Ahmed M, Bjurholm A, Srinivasan G R, Lundeberg T, Theodorsson E, Schultzberg M, Kreicbergs A
Department of Orthopaedics, Karolinska Hospital, Stockholm, Sweden.
Regul Pept. 1995 Jan 5;55(1):85-102. doi: 10.1016/0167-0115(94)00095-f.
The effects of capsaicin on the sensory neuropeptides substance P and calcitonin gene-related peptide were analyzed in the ankle joints and dorsal root ganglia (L2-L6) of adult female Lewis rats. The study included 23 normal rats and 23 arthritic rats, all injected subcutaneously with capsaicin (total dose 200 mg/kg bw). Another two groups of animals from a previous study, i.e., 23 normal rats and 23 arthritic rats not given capsaicin served as controls. Adjuvant arthritis was induced by inoculation with heat-killed mycobacteria. The morphological distribution of sensory neuropeptides was assessed by immunohistochemistry and the tissue concentrations were determined by radioimmunoassay. In normal rats, capsaicin significantly reduced the concentrations of substance P and calcitonin gene-related peptide in ankle joints (54 and 36%, respectively) as well as dorsal root ganglia (40 and 54%, respectively). In arthritic rats those pretreated with capsaicin had significantly lower concentrations of substance P and calcitonin gene-related peptide in dorsal root ganglia (19 and 42%, respectively) compared to the arthritic controls. In the ankle joints, however, only the SP concentration was reduced (42%). Notably, this was accompanied by a 40% reduction in inflammatory response as assessed by comparing the ankle joint weights of the experimental groups. In general, there was a good correlation between the neuropeptide concentrations in ipsilateral ankle joints and the corresponding dorsal root ganglia as assessed in individual rats. The present study of adjuvant induced arthritis shows that capsaicin administration reduces the otherwise up-regulated levels of sensory neuropeptides in dorsal root ganglia and ankle joints. However, capsaicin at the dose given can only mitigate, not completely prevent the development of joint inflammation. Nonetheless, the findings suggest that antineuronal therapy targeted against specific neurotransmitters may prove useful in inflammatory joint disease.
在成年雌性Lewis大鼠的踝关节和背根神经节（L2 - L6）中分析了辣椒素对感觉神经肽P物质和降钙素基因相关肽的影响。该研究包括23只正常大鼠和23只关节炎大鼠，所有大鼠均皮下注射辣椒素（总剂量200mg/kg体重）。来自先前研究的另外两组动物，即23只正常大鼠和23只未给予辣椒素的关节炎大鼠作为对照。通过接种热灭活的分枝杆菌诱导佐剂性关节炎。通过免疫组织化学评估感觉神经肽的形态分布，并通过放射免疫测定法测定组织浓度。在正常大鼠中，辣椒素显著降低了踝关节中P物质和降钙素基因相关肽的浓度（分别为54%和36%）以及背根神经节中的浓度（分别为40%和54%）。与关节炎对照组相比，用辣椒素预处理的关节炎大鼠背根神经节中P物质和降钙素基因相关肽的浓度显著降低（分别为19%和42%）。然而，在踝关节中，只有P物质浓度降低（42%）。值得注意的是，通过比较实验组踝关节重量评估，炎症反应降低了40%。总体而言，在个体大鼠中评估时，同侧踝关节和相应背根神经节中的神经肽浓度之间存在良好的相关性。本佐剂诱导性关节炎研究表明，给予辣椒素可降低背根神经节和踝关节中原本上调的感觉神经肽水平。然而，给定剂量的辣椒素只能减轻而不能完全预防关节炎症的发展。尽管如此，这些发现表明针对特定神经递质的抗神经元疗法可能对炎性关节疾病有用。
