Session Title: Biology and Pathology of Bone and Joint - Poster I
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Bone histomorphometry can define OA changes in rodents and in Antigen-Induced arthritis in rats. We previously found that pain from inflammatory monoarthritis in mouse knees correlated with bone histomorphometry measures. In order to determine whether these changes were due to pain or due to inflammation, we used micro CT to correlate pain behaviors with histomorphometric bone changes in knees from mice with collagenase induced non-inflammatory monoarthritis with and without analgesia with intra-articular (IA) vanilloids and botulinum toxin.
Methods: Chronic non-inflammatory arthritis was produced by IA injection of 10 µl collagenase (COL) (10IU) into the left knee of C57BL6 male mice 4 weeks prior to pain behavior testing using evoked pain scores (EPS) and an 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) and capsaicin (CAP) (10µl each 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. Knees were imaged on a micro-CT scanner (micro-CT40; ScanCo Medical AG, Bassersdorf, Switzerland). Subchondral trabecular bone volume fraction (BV/TV), trabecular thickness (Tb.Th in µm), trabecular spacing (Tb.S in µm), and number (Th.N/mm) were calculated from coronal slices using the ScanCo bone trabecular morphometry program.<span”>
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) but had very little effect on ADWB for weight (39.7%) and time (98.0%). Forepaw compensatory weight bearing increased only from 9.3% in naïve mice to 10.9% in COL arthritic mice. In selected mice with COL arthritis in contrast to inflammatory monoarthritis, there was no significant correlation between pain as measured by EPS or ADWB and any measure of bone histomorphometry. There was no significant difference in bone volume, trabecular number, thickness or spacing between naïve and arthritic mice. IA neurotoxin treatment of COL arthritis with either BTX or Vanilloids (RTX or CAP) did not have a consistent effect on bone histomorphometry.
Conclusion: IA COL induced monoarthritis increased EPS in mice but had little effect on spontaneous pain as measured by ADWB. MicroCT did not find significant changes in BV/TV proportion, Tb.Th or Tb.Sp in COL non-inflammatory arthritis. IA neurotoxin treatments with BTX, RTX and CAP did not affect subchondral bone. These findings are not consistent with other findings in OA rodent models or our previous results with chronic inflammatory arthritis. These results suggest that pain alone is not sufficient to produce changes in bone histomorphometry. It may be that offloading is more important and that 4 weeks is not long enough to cause gait offloading in this model. We have noted increased offloading in this model after 6 weeks. It will be important to study whether offloading with additional chronicity will change bone morphometry.
To cite this abstract in AMA style:Krug HE, Dorman CW, Frizelle S, Valen PA, Mahowald ML. Subchondral Bone Structure and Pain Behaviors in Collagenase Induced Noninflammatory Monoarthritis in Mice [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/subchondral-bone-structure-and-pain-behaviors-in-collagenase-induced-noninflammatory-monoarthritis-in-mice/. Accessed December 3, 2020.
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