title: Antinociceptive properties of esculetin in non-inflammatory and inflammatory models of pain in rats.
abstract: Some studies suggest that 5-lipoxygenase (5-LOX) inhibition or leukotriene receptor antagonism may effectively attenuate different kinds of pain. In the present study, we investigated whether esculetin (which, among other actions, potently inhibits 5-LOX) possesses analgesic activity in acute non-inflammatory pain and acute inflammatory pain models in rats. We also examined the effects of zileuton, a selective 5-LOX inhibitor, on esculetin activity. Plasma concentrations of leukotriene B4 (LTB4 ) after administration of esculetin were also determined. Esculetin (1.25-20 mg/kg, i.p.) dose-dependently alleviated hyperalgesia and exhibited antinociceptive effects in both experimental models. The greatest effect of esculetin was observed with a dose of 20 mg/kg. In carrageenan-induced inflammatory pain in rats, 20 mg/kg esculetin reversed or mitigated hyperalgesia, increasing the threshold to mechanical stimuli from a control value of -23.8 ± 1.8% to 15.2 ± 2.2% (P < 0.01) and that to thermal stimuli from -52.5 ± 6.1% to -9.5 ± 3.9% (P < 0.01). In non-inflammatory pain, after esculetin (20 mg/kg) administration the threshold values to mechanical and thermal stimuli increased to 75.9 ± 4.2% and 59.2 ± 4.3%, respectively (P < 0.01 for both). Zileuton (30 mg/kg, p.o.) alone slightly but significantly increased the pain threshold in the non-inflammatory and inflammatory acute pain models. Pretreatment with 30 mg/kg, p.o., zileuton significantly enhanced the analgesic activity of 5 mg/kg, i.p., esculetin in both pain models. Moreover, esculetin (10 mg/kg, i.p.) decreased LTB4 concentrations in the blood from 244 ± 29 pg/mL in the control group to 185 ± 11 pg/mL (P < 0.005). The results of the present study suggest the involvement of the 5-LOX pathway in esculetin analgesia.
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Rheumatology, Warsaw, Poland; Department of Pharmacodynamics, Centre for Preclinical Research and Technology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Rzodkiewicz
authors.forename: Emilia
authors.initials: E
authors.lastname: Gasinska
authors.forename: Slawomir
authors.initials: S
authors.lastname: Maslinski
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bujalska-Zadrozny
mesh_terms: D000698:Analgesia / Q000379:methods; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D004195:Disease Models, Animal; D006918:Hydroxyurea / Q000031:analogs & derivatives / Q000494:pharmacology; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism; D007249:Inflammation / Q000150:complications* / Q000378:metabolism; D007975:Leukotriene B4 / Q000097:blood; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000209:etiology*; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D014468:Umbelliferones / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D016859:Lipoxygenase Inhibitors; D014468:Umbelliferones; D007975:Leukotriene B4; D001094:Arachidonate 5-Lipoxygenase; C007628:esculetin; C063449:zileuton; D006918:Hydroxyurea
keywords: 5-lipoxygenase inhibitor; carrageenan; esculetin; hyperalgesia; pain; rat