The present study examined the antinociceptive effects of a hydroalcoholic extract of Polygala paniculata in chemical and thermal behavioural models of
pain in mice. The antinociceptive effects of hydroalcoholic extract was evaluated in chemical (
acetic-acid,
formalin,
capsaicin,
cinnamaldehyde and
glutamate tests) and thermal (tail-flick and hot-plate test) models of
pain or by biting behaviour following intratecal administration of both ionotropic and metabotropic agonists of
excitatory amino acids receptors glutamate and
cytokines such as
interleukin-1beta (IL-1beta) and tumour
necrosis factor-alpha (
TNF-alpha) in mice. When given orally, hydroalcoholic extract (0.001-10 mg/kg), produced potent and dose-dependent inhibition of
acetic acid-induced
visceral pain. In the
formalin test, the hydroalcoholic extract (0.0001-0.1 mg/kg orally) also caused significant inhibition of both the early (neurogenic
pain) and the late (inflammatory
pain) phases of
formalin-induced licking. However, it was more potent and efficacious in relation to the late phase of the
formalin test. The
capsaicin-induced nociception was also reduced at a dose of only 1.0 mg/kg orally. The hydroalcoholic extract significantly reduced the
cinnamaldehyde-induced nociception at doses of 0.01, 0.1 and 1.0 mg/kg orally. Moreover, the hydroalcoholic extract (0.001-1.0 mg/kg orally) caused significant and dose-dependent inhibition of
glutamate-induced
pain. However, only
rutin, but not
phebalosin or
aurapten, isolated from P. paniculata, administered intraperitoneally to mice, produced dose-related inhibition of
glutamate-induced
pain. Furthermore, the hydroalcoholic extract (0.1-100 mg/kg orally) had no effect in the tail-flick test. On the other hand, the hydroalcoholic extract caused a significant increase in the latency to response at a dose of 10 mg/kg orally, in the hot-plate test. The hydroalcoholic extract (0.1 mg/kg orally) antinociception, in the
glutamate test, was neither affected by intraperitoenal treatment of animals with
l-arginine (precursor of
nitric oxide, 600 mg/kg) and
naloxone (
opioid receptor antagonist, 1 mg/kg) nor associated with non-specific effects such as muscle relaxation or sedation. In addition,
oral administration of hydroalcoholic extract produced a great inhibition of the
pain-related behaviours induced by
intrathecal injection of
glutamate,
N-methyl-D-aspartate (
NMDA), IL-1beta and
TNF-alpha, but not by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic
acid (
AMPA),
kainate or trans-1-amino-1.3-cyclopentanediocarboxylic
acid (
trans-ACPD). Together, our results suggest that inhibition of glutamatergic ionotropic receptors, may account for the antinociceptive action reported for the hydroalcoholic extract from P. paniculata in models of chemical
pain used in this study.