Antinociceptive effect of Lecythis pisonis Camb. (Lecythidaceae) in models of acute pain in mice

Ethnopharmacological relevance

Lecythis pisonis Camb., also known in Brazil as sapucaia, is used in folk medicine against pruritus, muscle pain and gastric ulcer.

Aim of the study

To investigate the antinociceptive effect of ethanol extract from Lecythis pisonis leaves (LPEE), fractions (hexane-LPHF, ether-LPEF and ethyl acetate-LPEAF) and mixture of triterpenes [ursolic and oleanolic acids (MT)] in mice.

Materials and methods

LPEE and LPEF were evaluated on the acetic acid induced writhings and formalin, capsaicin and glutamate tests. In addition, MT was investigated on the writhings induced by acetic acid, capsaicin and glutamate tests. In the study of some possible mechanisms involved on the antinociceptive effect of LPEF, it was investigated the participation of opioid system, K⁺_ATP channels and l-arginine-nitric oxide pathway.

Results

LPEE (12.5 and 25 mg/kg, p.o.), LPEF and MT (6.25, 12.5 and 25 mg/kg, p.o.) reduced the writhings in comparison to saline. LPEE (100 mg/kg, p.o.) and LPEF (50 mg/kg, p.o.) were effective in inhibiting both phases of formalin test. In capsaicin test, LPEE (100 and 200 mg/kg, p.o.), LPEF (12.5–50 mg/kg, p.o) and MT (6.25–25 mg/kg, p.o.) showed a significant antinociceptive effect compared to the control. LPEE (25 and 50 mg/kg, p.o.), LPEF (50 and 100 mg/kg, p.o.) and MT (12.5 and 25 mg/kg, p.o.) reduced the glutamate-evoked nociceptive response. Treatment with naloxone, l-arginine and glibenclamide reversed the effect of LPEF in glutamate test.

Conclusions

These results indicate the antinociceptive effect of Lecythis pisonis leaves and suggest that this effect may be related to opioid pathway, K⁺_ATP channels, and l-arginine-nitric oxide modulation. Furthermore, these data support the ethnomedical use of this plant.     

Antinociceptive action of ethanolic extract obtained from roots of Humirianthera ampla Miers

Humirianthera ampla Miers is a member of the Icacinaceae family and presents great amounts of di and triterpenoids. These chemical constituents in roots of Humirianthera ampla sustain not only the ethnopharmacological use against snake venom, but also some anti-inflammatory and analgesic properties of the plant. In this study we investigated the antinociceptive action of the ethanolic extract (EE) from roots of the Humirianthera ampla in chemical and thermal models of pain in mice. The oral treatment with ethanolic extract dose-dependently inhibited glutamate-, capsaicin- and formalin-induced licking. However, it did not prevent the nociception caused by radiant heat on the tail-flick test. The ethanolic extract (30 mg/kg) caused marked inhibition of the nociceptive biting response induced by glutamate, (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD), N-methyl-d-aspartate (NMDA) and substance P. The antinociception caused by ethanolic extract was significantly attenuated by naloxone, l-arginine, WAY100635, ondansetron or ketanserin, but not by caffeine or naloxone methiodide. In conclusion, the ethanolic extract from roots of Humirianthera ampla produces antinociception against neurogenic and inflammatory models of nociception. The mechanisms of antinociception involve nitric oxide, opioid, serotonin and glutamate pathways. Therefore, our results support the ethnopharmacological use of the Humirianthera ampla against inflammatory and painful process caused by snake venom.     

Involvement of the L-arginine-nitric oxide pathway in the antinociception caused by fruits of Prosopis strombulifera (Lam.) Benth

Ethnopharmacological relevance

Prosopis strombulifera (Lam.) Benth. is a rhizomatous shrub that grows in the north and central zone of Argentina. In folk medicine, the fruits of this plant have been used as an astringent, anti-inflammatory and odontalgic agent and anti-diarrheic.

Aim of the study

To investigate the antinociceptive effect of ethanol (EE), chloroform (CE) and ethyl acetate (EtOAcE) extracts of Prosopis strombulifera fruits and the involvement of the l-arginine-nitric oxide pathway in this effect.

