Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.
Faculty of Pharmacy, Capital University of Science and Technology, Islamabad, Pakistan.
Drug Des Devel Ther. 2021 Feb 4;15:369-384. doi: 10.2147/DDDT.S281559. eCollection 2021.
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-ylmethanone) 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.
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.
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.
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.
外周炎症导致持续的热痛觉过敏和机械性痛觉过敏的发展，伴随着脊髓中白细胞介素-1β（IL-1β）表达增加。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）对热痛觉过敏、机械性痛觉过敏和在小鼠脊髓中角叉菜胶诱导的炎症期间 IL-1β表达的影响。通过向小鼠右后爪注射 1%角叉菜胶诱导炎症性疼痛。
噻唑烷衍生物 1b 和 1d（1mg/kg、3mg/kg 或 10mg/kg）在角叉菜胶给药前 30 分钟腹腔内给药。通过测量热痛觉过敏、机械性痛觉过敏和运动协调来评估动物的行为。通过酶联免疫吸附试验测量 IL-1β表达。进行急性和亚急性毒性研究以评估化合物的毒性概况。
噻唑烷衍生物 1b 和 1d 的治疗减轻了 1mg/kg、3mg/kg 和 10mg/kg 剂量的角叉菜胶诱导的热痛觉过敏和机械性痛觉过敏。动物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。
这些化合物由于其产生抗痛觉过敏和抗痛觉过敏作用以及抑制脊髓中 IL-1β表达的能力，对炎症性疼痛表现出有希望的活性。
