Background: Peripheral inflammation leads to the development of persistent thermal hyperalgesia and mechanical allodynia associated with increased expression of interleukin-1β (IL-1β) in the spinal cord. The aim of the present study was to investigate the effects of thiazolidine derivatives, 1b ([2-(2-hydroxyphenyl)-1,3-thiazolidin-4-yl](morpholin-4-yl)methanone) and 1d (2-hydroxy-4-{[2-(2-hydroxyphenyl)-1,3-thiazolidine-4-carbonyl]amino}benzoic acid), on thermal hyperalgesia, mechanical allodynia and on IL-1β expression during carrageenan-induced inflammation in the spinal cord in mice. Inflammatory pain was induced by injecting 1% carrageenan into the right hind paw of the mice.
Methods: The animals were administered thiazolidine derivatives, 1b and 1d (1 mg/kg, 3 mg/kg, or 10 mg/kg), intraperitoneally 30 minutes before carrageenan administration. The animals’ behavior was evaluated by measuring thermal hyperalgesia, mechanical allodynia, and motor coordination. The IL-1β expression was measured by enzyme-linked immunosorbent assay. Acute and sub-acute toxicity studies were conducted to evaluate the toxicity profile of compounds.
Results: Treatment with the thiazolidine derivative, 1b and 1d, attenuated carrageenan-induced thermal hyperalgesia and mechanical allodynia at doses of 1 mg/kg, 3 mg/kg, and 10 mg/kg. No motor coordination deficits were observed in animals. The compounds also reduced IL-1β expression in the spinal cord of mice. Acute and sub-acute toxicity studies revealed that both compounds were safe.
Conclusion: The compounds exhibit promising activity against inflammatory pain due to their ability to produce anti-hyperalgesic and anti-allodynic effects and to inhibit IL-1β expression in the spinal cord.



中文翻译：

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噻唑烷衍生物减轻角叉菜胶引起的小鼠炎症性疼痛

背景：周围炎症导致持续性热痛觉过敏和机械性异常性疼痛，与脊髓中白细胞介素-1β (IL-1β) 表达增加相关。本研究的目的是研究噻唑烷衍生物 1b ([2-(2-羟基苯基)-1,3-噻唑烷-4-基](吗啉-4-基)甲酮) 和 1d (2-羟基-4-{[2-(2-羟基苯基)-1,3-噻唑烷-4-羰基]氨基}苯甲酸)，对角叉菜胶诱导的脊髓炎症期间的热痛觉过敏、机械异常性疼痛和 IL-1β 表达的影响小鼠体内的绳索。通过向小鼠右后爪注射1%角叉菜胶来诱发炎性疼痛。
方法：在施用角叉菜胶前30分钟，对动物腹膜内施用噻唑烷衍生物1b和1d（1mg/kg、3mg/kg或10mg/kg）。通过测量热痛觉过敏、机械异常性疼痛和运动协调来评估动物的行为。采用酶联免疫吸附法测定IL-1β的表达。进行急性和亚急性毒性研究以评估化合物的毒性特征。
结果：用噻唑烷衍生物1b和1d治疗，在1mg/kg、3mg/kg和10mg/kg剂量下减弱了角叉菜胶诱导的热痛觉过敏和机械异常性疼痛。在动物中没有观察到运动协调缺陷。这些化合物还降低了小鼠脊髓中 IL-1β 的表达。急性和亚急性毒性研究表明这两种化合物都是安全的。
结论：这些化合物由于能够产生抗痛觉过敏和抗异常性疼痛作用并抑制脊髓中 IL-1β 的表达，因此表现出有希望的抗炎性疼痛活性。