Session Information
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose:
Bone histomorphometry can define OA changes in rodents and in Antigen-Induced arthritis (AIA) in rats. We produced painful inflammatory monoarthritis in mouse knees with IA CFA. IA neurotoxins reduced pain behaviors in murine CFA arthritis. Ttreatment with anti-nerve growth factor in humans rarely produced rapid joint destruction requiring arthroplasty. We used micro CT of knees to correlate pain behaviors with histomorphometric bone changes and to determine whether IA neurotoxin treatment worsened changes.
Methods:
Chronic Inflammatory arthritis was produced by IA injection of 30 µl CFA into the left knee of C57BL6 male mice 3 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) and capsaicin (CAP) (10µl each of 0.001%RTX, 0.003% RTX or 0.01% CAP) were given 7 days prior to pain testing. IA botulinum toxin A (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 in 1/mm) were calculated from coronal slices using 3D Calculator (Erasmus Medical Center, Rotterdam, Netherlands).
Results:
Arthritis pain behavior was low in naïve mice – EPS (0.5) and ADWB proportions for weight (40.9%) and time (97.4%) were normal. IA CFA arthritis significantly increased EPS (2.5) and decreased ADWB for weight (34.1) and time (92.3). Arthritic knees had significantly reduced BV/TV (42.4 vs 50.3%), Tb.Th (252 vs 352 µm), and increased Tb.S (183 vs 112 µm) compared to naive knees. There was a significant negative linear relationship between EPS and BV/TV (R2= 0.626, p<.05) with higher EPS when BV/TV was lower. ADWB measures trended in the same direction but were not statistically significant. IA neurotoxin treatments did not decrease BV/TV or Tb.Th or increase Tb.S. High dose IA-RTX in CFA mice normalized Tb.Th but not Tb.S or BV/TV.
Conclusion:
We confirmed that IA CFA monoarthritis increased evoked and spontaneous pain behaviors. MicroCT measured significant changes in BV/TV proportion, Tb.Th and Tb.Sp in CFA inflammatory arthritis. These findings are consistent with bone histomorphometry in rats with AIA. IA neurotoxins treatments with BOT, RTX and CAP did not worsen these subchondral changes. Interestingly high dose IA-RTX actually normalized Tb.Th. The negative relationship between BV/TV proportion and pain behaviors (ie increased pain with lowest BV/TV) suggests that more severe arthritic subchondral structural changes may be associated with increased pain behaviors.
To cite this abstract in AMA style:
Krug HE, Bert J, Abbass F, Dorman CW, Frizelle S, Mahowald ML. Subchondral Bone Structure and Pain Behaviors in Complete Freund’s Adjuvant (CFA) Monoarthritis in Mice Treated with Intra-Articular (IA) Neurotoxin [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/subchondral-bone-structure-and-pain-behaviors-in-complete-freunds-adjuvant-cfa-monoarthritis-in-mice-treated-with-intra-articular-ia-neurotoxin/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/subchondral-bone-structure-and-pain-behaviors-in-complete-freunds-adjuvant-cfa-monoarthritis-in-mice-treated-with-intra-articular-ia-neurotoxin/