Marshall K W, Theriault E, Homonko D A
Department of Surgery, University of Toronto, Ontario, Canada.
J Rheumatol. 1997 Sep;24(9):1765-8.
To investigate the effect of the neuropeptide depleting agent capsaicin on neuropeptides in both synovial and nonsynovial articular tissues and on the relative degree of joint inflammation in established antigen induced arthritis (AIA).
AIA was created in both knees in 3 cats. Once AIA was established, the left knee of each animal received a single 0.5 ml injection of capsaicin (0.3 mg/ml). Three days later, the knees were harvested and dissected into 11 regions. Eleven articular cartilage tissues from both the experimental (capsaicin) and control (non-capsaicin) knees were examined for the immunocytochemical presence of substance P (SP) and calcitonin gene related peptide (CGRP). Additionally, the synovium was examined to determine the severity of joint inflammation.
Nerve fibers immunoreactive for SP or CGRP were found in all 11 tissues in each of the non-capsaicin treated AIA knees. Both perivascular and "free" SP and CGRP immunoreactive fibers were present in all 11 articular structures. In the knees treated with capsaicin, however, 48% of the joint tissues examined completely lacked SP immunoreactivity, while 12% had no CGRP immunoreactivity. Inflammatory disease severity was not ameliorated by the single intraarticular injection of capsaicin used in this study.
These data indicate that SP and CGRP immunoreactivity is maintained in synovial and nonsynovial articular tissues of non-capsaicin treated knees during subacute joint inflammation. In the capsaicin treated AIA knees, however, there was partial neuropeptide depletion. Nerve fibers containing SP were more sensitive to the peptide depleting effects of capsaicin than were CGRP positive fibers. Depletion of SP and CGRP from some joint tissues did not correlate with a decrease in joint inflammation. Studies incorporating a broad range of dosages will be required to determine whether intraarticular treatment with capsaicin can effectively deplete neuropeptides and thereby ameliorate established inflammatory arthritis.
研究神经肽耗竭剂辣椒素对滑膜和非滑膜关节组织中神经肽的影响，以及对已建立的抗原诱导性关节炎（AIA）中关节炎症相对程度的影响。
对3只猫的双膝关节均诱发AIA。一旦建立AIA，每只动物的左膝接受单次0.5 ml辣椒素（0.3 mg/ml）注射。三天后，取出膝关节并解剖为11个区域。对来自实验（辣椒素）和对照（非辣椒素）膝关节的11个关节软骨组织进行免疫细胞化学检测，以检测P物质（SP）和降钙素基因相关肽（CGRP）的存在情况。此外，检查滑膜以确定关节炎症的严重程度。
在每个未用辣椒素处理的AIA膝关节的所有11个组织中均发现了对SP或CGRP呈免疫反应的神经纤维。在所有11个关节结构中均存在血管周围和“游离”的SP和CGRP免疫反应性纤维。然而，在用辣椒素处理的膝关节中，48%的检查关节组织完全缺乏SP免疫反应性，而12%没有CGRP免疫反应性。本研究中单次关节内注射辣椒素并未改善炎症性疾病的严重程度。
这些数据表明，在亚急性关节炎症期间，未用辣椒素处理的膝关节的滑膜和非滑膜关节组织中维持着SP和CGRP免疫反应性。然而，在用辣椒素处理的AIA膝关节中，存在部分神经肽耗竭。含有SP的神经纤维比CGRP阳性纤维对辣椒素的肽耗竭作用更敏感。一些关节组织中SP和CGRP的耗竭与关节炎症的减轻无关。需要进行包含广泛剂量范围的研究，以确定关节内注射辣椒素是否能有效耗竭神经肽，从而改善已有的炎症性关节炎。
