RESUMO
OBJECTIVE: The purpose of this study was to investigate whether the effect of treatment with hyaluronic acid (HA) on cartilage in osteoarthritis (OA) can be determined by measuring the magnetic resonance (MR) T2 value of cartilage in an anterior cruciate ligament transection (ACLX) animal model. METHOD: Eighteen male Sprague Dawley rats were separated randomly into three groups (n=6 for each group). Group 1 was given ACLX and intra-articular (IA) normal saline (NS) injection (ACLX+NS), group 2 was given ACLX and IA HA injection (ACLX+HA), and group 3 was the sham control. The ACLX+NS and ACLX+HA groups received ACLX on the right knee at 8 weeks of age and were then treated with IA NS or HA injection once a week, respectively, for 4 weeks starting at 13 weeks of age. In the sham-control group, the right knee joint was opened surgically but ACLX was not performed at 8 weeks of age. MR T2 measurements were obtained on all rats at 8, 12, and 21 weeks of age, and histological Mankin scoring was performed at 21 weeks of age. RESULTS: Five weeks after the 4-week treatment, the MR T2 value of the ACLX right knee cartilage was significantly lower in ACLX+HA (29.58+/-1.12ms) than in ACLX+NS (32.04+/-1.39ms) (P<0.05). Five weeks after the 4-week treatment, the Mankin score of the ACLX right knee was significantly lower in ACLX+HA (3.3+/-0.81) than in ACLX+NS (7.3+/-1.03) (P<0.001). The T2 value was significantly and positively correlated with the Mankin score in the ACLX+NS (rho=0.77, P<0.05) and ACLX+HA (rho=0.69, P<0.05) groups. CONCLUSION: This study demonstrates the feasibility of quantitative MR T2 measurement in the early assessment of HA treatment efficiency in a cartilage degeneration model.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Lesões do Ligamento Cruzado Anterior , Cartilagem Articular/patologia , Ácido Hialurônico/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/farmacologia , Animais , Ligamento Cruzado Anterior/cirurgia , Artrite Experimental/patologia , Cartilagem Articular/efeitos dos fármacos , Modelos Animais de Doenças , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/farmacologia , Injeções Intra-Articulares , Imageamento por Ressonância Magnética/métodos , Masculino , Osteoartrite do Joelho/patologia , Ratos , Ratos Sprague-DawleyRESUMO
Preclinical exploration of pain processing in the brain as well as evaluating pain-relief drugs in small animals embodies the potential biophysical effects in humans. However, it is difficult to measure nociception-related cerebral metabolic changes in vivo, especially in unanesthetized animals. The present study used (18)F-fluorodeoxyglucose small-animal positron emission tomography to produce cerebral metabolic maps associated with formalin-induced nociception. Anesthesia was not applied during the uptake period so as to reduce possible confounding effects on pain processing in the brain. The formalin stimulation at the hind paw of rats resulted in significant metabolic increases in the bilateral cingulate cortex, motor cortex, primary somatosensory cortex, secondary somatosensory cortex, insular cortex, visual cortex, caudate putamen, hippocampus, periaqueductal gray, amygdala, thalamus, and hypothalamus. Among the measured areas, clear lateralization was only evident in the primary somatosensory cortex and hypothalamus. In addition, pretreatment with lidocaine (4 mg/kg, i.v.) and morphine (10 mg/kg, i.v.) significantly suppressed formalin-induced cerebral metabolic increases in these areas. The present protocol allowed identification of the brain areas involved in pain processing, and should be useful in further evaluations of the effects of new drugs and preclinical therapies for pain.