This study was carried out in mice to determine the nonopioid receptor signaling pathway(s) that might modulate the antinociceptive activity of the aqueous and chloroform extracts of Muntingia calabura (M. calabura) leaves, using the hot-plate test. The leaves of M. calabura were sequentially soaked [1:2 (w/v); 72 h] in distilled water (dH(2)O) and chloroform. The 50% concentration extracts were selected for this study based on the plant's previously established antinociceptive profiles. The mice (n = 7) were pretreated (s.c.) for 10 min with the selected nonopioid receptor antagonists, followed by the (s.c.) administration of the respective extract. The latency of discomfort was recorded at the interval time of 0.5, 1, 2, 3, 4 and 5 h after the extract administration. The 5 mg/kg atropine, 10 mg/kg phenoxybenzamine, 10 mg/kg yohimbine, 10 mg/kg pindolol, 1 mg/kg haloperidol and 10 mg/kg bicuculline caused significant (p < 0.05) reduction in the aqueous extract-induced antinociceptive activity. The 10 mg/kg phenoxybenzamine, 10 mg/kg yohimbine, 10 mg/kg pindolol and 10 mg/kg bicuculline caused significant (p < 0.05) reduction in the chloroform extract-induced antinociceptive activity. In conclusion, the central antinociceptive activity of M. calabura leaves appears to be involved in the modulation of various nonopioid receptor signaling pathways. Its aqueous extract antinociceptive activity is mediated via modulation of the muscarinic, alpha(1)-adrenergic, alpha(2)-adrenergic, beta-adrenergic, dopaminergic and GABAergic receptors, while its chloroform extract activity is mediated via modulation of the alpha(1)-adrenergic, alpha(2)-adrenergic, beta-adrenergic and GABAergic receptors.

The ethanolic extract of Alpinia conchigera Griff. leaves (EACL) was evaluated for its antinociceptive and anti-inflammatory activities in several in vivo experimental models. Antinociceptive activity was determined using the acetic acid-induced abdominal writhing test, the hot plate test and the formalin test. Anti-inflammatory activity was determined using the carrageenan-induced paw edema test. The extract (30, 100 and 300 mg/kg i.p.) was found to possess significant, dose-dependent inhibitory activity in all test models. In addition, the antinociceptive effect of the extract in the acetic acid-induced writhing and hot plate tests was reversed by naloxone, suggesting that this activity is mediated through activation of the opioid system. These findings suggest that EACL presents notable analgesic and anti-inflammatory activities, which support its folkloric use for painful and inflammatory conditions.

Extracellular and whole-cell patch clamp intracellular recordings were made from rat medial vestibular nucleus (MVN) neurones in vitro, and their responses to selective mu-, kappa- and delta-opioid receptor agonists and antagonists were examined. Of 127 neurones tested, the large majority were inhibited in a dose-dependent manner by the delta-opioid receptor agonists [D-Ala2, D-Leu5]-enkephalin (DADLE) and [D-Pen2, Pen5]-enkephalin (DPLPE). The mu-opioid receptor agonist morphine and the kappa-receptor agonist U50,488 did not affect the tonic discharge rate of any of the 63 MVN cells tested. The delta-receptor antagonist naltrindole effectively antagonised the inhibitory effects of DADLE and DPLPE. Weak excitatory responses to high doses of DADLE were seen in only two MVN cells. These results demonstrate the presence of delta- but not mu- or kappa-opioid receptors on tonically active MVN neurones. Whole-cell intracellular recordings from MVN cells in a current clamp showed that the DADLE-induced inhibition was accompanied by membrane hyperpolarisation and decrease in input resistance, while voltage clamp experiments showed that DADLE induced an outward membrane current that was reduced but not abolished by 20 mM tetraethylammonium bromide. Thus the mechanisms of action of DADLE in inhibiting MVN cells involve the potentiation of outward K currents, in a similar way to the effects of opioids in other areas of brain. The inhibitory effects of DADLE increased linearly with age, so that the responses to DADLE in the youngest animals used here (60-80 g, approx. 3 weeks of age) were relatively small, increasing significantly over the following 2-3 weeks. This age-dependence may be due to post-natal changes in the density of delta-opiate receptors or the efficacy of the signalling pathways activated by them in the MVN cells over this time.