Laboratory of Pathophysiology, Institute Butantan, São Paulo, Brazil.
J Thromb Haemost. 2011 Oct;9(10):2057-66. doi: 10.1111/j.1538-7836.2011.04449.x.
The role of platelets in hemostasis is well known, but few papers have reported their role in pain and edema induced by inflammatory agents.
To evaluate the role of circulating platelets in the local injury induced by two diverse inflammatory agents, Bothrops jararaca venom (Bjv) and carrageenan.
Rats were (i) rendered thrombocytopenic by administration of polyclonal anti-rat platelet IgG (ARPI) or busulfan, or (ii) treated with platelet inhibitors (aspirin or clopidogrel). Edema formation, local hemorrhage and the pain threshold were assessed after intraplantar injection of Bjv or carrageenan in rat hind paws. Additionally, whole platelets or platelet releasate were tested whether they directly induced hyperalgesia.
Platelet counts were markedly diminished in rats administered with either ARPI (± 88%) or busulfan (± 96%). Previous treatment with ARPI or busulfan slightly reduced edema induced by Bjv or carrageenan. Injection of Bjv, but not of carrageenan, induced a statistically significance increase in hemorrhage in the hind paws of thrombocytopenic rats. Remarkably, hyperalgesia evoked by Bjv or carrageenan was completely blocked in animals treated with ARPI or busulfan, or pre-treated with aspirin or clopidogrel. On the other hand, intraplantar administration of whole platelets or platelet releasate evoked hyperalgesia, which was inhibited by pre-incubation with alkaline phosphatase.
Thrombocytopenia or inhibition of platelet function drastically reduced hyperalgesia induced by injection of carrageenan or Bjv; moreover, platelets per se secrete phosphorylated compounds involved in pain mediation. Thus, blood platelets are crucial cells involved in the pain genesis, and their role therein has been underestimated.
血小板在止血中的作用众所周知，但很少有文献报道其在炎症介质引起的疼痛和水肿中的作用。
评估循环血小板在两种不同炎症介质（巴西矛头蝮蛇毒液（Bjv）和角叉菜胶）引起的局部损伤中的作用。
通过给予多克隆抗大鼠血小板 IgG（ARPI）或白消安使大鼠产生血小板减少症，或用血小板抑制剂（阿司匹林或氯吡格雷）治疗。在大鼠后爪皮内注射 Bjv 或角叉菜胶后，评估水肿形成、局部出血和痛阈。此外，还测试了全血小板或血小板释放物是否直接引起痛觉过敏。
给予 ARPI（±88%）或白消安（±96%）的大鼠血小板计数明显减少。ARPI 或白消安预处理轻微减少了 Bjv 或角叉菜胶引起的水肿。Bjv 注射，但不是角叉菜胶注射，导致血小板减少症大鼠后爪出血明显增加。值得注意的是，在 ARPI 或白消安预处理或预先用阿司匹林或氯吡格雷治疗的动物中，Bjv 或角叉菜胶引起的痛觉过敏完全被阻断。另一方面，全血小板或血小板释放物的皮内注射引起痛觉过敏，该痛觉过敏可被碱性磷酸酶预孵育抑制。
血小板减少症或血小板功能抑制可显著减少注射角叉菜胶或 Bjv 引起的痛觉过敏；此外，血小板本身分泌参与疼痛调节的磷酸化化合物。因此，血小板是参与疼痛发生的关键细胞，其作用被低估。
