Background/Purpose:   Background/Purpose: Osteoarthritis pain remains a significant health problem due to a growing elderly population and the need for newer effective medical therapies. Osteoarthritis pain does not correlate well with radiographic severity, and loss of function in patients with osteoarthritis may result from pain, from altered biomechanics or from toxicity of analgesics. Previous studies of mice with osteoarthritis demonstrated evoked pain behaviors but no consistent change in gait or wheelrunning. Age may also alter pain behaviors in mice with arthritis. In order to better define the relationship between osteoarthritis, pain and function, we measured different types of pain behaviors in mice with osteoarthritis at a uniform age as a function of duration of arthritis and in response to different analgesic treatments.

Methods:   Chronic non-inflammatory arthritis was produced by intra-articular (IA) injection of 10 µl collagenase (COL) (10IU) into the left knee of C57BL6 male mice 4 or 6 weeks prior to pain behavior testing using evoked pain score (EPS) and automated dynamic weight bearing (ADWB) device. EPS was a tally of fights and vocalizations/min with knee palpation at 15.6 psi. Percent weight and time on each limb was measured with ADWB apparatus (Bioseb, Vitrolles, France). IA vanilloids resiniferatoxin (RTX) or capsaicin (CAP) (10µl of 0.001%RTX or 0.01% CAP) were given 7 days prior to pain testing. IA botulinum toxin A (BTX) (10µl 0.02 IU) was injected 3 days before testing. Mice underwent pain behavior testing either 4 weeks or 6 weeks after COL injection. All mice were 12 weeks old at the time of testing.

Results:   Arthritis pain behavior was low in naïve mice – EPS (0.57) and ADWB proportions for weight (40.9%) and time (97.4%) were normal. IA COL arthritis significantly increased EPS (4.0) after 4 weeks of arthritis and but had very little effect on ADWB for weight (39.7%) and time (98.0%). All IA therapies normalized EPS in arthritic mice. Forepaw compensatory weight bearing increased only from 9.3% in naïve mice to 10.9% in COL arthritic mice at 4 weeks (NS). However after 6 weeks of COL induced arthritis, the EPS was not significantly different from naive (0.8). ADWB measures for left hind-limb weight-bearing at 6 weeks dropped (to 37.6%) and time on the limb was reduced (to 95.2%). These differences were not statistically significant. However there was an increase in forepaw weight-bearing. After 6 weeks COL mice placed 15.8% weight on the forepaws (p=0.02). Both IA RTX and IA CAP normalized this compensatory forepaw weight-bearing in the 6 week arthritic mice.

Conclusion:   IA COL monoarthritis increased evoked pain behaviors in mice after 4 weeks but had little effect on spontaneous pain measured by ADWB at this timepoint. After 6 weeks of chronic arthritis, EPS measures were no longer increased, but compensatory forepaw weight-bearing was increased significantly. This compensatory weight-bearing normalized after treatment with IA neurotoxin treatment. These results suggest that both neuroadaptive and behavioral adaptive mechanisms may be at play. Normalization of weight-bearing with analgesia suggests that alterations in weight-bearing are not just due to mechanical factors.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/effect-of-chronicity-on-pain-behaviors-in-collagenase-induced-non-inflammatory-monoarthritis-in-mice/