Evaluation of long-term antinociceptive properties of stabilized hyaluronic acid preparation (NASHA) in an animal model of repetitive joint pain.
Evaluation of long-term antinociceptive properties of stabilized hyaluronic acid preparation (NASHA) in an animal model of repetitive joint pain.
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DOI：
10.1186/ar3394
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发表时间：
2011-07-07
影响因子：
4.9
通讯作者：
Schaible HG
中科院分区：
文献类型：
--
作者：
Boettger MK;Kümmel D;Harrison A;Schaible HG
关于将透明质酸制剂注射到骨关节炎关节中是否可以减轻疼痛，临床试验提供了有争议的结果。临床研究的问题可能是关节内注射的显着安慰剂效应、疾病的不同严重程度和进展速度等。我们假设，使用临床前疼痛模型可能有助于阐明某种透明质酸在关节内注射后是否发挥抗伤害作用。在本研究中，我们主要在缓激肽/前列腺素 E2 (PGE2) 模型中测试了非动物源稳定透明质酸 (NASHA) 的推定抗伤害作用，NASHA 是一种用于关节内治疗 OA 的稳定透明质酸凝胶。我们建立了 NASHA 的剂量反应关系，并将 NASHA 与临床使用的不同配方的其他透明质酸进行了比较。为了诱导短暂的关节疼痛发作，在短暂麻醉期间将缓激肽和 PGE2 重复注射到大鼠膝关节的单侧关节内。建立药物前伤害性反应后，单次关节内注射不同浓度的盐水或 NASHA，并在 NASHA 后长达 56 天监测对进一步缓激肽/PGE2 注射的疼痛反应。此外，将获得的有效剂量与 Hylan GF20 和透明质酸钠的临床定义浓度进行比较。主要结果指标是膝关节原发性机械痛觉过敏和疼痛引起的负重。注射后第 1 天，与盐水相比，所有测试的透明质酸制剂均显示出 >50% 的镇痛效果。单次注射较高剂量的 NASHA（50、75 和 100 μl）可发挥长达 56 天的镇痛作用。当大鼠膝关节注射量适应人体临床注射量时，交联NASHA和Hylan GF20的镇痛作用持续时间比非交联透明质酸钠更长（NASHA效果略好于Hylan GF20）。在关节痛的缓激肽/PGE2 模型中，与盐水相比，单次注射所有透明质酸制剂可提供显着的镇痛作用。交联乙酰透明质酸制剂NASHA和Hylan GF20的抗伤害作用的持续时间似乎更长。此外，凝胶珠结构仅允许缓慢释放透明质酸（NASHA），甚至可以增强这种持久的抗伤害作用。
Clinical trials provided controversial results on whether the injection of hyaluronan preparations into osteoarthritic joints reduces pain. Problems of clinical studies may be the substantial placebo effects of intra-articular injections, different severity and rate of progression of the disease and others. We hypothesize that the use of preclinical pain models may help to clarify whether a certain hyaluronan exerts antinociceptive effects upon intra-articular injection. In the present study we tested in the bradykinin/prostaglandin E2 (PGE2) model primarily the putative antinociceptive effect of stabilized hyaluronic acid from a non animal source (NASHA), a stabilized hyaluronic acid based gel for intra-articular treatment of OA. We established a dose-response relationship for NASHA and we compared NASHA to other hyaluronans with different formulations that are in clinical use. To induce transient joint pain episodes bradykinin and PGE2 were repetitively administered intra-articularly and unilaterally into rat knee joints during short anaesthesia. After establishment of the predrug nociceptive responses, a single intra-articular injection of saline or NASHA at different concentrations was administered and pain responses to further bradykinin/PGE2 injections were monitored up to 56 days after NASHA. Furthermore, the obtained effective dose was compared to clinically defined concentrations of Hylan GF20 and sodium hyaluronate. The primary outcome measures were primary mechanical hyperalgesia at the knee joint and pain-induced weight bearing. On day 1 after injection, all tested hyaluronan preparations showed an antinociceptive effect >50% compared to saline. Single injections of higher doses of NASHA (50, 75 and 100 μl) were antinociceptive up to 56 days. When injection volumes in rat knee joints were adapted to clinical injection volumes in humans, the antinociceptive effects of the cross-linked NASHA and Hylan GF20 had a longer duration than that of the non cross-linked sodium hyaluronate (with a slightly better effect of NASHA than Hylan GF20). In the bradykinin/PGE2 model of joint pain a single injection of all hyaluronan preparations provided significant antinociceptive effects compared to saline. It appeared that the duration of the antinociceptive effect of the cross-linked hyaluronan preparations NASHA and Hylan GF20 was more prolonged. In addition, the gel beads structure allowing only a slow release of hyaluronic acid (NASHA) may even enhance this prolonged antinociceptive effect.
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影响因子：
15.1
作者：
Boettger, Michael Karl;Weber, Konstanze;Schaible, Hans-Georg
通讯作者：
Schaible, Hans-Georg
影响因子：
27.4
作者：
Jorgensen, Anette;Stengaard-Pedersen, Kristian;Frimer-Larsen, Helle
通讯作者：
Frimer-Larsen, Helle
影响因子：
7
作者：
Jones, AC;Pattrick, M;Doherty, M
通讯作者：
Doherty, M
影响因子：
--
作者：
BALAZS, EA;WATSON, D;ROSEMAN, S
通讯作者：
ROSEMAN, S
影响因子：
--
作者：
Boettger, Michael K.;Hensellek, Susanne;Schaible, Hans-Georg
通讯作者：
Schaible, Hans-Georg