Gait analysis in rats with single joint inflammation: influence of experimental factors.

Disability and movement-related pain are major symptoms of joint disease, motivating the development of methods to quantify motor behaviour in rodent joint pain models. We used observational scoring and automated methods to compare weight bearing during locomotion and during standing after single joint inflammation induced by Freund's complete adjuvant (0.12-8.0 mg/mL) or carrageenan (0.47-30 mg/mL). Automated gait analysis was based on video capture of prints generated by light projected into the long edge of the floor of a walkway, producing an illuminated image of the contact area of each paw with light intensity reflecting the contact pressure. Weight bearing was calculated as an area-integrated paw pressure, that is, the light intensity of all pixels activated during the contact phase of a paw placement. Automated static weight bearing was measured with the Incapacitance tester. Pharmacological sensitivity of weight-bearing during locomotion was tested in carrageenan-induced monoarthritis by administration of the commonly used analgesics diclofenac, ibuprofen, and naproxen, as well as oxycodone and paracetamol. Observational scoring and automated quantification yielded similar results. We found that the window between control rats and monoarthritic rats was greater during locomotion. The response was more pronounced for inflammation in the ankle as compared to the knee, suggesting a methodological advantage of using this injection site. The effects of both Freund's complete adjuvant and carrageenan were concentration related, but Freund's incomplete adjuvant was found to be as effective as lower, commonly used concentrations of the complete adjuvant. The results show that gait analysis can be an effective method to quantify behavioural effects of single joint inflammation in the rat, sensitive to analgesic treatment.

Thrombelastography.

BACKGROUND: Thromboelastography (TEG) records the continuous profiles of whole blood coagulation by measurement of the viscoelastic changes associated with fibrin polymerization, and thereby provides a global assessment of haemostatic function. In the past decades there has been an increasing interest for TEG in clinical practice. In this paper we present the rationale for the method and a discussion of the possible application of TEG. MATERIAL AND METHODS: This review is based on personal experience and literature retrieved from searches in PubMed. RESULTS AND INTERPRETATION: Currently TEG is used with standard coagulation tests to decrease the risk for bleeding and reduce the homologous blood transfusion in cardiac surgery with cardiopulmonary bypass and in liver surgery. Other applications are severe trauma, obstetric medicine, haemophilia and hypercoagulable conditions. Development of a modified TEG, using heparin in combination with reptilase and factor XIIIa, has the potential to monitor the effects of platelet inhibiting drugs. It should be kept in mind that the TEG is a global test of coagulation and therefore the need for additional haemostatic tests should be evaluated when applicable. The main advantage for TEG is an inexpensive patient near method for quick evaluation of the patient's global haemostatic system. Used by experienced hands, TEG is a valuable haemostatic test, the future of which is already present.

Changes in spontaneous behavior in rats exposed to experimental disc herniation are blocked by selective TNF-alpha inhibition.

STUDY DESIGN: Study of pain behavior in animals by observation of changes in spontaneous behavior. OBJECTIVES: To assess if selective inhibition of tumor necrosis factor alpha may reduce changes in spontaneous behavior induced by experimental disc herniation in the rat as previously reported. SUMMARY OF BACKGROUND DATA: It is known that the proinflammatory cytokine tumor necrosis factor alpha may play a key role for the nucleus pulposus-induced nerve dysfunction seen in experimental set ups. However, it is not known if tumor necrosis factor alpha is also involved in pain production induced by the same procedure. METHODS: Thirty-two rats were used for the study. Twenty-two rats had an L4-L5 disc incision combined with a displacement of the L4 dorsal root ganglion. Twelve of these rats received an intraperitoneal injection of 0.125 mL of 10 mg/mL Remicade, and the remaining 10 were left untreated. Ten rats only had the L4-L5 disc exposed and formed the control group. The day before surgery and days 1, 3, 7, 14, and 21 after surgery, the rats were videotaped from below during a 20-minute period. The duration of four specific behaviors were determined and compared between the three experimental groups at each time point. RESULTS: Similar to a previous study, the nontreated showed increased signs of focal pain behavior (rotation of the head towards the operated leg and lifting of the operated leg) during the first 7 postoperative days. Treatment with the tumor necrosis factor alpha-inhibitor infliximab significantly reduced this behavior. At day 14, there were no differences between the groups, and at day 21, the nontreated group displayed reduced locomotion and increased immobility, similar to previous observations. Tumor necrosis factor alpha inhibition also seemed to reduce these behaviors. CONCLUSIONS: The data of the study clearly indicate a role for tumor necrosis factor alpha in the studied behavior changes after experimental disc herniation in the rat. Clinical trials must be performed in order to assess if there may be a clinical use for tumor necrosis factor alpha inhibition in the treatment of sciatica due to disc herniation.

Pathogenesis of sciatic pain: a study of spontaneous behavior in rats exposed to experimental disc herniation.

STUDY DESIGN: A new way to study pain in experimental animals without handling of the animals and based on registration of spontaneous behavior using video recordings. OBJECTIVES: To evaluate if experimental disc herniation in the rat may induce changes in spontaneous behavior. SUMMARY OF BACKGROUND DATA: The knowledge regarding the basic pathophysiologic mechanisms of sciatica has increased dramatically during the last decade. However, studies have mainly assessed nerve dysfunction rather than pain. Existing methods to study pain generally comprise a certain amount of handling and registration of changes in sensory thresholds. In the present study we introduce a new way to assess pain that focuses on changes in behavior rather than on changes in thresholds. METHODS: Forty rats were divided equally into four experimental series: sham exposure of the left L4 dorsal root ganglion, exposure of the left L4 dorsal root ganglion and incision of the L4-L5 disc, exposure and slight displacement of the left L4 dorsal root ganglion, and combination of disc incision and displacement. The rats were videotaped the day before surgery and on day 1, 3, 7, 14, and 21 after surgery. Spontaneous behavior was categorized into 10 behaviors and recorded during 20 minutes of observation. RESULTS: Disc incision and displacement per se did not induce any behaviors different from that observed in the sham-operated group. In the series with the combination of disc incision and displacement there was increased focal pain, seen as increased lifting of the hind paw on the operated side and increased rotation of the head toward the operated side. This pain pattern was most pronounced the day after surgery. Fourteen days after surgery there were no detectable differences in behavior between this group and the sham group. At day 21 after surgery, however, another picture of increased immobility and decreased locomotion was seen in this group, possibly indicating more generalized pain. CONCLUSIONS: The study demonstrates that it is possible to detect changes in spontaneous behavior after experimental disc herniation. However, such changes may only be seen if disc incision and slight mechanical deformation are combined. This is in agreement with previous clinical and experimental observations. The present model allows for convenient assessment of pain in a way that focuses on spontaneous behavior rather than changes in pain thresholds and that reduces the interference of the researcher and environment on the outcome of the assessment.