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Thalidomide potentiates analgesic effect of COX inhibitors on endotoxin‐induced hyperalgesia by modulating TNF‐α, PGE and NO synthesis in mice
Author(s) -
Buharalioglu Kemal,
Ozbasoglu Orcun,
Korkmaz Belma,
Cuez Tuba,
SahanFirat Seyhan,
Yalcin Atilla,
Tunctan Bahar
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.742.4
Subject(s) - hyperalgesia , nimesulide , nitric oxide , pharmacology , analgesic , chemistry , thalidomide , prostaglandin e , tumor necrosis factor alpha , cyclooxygenase , nitrite , prostaglandin , medicine , endocrinology , nociception , biochemistry , enzyme , receptor , organic chemistry , multiple myeloma , nitrate
Thalidomide has been shown to have both analgesic and antiinflammatory effects on the inflammatory pain through inhibition of TNF‐α, nitric oxide (NO) and prostanoid synthesis. Decreased production of NO associated with an increase in formation of prostaglandins (PGs) and TNF‐α contributes to endotoxin (ET)‐induced inflammatory hyperalgesia. We investigated whether thalidomide potentiates the analgesic effect of nonselective and selective cyclooxygenase (COX) inhibitors in ET‐induced hyperalgesia by modulating NO, TNF‐α and PGE synthesis on the hot plate response in mice. ET (10 mg/kg)‐induced hyperalgesia was associated with a decrease in serum and brain nitrite levels and an increase in serum TNF‐α and PGE levels. Thalidomide (0.5 mg/kg) opposed these effects of ET while indomethacin (1 mg/kg), paracetamol (0.1 mg/kg) and nimesulide (1 mg/kg) prevented the ET‐induced hyperalgesia and decrease in nitrite levels. Thalidomide not only decreased serum TNF‐α and PGE levels, and increased brain nitrite levels, but also potentiated the analgesic effect of the COX inhibitors in the ET‐treated mice. These data suggest that an increase in NO production associated with a decrease in TNF‐α and PGE synthesis contribute to the effect of thalidomide to prevent the ET‐induced hyperalgesia and potentiate the analgesic effect of COX inhibitors. This study was supported by Mersin University (BAP SBE EMB OÖ 2006‐3 YL).