Intra-articular Injection of Pure Platelet-Rich Plasma Is the Most Effective Treatment for Joint Pain by Modulating Synovial Inflammation and Calcitonin Gene-Related Peptide Expression in a Rat Arthritis Model
Intra-articular Injection of Pure Platelet-Rich Plasma Is the Most Effective Treatment for Joint Pain by Modulating Synovial Inflammation and Calcitonin Gene-Related Peptide Expression in a Rat Arthritis Model
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DOI：
10.1177/0363546520924011
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发表时间：
2020-06-10
影响因子：
4.8
通讯作者：
Koga, Hideyuki
中科院分区：
文献类型：
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作者：
Araya, Naoko;Miyatake, Kazumasa;Koga, Hideyuki
背景：富血小板血浆（PRP）已成为骨关节炎（OA）的一种治疗方法。然而，富血小板血浆中白细胞浓度对OA的影响仍不清楚。目的：通过在大鼠关节炎模型中比较纯PRP、贫白细胞PRP（LP-PRP）和富白细胞PRP（LR-PRP），阐明治疗OA的最佳PRP制剂。研究设计：对照实验室研究。方法：雄性Wistar大鼠在第0天通过关节内注射碘乙酸（MIA）诱导双侧膝关节炎。将大鼠随机分配至3个给药组（纯PRP、LP-PRP和LR-PRP）之一。在第1天，将同种异体PRP注射到大鼠的右膝中，并将磷酸盐缓冲盐水注射到左膝中作为对照。测量后肢上的重量分布14天以评估疼痛行为。在第5天或第14天对大鼠实施安乐死，以进行滑膜组织和软骨的组织学评估。进行降钙素基因相关肽（CGRP）和α-平滑肌肌动蛋白的免疫组织化学染色，以确定PRP制剂诱导的疼痛缓解机制。结果如下：在所有组中，PRP增加了PRP注射膝关节的负荷分担率，在3种PRP中，纯PRP引起的作用最大（P<0.05）。与对照组相比，5天和14天后，纯PRP组的滑膜组织结构变化受到显著抑制（分别为P<0.001和P = 0.025），而对照组、LP-PRP组和LR-PRP组之间无显著差异。在第14天，仅在纯PRP组中观察到对软骨变性的抑制作用。与其他组相比，纯PRP还显著抑制髌下脂肪垫中CGRP阳性神经纤维的表达（P<0.05）。结论：在MIA诱导的关节炎模型中，纯PRP注射是减少疼痛相关行为和抑制滑膜炎症和疼痛致敏的最有效治疗。
Background: Platelet-rich plasma (PRP) has emerged as a treatment for osteoarthritis (OA). However, the effect that leukocyte concentrations in PRP have on OA remains unclear. Purpose: To clarify the optimal PRP formulation for OA treatment by comparing pure PRP, leukocyte-poor PRP (LP-PRP), and leukocyte-rich PRP (LR-PRP) in a rat arthritis model. Study Design: Controlled laboratory study. Methods: Knee arthritis was induced bilaterally in male Wistar rats with intra-articular injections of monosodium iodoacetate (MIA) on day 0. Rats were randomly assigned to 1 of 3 treatment groups (pure PRP, LP-PRP, and LR-PRP). On day 1, allogenic PRP was injected into the right knee of rats and phosphate-buffered saline was injected into the left knee as a control. Weight distribution on the hindlimbs was measured for 14 days to assess pain behavior. Rats were euthanized at day 5 or 14 for histological assessment of synovial tissue and cartilage. Immunohistochemical staining of calcitonin gene-related peptide (CGRP) and alpha-smooth muscle actin was performed to determine the mechanism of pain relief induced by the PRP preparations. Results: In all groups, PRP increased the load-sharing ratio on PRP-injected knees, with pure PRP eliciting the largest effect among the 3 kinds of PRP (P< .05). Structural changes in the synovial tissue were significantly inhibited in the pure-PRP group compared with the control group after both 5 and 14 days (P< .001 andP= .025, respectively), whereas no significant difference was found between the control, LP-PRP, and LR-PRP groups. An inhibitory effect on cartilage degeneration was observed only in the pure-PRP group on day 14. Pure PRP also significantly inhibited expression of CGRP-positive nerve fibers in the infrapatellar fat pad compared with the other groups (P< .05). Conclusion: In an MIA-induced arthritis model, pure PRP injection was the most effective treatment for reduction of pain-related behavior and inhibition of synovial inflammation and pain sensitization.