Dynamic weight bearing is an efficient and predictable method for evaluation of arthritic nociception and its pathophysiological mechanisms in mice.

Andreza U Quadros,Miriam M Fonseca,Thiago M Cunha,Fernando Q Cunha,Larissa G Pinto,Ricardo Kusuda

doi:10.1038/srep14648

Andreza U Quadros, Miriam M Fonseca + Show 4 more

Open Access

https://doi.org/10.1038/srep14648

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Journal: Scientific Reports	Publication Date: Oct 29, 2015
Citations: 53	License type: CC BY 4.0

Affiliation: Universidade de São Paulo

Abstract

The assessment of articular nociception in experimental animals is a challenge because available methods are limited and subject to investigator influence. In an attempt to solve this problem, the purpose of this study was to establish the use of dynamic weight bearing (DWB) as a new device for evaluating joint nociception in an experimental model of antigen-induced arthritis (AIA) in mice. AIA was induced in Balb/c and C57BL/6 mice, and joint nociception was evaluated by DWB. Western Blotting and real-time PCR were used to determine protein and mRNA expression, respectively. DWB detected a dose- and time-dependent increase in joint nociception during AIA and was able to detect the dose-response effects of different classes of analgesics. Using DWB, it was possible to evaluate the participation of spinal glial cells (microglia and astrocytes) and cytokines (IL-1β and TNFα) for the genesis of joint nociception during AIA. In conclusion, the present results indicated that DWB is an effective, objective and predictable test to study both the pathophysiological mechanisms involved in arthritic nociception in mice and for evaluating novel analgesic drugs against arthritis.

Highlights

We intend to use Dynamic Weight Bearing (DWB) to investigate the pathophysiological mechanisms involved in the induction and maintenance of arthritic pain, focusing on the role of glial cells
The i.a. injection of methylated bovine serum albumin (mBSA) in immunized LysM-enhanced green fluorescent protein (eGFP) mice produced dose- (10–100 μ g/joint) and time- (1–96 h) related increases in joint fluorescence compared with the vehicle-injected group, suggesting an increase in the recruitment of leukocytes to local sites of inflammation (Fig. 1A,B)
The mBSA challenge in sham-immunized C57BL/6 mice did not produce any change in weight distribution between injected and non-injected hind limbs (Supplementary Figure 1) antigen-induced arthritis (AIA)-induced nociception was evaluated by femur-tibial flexion reflex model using electronic von Frey (Supplementary Figure 2)[23]

Summary

Introduction

One possible alternative to address this problem is Dynamic Weight Bearing (DWB), a device that measures the difference of weight exerted by each paw on a full-sensor floor, allowing to animals walk freely without experimenter interference These characteristics make this method unique in evaluating the natural behavior of animals under nociceptive conditions. The induction and maintenance of arthritic pain might involve mechanisms occurring at different levels of the nociceptive system including peripheral (primary sensory neurons) and central sensitization (spinal and supra-spinal), neuro-immune interactions, and others[6,7,8] Among these mechanisms, the participation of glial cells has gained importance in the last decades[9,10,11,12]. We intend to use DWB to investigate the pathophysiological mechanisms involved in the induction and maintenance of arthritic pain, focusing on the role of glial cells

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