Validation of a new system for the automatic registration of behaviour in mice and rats

Weerd, Heleen van de; Bulthuis, R.; Bergman, Anni; Schlingmann, F; Tolboom, J; Loo, P. L. P. Van; Remie, R; Baumans, V.; Zutphen, L.F.M. van

doi:10.1016/s0376-6357(00)00135-2

Cited by 121 publications

(73 citation statements)

References 11 publications

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“…During the second stage, beginning at 8 wk after DMM surgery, behaviors indicative of movement-provoked pain were observed. When monitored overnight on a LABORAS (Laboratory Animal Behavior Observation Registration Analysis System) platform (24), DMM mice 4-wk postsurgery and age-matched naïve mice traveled similar distances (Fig. 3B).…”

Section: Wild-type Mice Develop Mechanical Allodynia and Decreases Inmentioning

confidence: 86%

“…Locomotive behaviors [distance traveled, climbing (hanging upside down from wire cage), and rearing (standing on hindlegs)] were assessed overnight by using the LABORAS (Metris) (24). A 5-mg/kg dose of CCR2 receptor antagonist (CCR2-RA) (Tocris Bioscience, RS 504393; DMSO vehicle) or a 50-μg dose of indomethacin (Tocris Bioscience #1708; DMSO vehicle) was administered intraperitoneally immediately before placement on the platform to study CCR2 inhibition effects on behaviors or analgesic reversal of behaviors, respectively.…”

Section: Laboras (Assessment Of Spontaneous Behavior)mentioning

confidence: 99%

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CCR2 chemokine receptor signaling mediates pain in experimental osteoarthritis

Miller

Tran

Das

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

242

281

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Osteoarthritis is one of the leading causes of chronic pain, but almost nothing is known about the mechanisms and molecules that mediate osteoarthritis-associated joint pain. Consequently, treatment options remain inadequate and joint replacement is often inevitable. Here, we use a surgical mouse model that captures the long-term progression of knee osteoarthritis to longitudinally assess pain-related behaviors and concomitant changes in the innervating dorsal root ganglia (DRG). We demonstrate that monocyte chemoattractant protein (MCP)-1 (CCL2) and its high-affinity receptor, chemokine (C-C motif) receptor 2 (CCR2), are central to the development of pain associated with knee osteoarthritis. After destabilization of the medial meniscus, mice developed early-onset secondary mechanical allodynia that was maintained for 16 wk. MCP-1 and CCR2 mRNA, protein, and signaling activity were temporarily up-regulated in the innervating DRG at 8 wk after surgery. This result correlated with the presentation of movement-provoked pain behaviors, which were maintained up to 16 wk. Mice that lack Ccr2 also developed mechanical allodynia, but this started to resolve from 8 wk onwards. Despite severe allodynia and structural knee joint damage equal to wild-type mice, Ccr2-null mice did not develop movement-provoked pain behaviors at 8 wk. In wild-type mice, macrophages infiltrated the DRG by 8 wk and this was maintained through 16 wk after surgery. In contrast, macrophage infiltration was not observed in Ccr2-null mice. These observations suggest a key role for the MCP-1/CCR2 pathway in establishing osteoarthritis pain.O steoarthritis is the most common joint disorder and is one of the leading causes of chronic pain (1, 2). Osteoarthritis commonly affects knees, hips, and hands and is characterized by radiographic changes (primarily joint space narrowing, subchondral bone sclerosis, and osteophytes) accompanied by clinical symptoms, most prominently pain. Treatments that alter the progression of the structural damage in the joint are not yet available. Options for treating the pain include nonsteroidal anti-inflammatory drugs, steroids, and viscosupplementation, but analgesia is often inadequate, and uncontrolled pain is the number one reason why people with osteoarthritis undergo joint-replacement surgery (3). Despite the enormous health and economic burden of osteoarthritis and associated pain (4), very few studies have examined the molecular pathways that mediate osteoarthritis pain. As in all types of chronic pain, osteoarthritis pain is the dynamic result of a complex interaction between local tissue damage and inflammation, peripheral and central sensitization, and the brain (5-7). Joint pain associated with osteoarthritis, however, has unique clinical features that provide insight into the mechanisms that cause it. First, joint pain has a strong mechanical component: it is typically triggered by specific activities (for example, climbing stairs elicits knee pain) and is relieved by rest. As structural joint disease advance...