Materials and methods

The antinociceptive effects of the EE, CE and EtOAcE of Prosopis strombulifera fruits were evaluated in vivo using the formalin-induced pain test in mice with aspirin and morphine as reference antinociceptive compounds. The participation of the l-arginine-nitric oxide pathway in the antinociceptive effect was investigated in the same animal model using l-arginine as a nitric oxide (NO) precursor. The in vitro inhibitory effect of the extracts on LPS-induced nitric oxide production and iNOS expression was investigated in a J774A.1 macrophage-derived cell line.

Results

CE (300 mg/kg), in contrast to EE and EtOAcE, caused significant inhibition (p < 0.05) of the in vivo nociceptive response. Moreover, CE (100–1000 mg/kg, p.o.) produced a dose-dependent inhibition of the neurogenic and the inflammatory phases of the formalin test with inhibition values (at 600 mg/kg) of 42 ± 7% and 62 ± 7%, respectively. CE inhibition was more potent in the inflammatory phase, with an ID₅₀ of 400.1 (252.2–634.8) mg/kg. The antinociception caused by CE (600 mg/kg, p.o.) was significantly attenuated (p < 0.05) by i.p. treatment of mice with l-arginine (600 mg/kg). In addition, CE (100 μg/mL) produced significant in vitro inhibition (p < 0.001) of LPS-induced NO production, which was not observed with EE and EtOAcE at the same concentration. The inhibition of NO production by CE (10–100 μg/mL) was dose-dependent, with an IC₅₀ of 39.8 (34.4–46.1) μg/mL, and CE significantly inhibited LPS-induced iNOS expression in J774A.1 cells.

Conclusions

This study supports, in part, the ethnomedical use of Prosopis strombulifera fruits by showing that its CE produces moderate antinociception in vivo. The findings also provide scientific information for understanding the molecular mechanism involved in the analgesic effect of this plant.     

Sub-chronic inhibition of nitric-oxide synthesis modifies haloperidol-induced catalepsy and the number of NADPH-diaphorase neurons in mice

Rationale: N ^G-nitro-l-arginine (l-NOARG), an inhibitor of nitric-oxide synthase (NOS), induces catalepsy in mice. This effect undergoes rapid tolerance, showing a significant decrease after 2 days of sub-chronic l-NOARG treatment. Nitric oxide (NO) has been shown to influence dopaminergic neurotransmission in the striatum. Neuroleptic drugs such as haloperidol, which block dopamine receptors, also cause catalepsy in rodents. Objectives: To investigate the effects of sub-chronic l-NOARG treatment in haloperidol-induced catalepsy and the number of NOS neurons in areas related to motor control. Methods: Male albino Swiss mice were treated sub-chronically (twice a day for 4 days) with l-NOARG (40 mg/kg i.p.) or haloperidol (1 mg/kg i.p.). Catalepsy was evaluated at the beginning and the end of the treatments. Reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry was also employed to visualize NOS as an index of enzyme expression in mice brain regions related to motor control. Results: l-NOARG sub-chronic administration produced tolerance of l-NOARG and of haloperidol- induced catalepsy. It also induced an increase in the number of NADPH-d-positive cells in the dorsal part of the caudate and accumbens nuclei compared with haloperidol and in the pedunculopontine tegmental nucleus compared with saline. In contrast, there was a decrease in NADPH-d neuron number in the substantia nigra, pars compacta in both haloperidol-treated and l-NOARG-treated animals. Conclusions: The results give further support to the hypothesis that NO plays a role in motor behavior control and suggest that it may take part in the synaptic changes produced by antipsychotic treatment. Received: 23 February 1999 / Final version: 28 July 1999     

Nitric oxide in the amphibian (Ambystoma tigrinum) lateral line

Nicotinamide adenine dinucleotide phosphate reduced-diaphorase (NADPH-d) histochemistry was investigated in the axolotl (Ambystoma tigrinum) lateral line. Hair cells of neuromast organs of the head skin and neurons of the postotic ganglia showed a significant NADPH-d reaction. Multiunit recording of neuromast afferent activity was also performed. Nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) produced an initial slight excitation followed by a significant inhibition of the resting discharge of neuromast afferent neurons. In contrast N(G)-nitro-L-arginine (L-NOARG) produced non-significant actions on the afferent neurons discharge. These findings suggest that afferent neurons and hair cells of the lateral line produce nitric oxide that plays an active role in the mechanisms sustaining basal spike discharge in afferent neurons.