Distribution of ecto-nucleotidases in mouse sensory circuits suggests roles for nucleoside triphosphate diphosphohydrolase-3 in nociception and mechanoreception.

Nucleotide-activated P2X channels and P2Y metabotropic receptors participate in nociceptive signaling. Agonist availability is regulated by nucleoside triphosphate diphosphohydrolase-1 (NTPDase1), -2, -3, and -8, a family of enzymes that hydrolyze extracellular ATP to generate ADP (a P2Y agonist) and AMP. They provide a major source of extracellular AMP, the substrate for adenosine production by ecto-5'-nucleotidase (NT5E), and thereby regulate adenosine (P1) receptor signaling. NTPDases vary in their efficiency of tri- and diphosphate hydrolysis; therefore, which family members are expressed impacts nucleotide availability and half-life. This study employed enzyme activity histochemistry to examine the distribution of ATPase activity and immunohistochemistry for NTPDase1, 2, 3, and 8 in dorsal root ganglion (DRG) and spinal cord. Nucleotidase activity was robust in spinal dorsal horn, confirming that nociceptive pathways are a major site of nucleotide transmission. In DRG, extensive staining revealed ATPase activity in a subset of neurons and in non-neuronal cells. mRNA for NTPDase1-3, but not NTPDase8, was detected in lumbar DRG and spinal cord. Immunoreactivity for NTPDase3 closely matched the distribution of ATPase activity, labeling DRG central projections in the dorsal root and superficial dorsal horn, as well as intrinsic spinal neurons concentrated in lamina II. In DRG, NTPDase3 co-localized with markers of nociceptors and with NT5E. In addition, labeling of a subset of larger-diameter neurons in DRG was consistent with intense staining of Meissner corpuscle afferents in glabrous skin. Merkel cells and terminal Schwann cells of hair follicle afferents were also labeled, but the axons themselves were negative. We propose that NTPDase3 is a key regulator of nociceptive signaling that also makes an unexpected contribution to innocuous tactile sensation.

Pharmacological evidence favouring the use of Nauclea latifolia in malaria ethnopharmacy: effects against nociception, inflammation, and pyrexia in rats and mice.

AIM OF THE STUDY: Nauclea latifolia Smith is used traditionally in the treatment of uncomplicated malaria and painful conditions among its several other applications. The objective of this study is to investigate the pharmacological activities of the plant relevant to the symptomatic treatment of malaria fever and other painful conditions as an initial step towards developing an effective therapy for the symptomatic management of malaria fever and relief of other painful conditions. MATERIALS AND METHODS: Various concentrations of the aqueous extract of the root bark of this plant were evaluated for its anti-nociceptive, anti-inflammatory and anti-pyretic activities in mice and rats. Investigation of the anti-nociceptive activities was performed using the acetic acid-induced abdominal constriction and hot-plate tests in mice and formalin-induced pain test in rats, as models of nociception. The extract was also investigated for its effect against inflammation induced by egg-albumin and pyrexia induced by yeast in rats. RESULTS: Our data showed that the aqueous extract of Nauclea latifolia root bark (50-200mg/kg p.o.) significantly (P<0.05) attenuated writhing episodes induced by acetic acid and increased the threshold for pain perception in the hot-plate test in mice, dose-dependently. The product also remarkably decreased both the acute and delayed phases of formalin-induced pain in rats and also caused a significant reduction in both yeast-induced pyrexia and egg-albumin-induced oedema in rats. These effects were produced in a dose-dependent manner. CONCLUSION: The results suggest the presence of biologically active principles in the extract with anti-nociceptive, anti-inflammatory and anti-pyretic activities that justifies its use in malaria ethnopharmacy and subsequent development for clinical application.

Antinociceptive profile of the methanolic extract of Neorautanenia mitis root in rats and mice.

The antinociceptive activity of the methanolic extract of Neorautenania mitis was studied in mice and rats. Five experimental models of nociception employed were: acetic acid-induced abdominal constriction and hot-plate test in mice, formalin-induced pain, analgesy-meter and Randall-Selitto tests in rats. The antinociceptive action of the extract was tested against naloxone in the hot-plate test in a bid to further elucidate probable mechanisms of antinociception. Results showed that the extract at doses of 5, 10 and 20 mg/kg body weight caused significant (P<0.05) dose-dependent antinociceptive activity in all the nociceptive models. Naloxone (2 mg/kg), significantly (P<0.05) antagonised the antinociceptive activity at the highest dose of the extract (20 mg). The study showed that the methanolic extract of Neorautanenia mitis possesses both peripherally and centrally mediated antinociceptive activity. The peripherally mediated action may be linked partly to lipoxygenases and/or cyclo-oxygenases, while the central anti-nociception is likely to be mediated via opioid receptors in the CNS.

Anti-nociceptive and anti-inflammatory activities of the methanolic extract of Parinari polyandra stem bark in rats and mice.

