Background/Purpose:  Murine models are important to study arthritis pain and new analgesics, however measuring pain in mice is challenging. The Dynamic Weight Bearing (DWB) device measures individual limb forces during spontaneous activity and time spent bearing weight on each limb. Evoked pain behaviors in mice are sensitive to change due to arthritis pain and analgesia. We hypothesized that mice with acute arthritis would have measurable changes in DWB due to joint pain and that this could be prevented by pre-treating with intra-articular (IA) capsaicin.

Objectives
We measured DWB and Evoked Pain Scores (EPS) in acute arthritis to determine if DWB correlates with EPS and whether it is a reliable measure of spontaneous pain behavior in animals with arthritis.  To test the reliability of DWB in differentiating arthritic from nonarthritic animals, some mice were pretreated with capsaicin to prevent development of arthritis.

Methods:  C57Bl6 mice were used for all experiments. Acute inflammatory arthritis was produced by IA injection of 10µl 2.5% carrageenan into the left knee 2-4 hours prior to pain behavior testing. Analgesic controls were injected with 2.5% carrageenan diluted in morphine (MOR) solution (morphine dose of 0.15µg/knee). Some mice were injected IA with capsaicin (0.305 mmol) 7 days before induction of arthritis.  DWB was measured with a Dynamic Weight Bearing apparatus (Bioseb, Vitrolles, France). Evoked pain behavior was measured by tallying fights + vocalizations/1 min with repeated firm palpation of the knee.

Results: Arthritis pain was clearly and reproducibly indicated by increased Evoked Pain Scores (EPS) in arthritic mice. DWB was significantly reduced by acute arthritis in the affected limb measured by both % weight bearing and time on the affected limb. IA MOR improved EPS but did not improve DWB significantly. Pretreatment with capsaicin abolished the increased EPS from carrageenan arthritis and normalized DWB by all measures.  IA capsaicin injection alone had no effect on DWB or EPS by day 7.

 

Mean (SEM)	Naive	Sham Injected	Acute Arthritis	MOR Rx Acute Arthritis	MOR Alone	Capsaicin Pre-treatment	Capsaicin Alone
EPS	1.25 (0.49)	1.67 (0.88)	12.75 (3.41)	5.38 (1.34))	1.88 (0.85)	0.33 (0.33)	1.67 (1.67)
DWB L/R Ratio % Weight	0.975 (0.065)	1.189 (0.134)	0.581 (0.105)	0.515 (0.128)	1.303 (0.136)	1.002 (0.134)	0.838 (0.131)
DWB L/R Ratio % Time on Limb	0.961 (0.023)	0.992 (0.027)	0.757 (0.085)	0.830 (0.084)	0.988 (0.023)	1.030(0.017)	0.967 (0.047)

Conclusion:  Pain can be quantitated in murine arthritis models using measures of DWB and EPS. EPS increased and DWB of the affected limb decreased significantly with acute inflammatory arthritis. Animals pretreated with capsaicin did not develop pain as measured by EPS or DWB. IA MOR was not effective in normalizing DWB in this small experiment, but was effective in reducing EPS in arthritic mice. DWB appears to have significant utility for measuring arthritis pain in animal models. It is sensitive to change, has good reproducibility between mice and is highly correlated with other measure of arthritis pain in mice.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-effect-of-pretreatment-with-capsaicin-on-measurement-of-arthritis-pain-by-dynamic-weight-bearing-and-evoked-pain-responses-in-an-acute-murine-arthritis-model/