Bert Joseph, Mahowald Maren L, Frizelle Sandra, Dorman Christopher W, Funkenbusch Sonia C, Krug Hollis E
Rheumatology Fellowship Training Program, University of Minnesota Medical School, Minneapolis, MN, USA.
Minneapolis VA Health Care System, Minneapolis, MN, USA; University of Minnesota Medical School, Minneapolis, MN, USA.
Intern Med Rev (Wash D C). 2016;2016(6).
Capsaicin (CAP) and Resiniferatoxin (RTX) are vanilloid receptor agonists that can normalize Evoked Pain Scores (EPS) and Automated Dynamic Weight Bearing (ADWB) measures in murine acute inflammatory arthritis when given by intra-articular (IA) injection. To determine whether these vanilloid receptor agonists have benefit in Complete Freund's Adjuvant (CFA) induced chronic inflammatory arthritis pain, we measured changes in ADWB and EPS in arthritic mice with and without treatment with IA CAP and RTX.
Chronic inflammatory arthritis was produced by IA injection of 30 µl of Complete Freund's Adjuvant (CFA) into the left knee of C57BL6 male mice 3 weeks prior to pain behavior testing. Mice were injected with either low or high dose IA RTX (10µl of 0.001 or 0.003%), or IA CAP (10 µL of 0.01%) 7 days prior to pain behavior testing.
Chronic Inflammatory arthritis pain produced increased EPS and reduced ADWB measures for weight bearing in the affected limb of arthritic mice compared to naïve mice. ADWB measurements for time in CFA when compared with Naive were not significantly different, but suggested off-loading the arthritic limb to the normal limb. Treatment with IA CAP or RTX 7 days prior to pain behavior testing produced significant improvement in EPS but no improvement in ADWB measures. Neither IA CAP nor IA RTX had any impact on EPS or ADWB measurements in non-arthritic mice when given 7 days prior to pain behavioral testing.
Using ADWB and EPS, we quantified pain in a murine chronic inflammatory arthritis model. IA CFA caused a significant increase in EPS and decreased ADWB measures in the affected limb. Treatment with IA RTX and CAP produced significant improvement in EPS in mice with mono-articular inflammatory arthritis. IA vanilloid treatment produced no improvement in ADWB measurements for weight and for time.
辣椒素（CAP）和树脂毒素（RTX）是香草酸受体激动剂，通过关节内（IA）注射给药时，可使小鼠急性炎症性关节炎的诱发疼痛评分（EPS）和自动动态负重（ADWB）指标恢复正常。为了确定这些香草酸受体激动剂对完全弗氏佐剂（CFA）诱导的慢性炎症性关节炎疼痛是否有益，我们测量了接受或未接受IA CAP和RTX治疗的关节炎小鼠的ADWB和EPS变化。
在疼痛行为测试前3周，通过向C57BL6雄性小鼠的左膝IA注射30μl完全弗氏佐剂（CFA）来诱发慢性炎症性关节炎。在疼痛行为测试前7天，给小鼠注射低剂量或高剂量的IA RTX（10μl的0.001%或0.003%），或IA CAP（10μL的0.01%）。
与未患关节炎的小鼠相比，慢性炎症性关节炎疼痛使关节炎小鼠患侧肢体的EPS增加，ADWB负重指标降低。与未患关节炎的小鼠相比，CFA组的ADWB测量时间无显著差异，但表明患关节炎的肢体将负重转移到了正常肢体。在疼痛行为测试前7天用IA CAP或RTX治疗可使EPS显著改善，但ADWB指标无改善。在疼痛行为测试前7天给药时，IA CAP和IA RTX对未患关节炎的小鼠的EPS或ADWB测量均无影响。
我们使用ADWB和EPS对小鼠慢性炎症性关节炎模型中的疼痛进行了量化。IA CFA使患侧肢体的EPS显著增加，ADWB指标降低。IA RTX和CAP治疗使单关节炎症性关节炎小鼠的EPS显著改善。IA香草酸治疗对ADWB的负重和时间测量无改善作用。
