Deficits in spontaneous burrowing behavior in the rat bilateral monosodium iodoacetate model of osteoarthritis: an objective measure of pain-related behavior and analgesic efficacy

被引：46

作者：

Bryden, L. A. ^{[1
]}

Nicholson, J. R. ^{[1
]}

Doods, H. ^{[1
]}

Pekcec, A. ^{[1
]}

机构：

[1] Boehringer Ingelheim Pharma GmbH & Co KG, Div Res Germany, D-88397 Biberach, Germany

来源：

OSTEOARTHRITIS AND CARTILAGE | 2015年 / 23卷 / 09期

关键词：

Burrowing; Monosodium iodoacetate; Spontaneous behavior; Pain; Rat; KNEE-JOINT INFLAMMATION; PHARMACOLOGICAL CHARACTERIZATION; NEUROPATHIC PAIN; NEURONAL INJURY; LABORATORY MICE; NERVE INJURY; RODENT MODEL; INHIBITOR; HIP; MONOIODOACETATE;

D O I：

10.1016/j.joca.2015.05.001

中图分类号：

R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学（修复外科学）];

学科分类号：

摘要：

Objective: To characterize deficits in burrowing behavior - an ethologically-relevant rodent behavior - in the monosodium iodoacetate (MIA) rat model of osteoarthritis (OA), and the sensitivity of these deficits to reversal by analgesic drugs of both prototypical and novel mechanisms of action. A second objective was to compare the burrowing assay to a spontaneous locomotor activity (sLA) assay. Method: Male Wistar Han rats (200-220 g) received intrarticular (i.a.) injections of MIA or saline for sham animals. A deficit in the amount of sand burrowed from steel tubes filled with 2.5 kg of sand was used as a measure of pain-related behavior, and sensitivity to reversal of these deficits by analgesic drugs was assessed in bilaterally MIA-injected rats. Results: Bilateral MIA injections induced a significant impairment of burrowing behavior, which was concentration-dependent. The temporal pattern of the deficits was biphasic: a large deficit at 3 days post-injection, resolving by day 14 and returning at the 21 and 28 day time points. At the 3 day time point ibuprofen, celecoxib and an anti-nerve growth factor (NGF) monoclonal antibody (mAb) were able to significantly reinstate burrowing behavior, whereas the fatty acid amide hydrolase (FAAH) inhibitor PF-04457845 and morphine displayed no reversal effect. Morphine impaired burrowing behavior at 3 mg/kg in sham animals. Deficits in rearing frequency in the locomotor activity assay proved irreversible by analgesics. Conclusion: Burrowing behavior provides an objective, non-reflexive read-out for pain-related behavior in the MIA model that has predictive validity in detecting analgesic efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) and an anti-NGF mAb. (C) 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

引用

页码：1605 / 1612

页数：8

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