Selective inhibition of adenylyl cyclase subtype 1 reduces inflammatory pain in chicken of gouty arthritis.
Selective inhibition of adenylyl cyclase subtype 1 reduces inflammatory pain in chicken of gouty arthritis.
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DOI：
10.1177/17448069211047863
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发表时间：
2021-01
期刊：
影响因子：
3.3
通讯作者：
Li XH
中科院分区：
文献类型：
--
作者：
Liu RH;Shi W;Zhang YX;Zhuo M;Li XH
尿酸酶缺乏导致人和家禽痛风的高发，这与啮齿类动物不同。因此，鸡被认为是研究痛风的理想动物模型之一。痛风相关的疼痛所造成的尿酸盐在关节中的积累是一种类型的炎性疼痛，它会导致关节功能的损害。我们以前的研究已经证明了钙刺激腺苷酸环化酶亚型1（AC 1）在啮齿类动物炎症性疼痛中的关键作用，但是，还没有在家禽中的研究。本研究采用鸡左踝关节注射尿酸单钠（mono-sodium urate，MSU）建立鸡痛风性关节炎模型，观察AC 1抑制剂NB 001对鸡痛风性关节炎的治疗作用。我们发现，MSU注射到鸡的左脚踝1-3小时后，成功地诱导了自发性疼痛行为，包括坐，单腿站立和跛行。此外，痛风性关节炎鸡的左踝关节也出现水肿和机械性疼痛超敏反应。经口给予NB 001后，痛风性关节炎鸡的自发痛行为和机械痛超敏反应均得到有效缓解。MSU诱导的鸡左踝水肿不受NB 001的影响，表明NB 001具有中枢作用。我们的研究结果提供了一个强有力的证据表明，AC 1参与调节家禽的炎性疼痛。选择性AC 1抑制剂NB 001对痛风疼痛产生镇痛作用（非抗炎作用），可用于人类和家禽痛风疼痛的未来治疗。
Lack of uricase leads to the high incidence of gout in humans and poultry, which is different from rodents. Therefore, chicken is considered to be one of the ideal animal models for the study of gout. Gout-related pain caused by the accumulation of urate in joints is one type of inflammatory pain, which causes damage to joint function. Our previous studies have demonstrated the crucial role of calcium-stimulated adenylyl cyclase subtype 1 (AC1) in inflammatory pain in rodents; however, there is no study in poultry. In the present study, we injected mono-sodium urate (MSU) into the left ankle joint of the chicken to establish a gouty arthritis model, and tested the effect of AC1 inhibitor NB001 on gouty arthritis in chickens. We found that MSU successfully induced spontaneous pain behaviors including sitting, standing on one leg, and limping after 1–3 h of injection into the left ankle of chickens. In addition, edema and mechanical pain hypersensitivity also occurred in the left ankle of chickens with gouty arthritis. After peroral administration of NB001 on chickens with gouty arthritis, both the spontaneous pain behaviors and the mechanical pain hypersensitivity were effectively relieved. The MSU-induced edema in the left ankle of chickens was not affected by NB001, suggesting a central effect of NB001. Our results provide a strong evidence that AC1 is involved in the regulation of inflammatory pain in poultry. A selective AC1 inhibitor NB001 produces an analgesic effect (not anti-inflammatory effect) on gouty pain and may be used for future treatment of gouty pain in both humans and poultry.
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DOI：
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发表时间：
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期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
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作者：
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