Anti-hyperalgesic effect of an ethanolic extract of propolis in mice and rats

Propolis, or bee glue, which contains a complex mixture of secondary metabo lites, has long been used in many countries for the management of several d iseases. The purpose of this study was to evaluate, by means of several pha rmacological models, the anti-hyperalgesic effect of propolis collected in the south of Brazil. The abdominal constrictions induced in mice by intraperitoneal injection of acetic acid (0.6%), kaolin (50 mg kg(-1)) or zymosan (40 mg kg(-1)) were i nhibited to different extents by an extract of propolis (1-60 mg kg(-1)) ad ministered intraperitoneally 30 min earlier; mean ID50 (concentrations resu lting in 50% inhibition) values were 2.7, 10.8 and 10.7 mg kg(-1) respectiv ely, and maximum inhibition was 58+/-5, 57+/-10 and 51+/-5%, respectively. Given orally (25-200 mg kg(-1) Ih previously) propolis also inhibited the a bdominal constrictions induced by acetic acid (maximum inhibition 43+/-5%). When injected intraperitoneally (3-60 mg kg(-1), 30 min previously), propo lis attenuated both the neurogenic (first phase) and inflammatory (second p hase) pain responses and paw oedema caused by intraplantar injection of for malin (2.5%); maximum inhibition was 32+/-5, 43 +/- 6 and 19 +/- 2%, respec tively. Oral administration of propolis (25-200 mg kg(-1), 1h previously) i nhibited both phases and reduced the oedema formation associated with the s econd phase of the formalin test (maximum inhibition 22 +/- 5, 33 +/- 6 and 26 +/- 3%) and extract of propolis (3 -30 mg kg(-1) i.p. or 25 - 100 mg kg (-1) p.o., respectively 30 min and I h previously) significantly inhibited capsaicin-induced pain with maximum inhibition of 39 +/- 8 and 41 +/- 8%, r espectively. When assessed in the Randall-Sellito test of pain, the extract of propolis (3-30 mg kg(-1) i.p., 30min previously) significantly reversed the hyperalgesia induced by intraplantar injection of bradykinin (3 nmol p er paw) in rats (P < 0.01). In contrast with morphine the extract of propol is (less than or equal to 100 mg kg(-1), 30 min previously) was ineffective when assessed in the tail-flick and hot-plate thermal assays. Naloxone (5 mg kg(-1) i.p.) reversed (P < 0.01) the effect of morphine (5 mg kg(-1) s.c .) by 70 and 94% respectively in the first and second phases of the formali n test, but did not interfere with the analgesic effect of propolis (10 mg kg(-1) i.p., 30 min previously). These results show that ethanolic extract of propolis, given systemically, has significant anti-hyperalgesic action when assessed in chemical, but not thermal, models of nociception in mice and rats. Its analgesic action seem s to be unrelated to release or activation of the opioid system.