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Validating drg 945

An increase in nociceptive behaviour associated with movement and loading of affected joints was observed after intra-articular collagenase injection.With the 500 U dose of collagenase, there was a significant correlation between the behavioural and the histopathological osteoarthritis-like structural changes developed after six weeks.A model that comprises both the reproduction of the initiating events and joint tissue pathology observed in human OA as well as the induction of relevant nociceptive responses that mimic patients’ main complaints, such as increased nociception due to movement and loading on the affected joint, would certainly be a clinically-relevant model for the study of OA pain.The intra-articular (i.a.) injection of collagenase is an established model of OA that has been predominantly used to study the mechanisms underlying structural joint damage [].A six weeks time-course assessment of movement- and loading-induced nociception was performed by the Knee-Bend and Cat Walk tests.The effect of morphine, lidocaine and diclofenac on nociceptive behaviour was evaluated in animals injected with 500 U of collagenase.Movement-induced nociception was evaluated by the Knee-Bend and Cat Walk tests [] on Day 0 (before the first injection), and at one, two, three, four, five and six weeks after the first injection, until each group’s endpoint.Testing was performed blindly, always by the same experimenter.

It seems reasonable to state that the development of chronic pain in OA should not be dissociated from the structural articular changes that occur during the onset and progression of OA.Joint histopathology was scored for both doses throughout time.The expression of transient receptor potential vanilloid 1 (TRPV1) in ipsilateral dorsal root ganglia (DRG) was evaluated.One week after injection of 500 U collagenase, swelling of the injected knee and inflammation of the synovial membrane were also observed, indicating the occurrence of an early inflammatory reaction.Behavioural changes induced by the 500 U dose of collagenase were overall effectively reversed by morphine and lidocaine. TRPV1 expression increased six weeks after 500 U collagenase injection.We also tested the efficacy of morphine in reversing behavioural changes with the goal of validating them as being nociception-related, as well as the efficacy of a local anaesthetic intra-articularly injected in the knee, in order to demonstrate that the nociceptive behaviours observed are indeed originated in the knee joint.Furthermore, since there seemed to be an inflammatory reaction occurring after the injection of collagenase, we also tested the effect of the non-steroidal anti-inflammatory drug (NSAID) diclofenac in reversing the nociceptive changes observed.Here, we evaluated if the intra-articular injection of collagenase can be an alternative model to study nociception associated with osteoarthritis.Osteoarthritis was induced by two intra-articular injections of either 250 U or 500 U of collagenase into the left knee joint of adult male Wistar rats.Additionally, to determine if changes in the sensory innervation of the knee could also be observed in this model, we evaluated, in the dorsal root ganglia (DRG) from control and collagenase-injected animals, the expression of the transient receptor potential vanilloid 1 (TRPV1), an ion channel whose role in nociception is widely reported [, at a constant temperature of 22°C and controlled lighting (12 h light/12 h dark cycle).A total of 99 animals were used in this study: 72 for behavioural testing and 27 for the pharmacological evaluation, 5 per drug (15 in total) and 4 per control (12 in total).


  1. The present invention concerns methods and reagents useful in modulating gene expression in a variety of applications, including use in therapeutic, diagnostic.

  2. Differential expression of Cathepsin E in transthyretin amyloidosis from neuropathology to. We started by validating the. Journal of Neuroinflammation.


  4. MicroRNA modulation in complex regional pain. Profiling of 369 miRNAs was performed in rat DRG 4. Additional studies validating the role of the miRNAs.

  5. Animal models currently used in osteoarthritis-associated pain research inadequately reproduce the initiating events and structural pathology of human osteoarthritis.

  6. We also tested the efficacy of morphine in reversing behavioural changes with the goal of validating them as. DRG sections were. 945-954. CrossRef.

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