthritic knees. Conclusion The data suggested that the inhibition of TLR4 signal might be an important mechanism underlying a protective effect of local curcumin administration on OA.

CBCT analysis of rabbit temporomandibular joints with osteoarthrosis induced by monoiodoacetate and papain / Análisis por TCCB de la articulación temporomandibular de conejos con osteoartrosis inducida por monoiodoacetato y papaina

Osteoarthrosis (OA) is a degenerative disease characterized by loss of joint cartilage, remodelling of the subchondral bone, narrowing of joint spaces and the formation of osteophytes. Animal models are used to study the mechanisms of OA, as well as to test the effects of anti-osteoarthrosis drugs. The objective of the present study was to determine the changes identifiable by imaging techniques occurring in rabbit temporomandibular joints (TMJ) at 15, 25 and 45 days after OA inducement by monoiodoacetate (MIA) and papain. The imaging technology used was cone-beam computerised tomography (CBCT). The model animals were 22 young adult male New Zealand rabbits, divided randomly into three study groups: Four rabbits in the control group, nine in the papain experimental group and nine in the monoiodoacetate (MIA) experimental group. OA was induced by arthrocentesis in the lower compartment of both TMJs. The rabbits were examined by CBCT at 15, 25 and 45 days after the injection of MIA and papain. The mandibular condyles presented loss of their rounded shape, deformation of the condyle or mandibular fossa, cortical irregularity, cortical wear and changes in the dimensions of the condyle. OA induction by MIA and papain generates changes observable by CBCT in the dimensions of the mandibular condyle in rabbits. Both inducers promote signs compatible with OA on the joint surfaces of the TMJ; MIA promotes more expressive changes.

La osteoartrosis (OA) es una enfermedad degenerativa caracterizada por la pérdida de cartílago articular, remodelación ósea subcondral, estrechamiento del espacio articular y formación de osteofitos. El modelo animal es utilizado para estudiar los mecanismos de la OA, así como testar el efecto de drogas anti-osteoartrosis. El objetivo de este estudio fue determinar los cambios imagenológicos, mediante tomografía computarizada cone-beam (TCCB), que se generan en 15, 25 y 45 días, luego de la inducción de OA por medio de Monoiodoacetato (MIA) y Papaína sobre la ATM de conejos. Fueron utilizados 22 conejos machos, adultos jóvenes, de raza New Zealand divididos aleatoriamente en 3 grupos de estudio: 4 conejos para un grupo control, 9 conejos para el grupo experimental con Papaína y 9 conejos para el grupo experimental con monoiodoacetato (MIA). Se realizó la inducción de OA por la técnica de artrocentesis en el compartimiento inferior de ambas ATMs. Se les realizó examen de TCCB en los días 15, 25 y 45 tras la inyección de MIA y de papaina. Los cóndilos mandibulares presentaron pérdida de forma redondeada de cóndilo, deformidad de cóndilo o fosa mandibular, irregularidad de corticales, desgaste de corticales, cambio de dimensiones de cóndilo. La inducción de OA por medio de MIA y papaína genera cambios en la dimensión del cóndilo mandibular de conejos observables a través de TCCB. Además, ambos inductores promueven signos compatibles con OA en las superficies articulares de la ATM, siendo que la MIA promueve cambios más expresivos.

Effects of intra-articular injection of mesenchymal stem cells associated with platelet-rich plasma in a rabbit model of osteoarthritis.

The current study aims to evaluate the macroscopic and histological effects of autologous mesenchymal stem cells (MSC) and platelet-rich plasma on knee articular cartilage regeneration in an experimental model of osteoarthritis. Twenty-four rabbits were randomly divided into four groups: control group, platelet-rich plasma group, autologous MSC undifferentiated group, and autologous MSC differentiated into chondrocyte group. Collagenase solution was used to induce osteoarthritis, and treatments were applied to each group at 6 weeks following osteoarthritis induction. After 60 days of therapy, the animals were euthanized and the articular surfaces were subjected to macroscopic and histological evaluations. The adipogenic, chondrogenic, and osteogenic differentiation potentials of MSCs were evaluated. Macroscopic and histological examinations revealed improved tissue repair in the MSC-treated groups. However, no difference was found between MSC-differentiated and undifferentiated chondrocytes. We found that MSCs derived from adipose tissue and platelet-rich plasma were associated with beneficial effects in articular cartilage regeneration during experimental osteoarthritis.

Isolated and combined effects of photobiomodulation therapy, topical nonsteroidal anti-inflammatory drugs, and physical activity in the treatment of osteoarthritis induced by papain.

Osteoarthritis (OA) is a chronic inflammatory disease and is characterized as a degenerative process. This study aimed to evaluate and compare the effects of a topical nonsteroidal anti-inflammatory drug (NSAID), physical activity, and photobiomodulation therapy (PBMT) applied alone and/or in combination between them in an experimental model of knee OA. OA was induced by injection of papain in the knees of rats. After 21 days, the animals started to be treated with the above treatment. Histological analysis shows that the experimental model of OA induction causes morphological changes consistent with the disease, and among treatments, the PBMT is the most effective for reducing these changes. Moreover, the results demonstrate that PBMT and NSAID reduce the total number of cells in the inflammatory infiltrate (p<0.05) and PBMT was the most effective for reducing the activity of myeloperoxidase (p<0.05). Finally, we observed that both NSAID and PBMT were effective for reducing the gene expression of MMP-3 (p<0.05), but in relation to the gene expression of MMP-13, PBMT was the most effective treatment (p<0.05). The results of this study indicate that PBMT is the most effective therapy in stopping disease progression, and improving inflammatory conditions observed in OA.

Histaminergic Pharmacology Modulates the Analgesic and Antiedematogenic Effects of Spinally Injected Morphine.

BACKGROUND: Histamine receptors are known to participate in spinal cord nociceptive transmission, and previous studies have suggested that histaminergic receptors are involved in the analgesic effects of morphine. Herein, we investigated the effect of intrathecal injection of histaminergic agonists and antagonists in a model of acute articular inflammation and their interaction with morphine. METHODS: After carrageenan injection in the right knee joint, articular incapacitation was measured hourly, for up to 6 hours, by the paw elevation time during 1-minute periods of stimulated walking. Inflammatory edema was also assessed hourly by determining an increase in articular diameter. Spinal treatments were administered 20 minutes before knee-joint carrageenan injection and were compared with the saline-treated control group. RESULTS: Intrathecally injected histamine increased incapacitation and articular edema, whereas the H1R antagonist, cetirizine, decreased both parameters. The H3R agonist, immepip, decreased both incapacitation and edema, but the H3R antagonist, thioperamide, increased both incapacitation and edema. Morphine inhibited both incapacitation and edema. Furthermore, combining a subeffective dose of morphine with cetirizine or immepip potentiated the analgesic and antiedematogenic effect. CONCLUSIONS: Histamine seems to act at the spinal level via H1 and H3 receptors to modulate acute arthritis in rats. An H1R antagonist and H3R agonist were found to potentiate the analgesic and antiedematogenic effects of morphine, suggesting that histaminergic and opioid spinal systems may be explored for means of improving analgesia, as well as peripheral anti-inflammatory effects.