Characterization of the acute and persistent pain state present in K/BxN serum transfer arthritis.
Characterization of the acute and persistent pain state present in K/BxN serum transfer arthritis.
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DOI：
10.1016/j.pain.2010.07.030
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发表时间：
2010-11
期刊：
影响因子：
7.4
通讯作者：
Svensson CI
中科院分区：
文献类型：
--
作者：
Christianson CA;Corr M;Firestein GS;Mobargha A;Yaksh TL;Svensson CI
类风湿关节炎（RA）是一种慢性自身免疫性关节炎，影响大约1%的人口。滑膜炎症不能完全解释患者报告的疼痛水平，并且涉及脊柱水平的疼痛处理便利化。我们将K/BxN血清转移关节炎模型定性为关节炎症性疼痛模型，并检查药理学反应性和脊髓胶质细胞激活。机械异常性痛的发生与关节肿胀一致。令人惊讶的是，异常性疼痛在炎症消退后仍然存在。在关节炎症的高峰期（第4-10天），服用依那西普、加巴喷丁和酮咯酸减轻了过敏反应。滑膜炎症消退后（第19-28天），只有加巴喷丁缓解了异常性疼痛。关节炎小鼠浅表背角小胶质细胞染色在早、晚时间点均增加，星形胶质细胞染色仅在炎症期增加。神经损伤标志物ATF3在大鼠腰背根神经节晚期（第28天）显著升高。因此，在K/BxN血清转移关节炎模型中，血清转移产生了持续的疼痛状态，炎症状态下的异位性疼痛被TNF和前列腺素抑制剂减轻，药理学和组织化学数据表明，随着时间的推移，炎症状态向类似神经性疾病的状态转变。因此，K/BxN血清转移模型为探索关节炎症条件下疼痛机制的研究提供了一个多方面的模型，并可作为探索人类关节炎疼痛新治疗策略的平台。K/BxN血清转移性关节炎产生持续的机械超敏反应，尽管临床症状有从炎症到神经性疼痛状态转变的证据。
Rheumatoid arthritis (RA) is a chronic autoimmune arthritis that affects approximately 1% of the population. Synovial inflammation cannot fully explain the level of pain reported by patients and facilitation of pain processing at the spinal level has been implicated. We characterized the K/BxN serum transfer arthritis model as a model of joint inflammation-induced pain and examine pharmacologic responsiveness and spinal glia activation. Mechanical allodynia developed congruently with joint swelling. Surprisingly, allodynia persisted after resolution of inflammation. At the peak of joint inflammation, (days 4–10) hypersensitivity was attenuated with i.p. etanercept, gabapentin, and ketorolac. Following resolution of synovial inflammation (day 19–28), only gabapentin relieved allodynia. The superficial dorsal horn of arthritic mice displayed increased staining of microglia at early and late time points, but astrocyte staining increased only during the inflammatory phase. ATF3, a marker of nerve injury, was significantly increased in the lumbar dorsal root ganglia during the late phase (day 28). Hence, serum transfer in the K/BxN serum transfer arthritis model produces a persistent pain state, where the allodynia during the inflammatory state is attenuated by TNF and prostaglandin inhibitors, and the pharmacology and histochemistry data suggest a transition from an inflammatory state to a state that resembles a neuropathic condition over time. Therefore, the K/BxN serum transfer model represents a multifaceted model for studies exploring pain mechanisms in conditions of joint inflammation and may serve as a platform for exploring novel treatment strategies for pain in human arthritic conditions. K/BxN serum transfer arthritis produces persistent mechanical hypersensitivity despite resolution of clinical signs with evidence of transition from an inflammatory to neuropathic pain state.
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