The methanolic extract of the stem bark of Parinari polyandra (family Rosaceae) was investigated for possible anti-nociceptive and anti-inflammatory effects in mice and rats. Three models were used to study the extracts effects on nociception which were the acetic acid-induced abdominal constriction test, hot-plate method (both in mice) and the formalin test in rats. The anti-inflammatory effects were investigated employing the albumin-induced hind-paw oedema in rats. Results of the study revealed the extract to have significant (P<0.05) anti-nociceptive effect at a dose of 200 mg/kg p.o. in mice and rats in all the models for anti-nociception while 100 mg/kg p.o. showed significant (P<0.05) effect in the acetic acid-induced abdominal constriction test and in phase I of the formalin test. The extract also exhibited anti-inflammatory effects which were found to be significant (P<0.05) at 200 mg/kg p.o. in the rats tested. Preliminary phytochemical screening of the extract showed the presence of flavonoids, tannins, and saponin glycoside. The results suggest the extract contains pharmacologically active principles. The result is in agreement with the local application of the plant in painful and inflammatory conditions.

Postsynaptic dopamine (D(2))-mediated behavioural effects of high acute doses of artemisinin in rodents.

Artemisinin or qinghaosu is the active principle of quinghao (Artemisia annua L.) developed from Chinese traditional medicine, which is now widely used around the world against falciparum malaria. Behavioural effects of high acute doses of artemisinin were studied on spontaneous motor activity (SMA), exploratory behavior, apomorphine-induced stereotype behavior and pentobarbital sleeping time in mice and rats in order to provide additional evidence on its safety profile on the central nervous system (CNS). Effects of the drug on bromocriptine-induced hyperactivity in short term reserpinised mice were also evaluated. Intraperitoneal (i.p.) injection of artemisinin at doses of 50 and 100mg/kg, significantly (P<0.05) reduced the SMA in mice, prolonged the pentobarbital sleeping time in rats, and attenuated the apomorphine-induced stereotypy in mice. Mice pretreated with reserpine, showed a significant decrease in locomotor activity compared to the saline-treated group. Bromocriptine, a D(2) receptor agonist, induced locomotor activity in mice pretreated with reserpine which was attenuated by artemisinin. The results suggest that artemisinin possesses sedative property, which may be mediated via postsynaptic dopamine (D(2)) receptor in the CNS.

Effect of the aqueous extract of Chrysanthellum indicum on calcium mobilization and activation of rat portal vein.

The effects of the aqueous extract of Chrysanthellum indicum (CI) on calcium activation and mobilization were studied using the rat portal vein. The extract caused a concentration-dependent contraction of the portal vein. KCl (80 mM), norepinephrine (NA, 10(-6)M) and CI (4 mg/ml) evoked sustained contraction of the portal vein. In Ca-free medium (with EGTA) the contractions evoked by these agents were reduced significantly. The times-to-peak of KCl, NA and CI were similar -in normal PSS, but in Ca-free medium the times-to-peak for KCl and CI were greatly increased. The contractions induced by CI were not inhibited by chlorpropamide and prazosin, but were blocked by verapamil. The data obtained suggest that the aqueous extract of CI utilizes extracellular calcium pools to bring about contractile response and this effect might be mediated through the activation of potential-sensitive channels.

Central nervous system activity of the methanol extract of Ficus platyphylla stem bark.

The central nervous system (CNS) activity of the methanolic extract of Ficus platyphylla stem bark was studied on locomotor activity, pentobarbital sleeping time, exploratory behaviour, amphetamine-induced hyperactivity, apomorphine-induced stereotypy, active-avoidance and performance on tread mills (rota-rod), using mice and rats. The results revealed that the extract significantly reduced the locomotor and exploratory activities in mice, prolonged pentobarbital sleeping time in rats, attenuated amphetamine-induced hyperactivity and apomorphine-induced stereotypy in mice, dose-dependently. The extract significantly suppressed the active-avoidance response in rats, with no significant effect on motor co-ordination as determined by the performance on rota-rod. The results suggest that the extract may possess sedative principles with potential neuroleptic properties.

Pharmacological effects of the aqueous extract of Neorautanenia mitis in rodents.

The pharmacological effects of the aqueous extract of Neorautanenia mitis (family Papilonaceae) were studied in rodents. Investigations were carried out on acetic acid-induced writhing (pain) in mice and hind paw oedema in rats. The effects of the extract were also studied on the isolated non-pregnant rat uterus and rabbit jejunum. Results showed the extract to possess significant (P<0.05) dose-dependent anti-nociceptive activity between 12.5 and 50.0 mg/kg p.o. in mice and slight anti-inflammatory activity at 25 and 50 mg/kg p.o. in rats. The extract also produced a concentration-dependent inhibition of the normal rhythmic contraction of the isolated non-pregnant rat uterus. It was found to inhibit oxytocin-induced as well as acetylcholine-induced contractions in the rat uterus. The extract also exhibited concentration-dependent inhibition of spontaneous contractions of the rabbit jejunum. Preliminary phytochemical analysis of the extract revealed the presence of saponin glycosides, flavonoids, tannins and alkaloids. The extract had an intraperitoneal (i.p.) LD(50) of 282.84+/-3.2 mg/kg in mice. These data corroborate the traditional use of this plant in the treatment of dysmenorrhea.