There is strong evidence showing that the activation of peripheral proteinase-activated receptors type 2 (PAR-2) can initiate hyperalgesic and inflammatory responses in the joint. However, to date, there is no report of functional spinal PAR-2 receptors in arthritis models. The primary aim of this study was to evaluate the activity of PAR-2 receptors at the spinal cord by using a potent agonist (FLIGRL) in naïve animals, and an antagonist (GB83) in different models of joint pain. Saline or FLIGRL (10 nmol) were injected intrathecally in naïve animals and nociceptive behaviour was evaluated over a 24 h time period by von Frey hair algesiometry. Paw withdrawal threshold decreased from 3 to 24 h and this allodynic effect was blocked by GB83 (90 nmol; i.p.). Acute inflammatory joint pain was induced by injecting 0.5% kaolin/carrageenan (50 μL each) into the right knee joint of male Wistar rats (24 hr recovery). Chronic inflammatory joint pain was modelled by intraarticular injection of Freund’s complete adjuvant (FCA; 50 μL; 7 days recovery) or chronic osteoarthritis pain by sodium monoiodoacetate (MIA; 3 mg; 14 days recovery). Animals were then treated with either intrathecal vehicle or 10 nmol of GB83 (10 μL); joint pain was evaluated throughout the subsequent 3 h period. The acute inflammatory pain induced by kaolin/carrageenan was not affected by treatment with GB83. Conversely, both chronic arthritis models demonstrated increased hind paw withdrawal threshold after spinal injection of the PAR-2 antagonist. Based on these results, spinal PAR-2 receptors are involved in joint nociceptive processing in chronic but not acute arthritic conditions.

有强有力的证据表明，活化的2型外周蛋白酶激活受体（PAR-2）可以在关节中引发痛觉过敏和炎症反应。然而，迄今为止，在关节炎模型中尚无功能性脊柱PAR-2受体的报道。这项研究的主要目的是通过在幼稚动物中使用强效激动剂（FLIGRL）和在不同关节痛模型中使用拮抗剂（GB83）来评估脊髓PAR-2受体的活性。在幼稚动物的鞘内注射盐水或FLIGRL（10 nmol），并通过von Frey头发法进行24小时评估伤害行为。足爪退缩阈值从3小时降低到24小时，该止痛作用被GB83（90 nmol; ip）阻断。注射0可诱发急性炎症性关节痛。向雄性Wistar大鼠的右膝关节中注入5％高岭土/角叉菜胶（各50μL）（恢复24小时）。通过关节内注射弗氏完全佐剂（FCA； 50μL； 7天恢复）或通过单碘乙酸钠（MIA； 3 mg； 14天恢复）慢性骨关节炎疼痛来模拟慢性炎症性关节痛。然后用鞘内溶媒或10 nmol GB83（10μL）处理动物；在随后的3小时内评估关节疼痛。由高岭土/角叉菜胶诱导的急性炎性疼痛不受GB83治疗的影响。相反，两种慢性关节炎模型都证明脊柱注射PAR-2拮抗剂后后爪退缩阈值增加。基于这些结果，脊髓PAR-2受体在慢性而非急性关节炎条件下参与关节伤害性加工。