Zulkifal Malik1,2, Muzaffar Abbas2, Lina Tariq Al Kury3, Fawad Ali Shah1, Mahboob Alam2, Arif-Ullah Khan1, Humaira Nadeem1, Saad Alghamdi4, Muhammad Umar Khayam Sahibzada5, Shupeng Li6. 1. Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan. 2. Faculty of Pharmacy, Capital University of Science and Technology, Islamabad, Pakistan. 3. College of Natural and Health Sciences, Zayed University, Abu Dhabi, United Arab Emirates. 4. Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Mecca, Saudi Arabia. 5. Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, KPK, Pakistan. 6. State Key Laboratory of Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, People's Republic of China.
Abstract
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.
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.
Authors: Ian N Johnston; Erin D Milligan; Julie Wieseler-Frank; Matthew G Frank; Varlin Zapata; Jay Campisi; Stephen Langer; David Martin; Paula Green; M Fleshner; Leslie Leinwand; Steven F Maier; Linda R Watkins Journal: J Neurosci Date: 2004-08-18 Impact factor: 6.167
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Authors: Fernanda S Rodrigues; Mauren A Souza; Danieli V Magni; Ana Paula O Ferreira; Bibiana C Mota; Andreia M Cardoso; Mariana Paim; Léder L Xavier; Juliano Ferreira; Maria Rosa C Schetinger; Jaderson C Da Costa; Luiz Fernando F Royes; Michele R Fighera Journal: PLoS One Date: 2013-10-24 Impact factor: 3.240