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Section: Wild-type Mice Develop Mechanical Allodynia and Decreases Inmentioning

confidence: 86%

Section: Laboras (Assessment Of Spontaneous Behavior)mentioning

confidence: 99%

CCR2 chemokine receptor signaling mediates pain in experimental osteoarthritis

Miller

Tran

Das

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

242

281

View full text Add to dashboard Cite

show abstract

“…Here, we used an automated activity monitor (LABORAS) that quantifies many spontaneous behaviors, including climbing and grooming (13). Arthritis resulted in less time spent mobile, as reported for CFA-induced arthritis (23).…”

Section: Discussionmentioning

confidence: 99%

Collagen‐induced arthritis as a model of hyperalgesia: Functional and cellular analysis of the analgesic actions of tumor necrosis factor blockade

Inglis¹,

Notley²,

Essex³

et al. 2007

Arthritis & Rheumatism

155

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Objective. There is a disparity in the animal models used to study pain in rheumatoid arthritis (RA), which tends to be acute in nature, and models used to assess the pathogenesis of RA. The latter models, like human RA, are lymphocyte-driven and polyarthritic. We assessed pain behavior and mechanisms in collageninduced arthritis (CIA), the model of preclinical arthritis used most commonly in the field of immunology. We then validated the model using anti-tumor necrosis factor (anti-TNF) therapy, which has analgesic effects in models of inflammation as well as in human RA.Methods. CIA was induced in DBA/1 mice by immunization with type II collagen at the base of the tail. Swelling and mechanical and thermal hyperalgesia were assessed before and for 28 days after the onset of arthritis. Spontaneous behavior was assessed using an automated activity monitor. Glial activity was assessed by glial fibrillary acidic protein expression, and nerve damage was evaluated by activating transcription factor 3 expression. The actions of anti-TNF therapy on nociception were then evaluated.Results. Arthritis resulted in a decrease in the threshold for thermal and mechanical stimuli, beginning on the day of onset. Decreased spontaneous activity was also observed. A significant increase in the number of hyperplasic spinal cord astrocytes was observed beginning 10 days after the onset of arthritis. Anti-TNF therapy was profoundly analgesic, with an efficacy similar to that of cyclooxygenase 2 inhibition, and reduced astrocyte activity in CIA.Conclusion. This study shows that the CIA model is suitable for testing not only antiinflammatory but also analgesic drugs for potential use in RA, and highlights the importance of using appropriate disease models to assess relevant pain pathways.

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“…The Laboratory Animal Behavior Observation Registration and Analysis System (LABORAS; Metris, Zoetermeer, The Netherlands) is an automated system that analyzes vibrations evoked by movement of a single rodent in a cage. Patternrecognition software then classifies and quantifies behaviors, including grooming, activity, climbing, immobility, and feeding (16,17). Our system has 4 cages.…”

Section: Methodsmentioning

confidence: 99%

Regulation of pain sensitivity in experimental osteoarthritis by the endogenous peripheral opioid system

Inglis

McNamee

Chia

et al. 2008

Arthritis & Rheumatism

107

126

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Objective. OA is the most common joint disease, affecting 10-15% of people over 60 years of age. However, up to 40% of individuals with radiologic damage are asymptomatic. The purpose of this study was to assess the role of the endogenous opioid system in delaying the onset of pain in a murine model of osteoarthritis (OA).Methods. Osteoarthritis was induced by transection of the medial meniscotibial ligament. Pain was assessed by monitoring weight distribution and activity. At various times postsurgery, the opioid receptor antagonists naloxone or peripherally restricted naloxone methiodide were administered, and pain was assessed. Levels of the -opioid receptor were assessed in the nerves innervating the joint by real-time reverse transcription-polymerase chain reaction analysis.Results. As in human disease, significant joint damage occurred in mice before the onset of pain. To assess whether delayed pain was partly the result of increased endogenous opioid function, naloxone or naloxone methiodide was administered. Both opioid receptor antagonists led to pain onset 4 weeks earlier than in vehicle-treated mice, indicating a role of the peripheral opioid system in masking OA pain. The expression of the -opioid receptor in the peripheral nerves supplying the joint was transiently increased in naloxoneresponsive mice. Conclusion.These findings indicate that a temporal induction of -opioid receptors in the early stages of OA delays the onset of pain. This is of clinical relevance and may contribute to the assessment of patients presenting with pain late in the disease. Furthermore, it may point to a mechanism by which the body blocks pain perception in moderate states of tissue damage, allowing an increased chance of survival.

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Validation of a new system for the automatic registration of behaviour in mice and rats

Cited by 121 publications

References 11 publications

CCR2 chemokine receptor signaling mediates pain in experimental osteoarthritis

CCR2 chemokine receptor signaling mediates pain in experimental osteoarthritis

Collagen‐induced arthritis as a model of hyperalgesia: Functional and cellular analysis of the analgesic actions of tumor necrosis factor blockade

Regulation of pain sensitivity in experimental osteoarthritis by the endogenous peripheral opioid system

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