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Antinociceptive properties of esculetin in non‐inflammatory and inflammatory models of pain in rats
Author(s) -
Rzodkiewicz Przemyslaw,
Gasinska Emilia,
Maslinski Slawomir,
BujalskaZadrozny Magdalena
Publication year - 2015
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12346
Subject(s) - zileuton , pharmacology , analgesic , hyperalgesia , nociception , chemistry , carrageenan , arachidonate 5 lipoxygenase , anti inflammatory , medicine , threshold of pain , anesthesia , receptor , biochemistry , arachidonic acid , enzyme
Summary 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 B 4 ( LTB 4 ) 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 LTB 4 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.