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SummaryAs reported in the literat ure, oral endotracheal intubat ion of rats is considered to be very difficult. Specialised equipment and complicat ed techniques have been described to perform this procedure. In our experiment we adopted a simple method, which allowedÐwithout any complicated equipmentÐthe insertion of a relatively wide tube into the trachea of rats, allowing drug administrat ion.Keywords Endotrac heal intubat ion; rat; large tube; intrat racheal aerosol drug administrat ion Endot racheal intubation in small laborat ory anim als is often used for studies of pulmonary absorption and the bioavailabi lity of various macromolecules (Patton e t a l. 1994, Smith e t a l. 1994, Niven e t a l. 1995, Lizio e t a l. 2000 ). Endotrac heal intubation allows the delivery of test substances both in¯uid form (solution or suspension) as well as by aerosol (Osaier & Oberdo Èrster 1997 ). Endotracheal intubation of rats is problemati c because of the narrow oral cavity and glottis, the dif®culty in visualizing the trachea, and the mobility of the larynx even under narcosis. Several techniques have been developed for endotracheal intubation in rats but most of them require special skill, e.g. blind oral tracheal intubation (Stark e t a l. 1981 ); or elaborat e and specially designed equipm ent, e.g. a miniature laryngoscope (Proctor & Fernando 1973 ), a ®bre-optic laryngoscope (Costa e t a l. 1986 ), or an otoscope (Weksler e t a l. 1994 ). Most of these methods are associated with a high failure rate and require considerable practice to ensure successful intubati on without oropharyngeal or endotracheal damage. Moreover, for endotracheal aerosol drug delivery, large tubes are needed in order to reduce aerosol condensation or deposition on the tube's walls. T his ensures tight contact between the tube and trachea, which avoids loss of air or aerosol during application. A relatively simple intubation can be performed using a very thin cannula, as described by Yasaki and Dyck (1991) but this method is only applicable for endotracheal instillation and can produce tracheal traum a and bleeding. We have therefore developed a simple, fast and reliable method for endotracheal intubat ion in the rat that utilizes readily available normal laboratory utensils, and which allows instillation as well as delivery of aerosol for pulmonary drug studies.

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Pain due to osteoarthritis (OA) often occurs during locomotion in the vertical direction when joints are subjected to high mechanical load, e.g. during standing up from a chair or using stairs. To investigate joint pain in OA rat models, dynamic weight-bearing or gait analysis is traditionally conducted during horizontal walking on a flat surface. However, in chronic models of OA, which are of particular translational relevance for the disease, differences in the readouts between OA and control rats are often weak and of high variability leading to an insufficient assay window for drug profiling. To measure pain-related symptoms more sensitively, we conducted a dynamic weight-bearing test in the moment of a strong voluntary mechanical load. For that, we permanently housed rats in a four-story rat colony cage (RCC) and determined hind paw forces during voluntary jumping from one level to the next. This outcome measure was named jump incapacitance. After inducing OA by destabilizing the medial meniscus (DMM), we found that during jumps the average ipsilateral over contralateral hind paw forces were significantly reduced compared with healthy controls (jump incapacitance) from early- (day 7) to late-stage disease (day 90). An intra-articular injection of Zilretta (triamcinolone acetonide extended-release injectable suspension) attenuated OA-induced jump incapacitance after 8 days compared with DMM rats receiving vehicle (p = 0.069). In contrast, a CatWalk test for gait disturbance failed to detect any significant alterations in the chronic course of the DMM model. In conclusion, the dynamic weight-bearing test during jumping represents a novel method to characterize joint pain symptoms even in a slowly progressive OA rat model. It is sensitive, observer independent, relates to clinically relevant endpoints and demonstrates backtranslation of a drug that is approved for the treatment of OA knee pain.

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