Research progress on anti-inflammatory and anti-tumor effects of sinomenine / 中国药理学通报

This review summarized some hot research fields in pharmacological effects of sinomenine such as anti-inflammatory, immunosuppressive, and anti-tumor effects. In addition to our exploration of its antinociceptive effect, we summarized above-mentioned pharmacological effects of sinomenine and its underly-ing mechanism, in order to provide an evidence for its clinical use.

Portulaca oleracea inhibit vincristine induced peripheral neuropathy: involvement of ATP-sensitive K+ channels.

Background: The Portulaca oleracea belonging to portulacaceae family. It is a herbaceous plant widely distributed throughout the world and used in traditional medicine for many ailments. The present study was to evaluate the antinociceptive action of petroleum ether extract of P. oleracea in vincristine induced peripheral neuropathic pain and the possible mechanisms involved. Methods: Peripheral neuropathy was induced in rats by administration of vincristine sulfate (50 μg/kg i.p.) for 10 consecutive days. The cold tail hyperalgesia was assessed by cold water tail immersion test. To identify the possible mechanisms involved in the antinociceptive action of petroleum ether extract of P. oleracea, acetic acid writhing method was employed. Mice were pretreated with naloxone, glibenclamide before petroleum ether extract treatment to identify the involvement of opioid and potassium channels, respectively. Results: The administration of petroleum ether extract of P. oleracea (100 and 200 mg/kg p.o.) for 10 days significantly attenuated vincristine-induced cold hyperalgesia. Pre-treatment with glibenclamide reversed the antinociceptive effect of P. oleracea, but the naloxone pre-treatment did not reverse the antinociceptive activity of P. oleracea. Conclusion: The results of the present study reveal the antinociceptive effect of P. oleracea in vincristine induced peripheral neuropathy and involving ATP-sensitive potassium channels pathway.

Leaf extract from Clusia nemorosa induces an antinociceptive effect in mice via a mechanism that is adrenergic systems dependent / 中国天然药物

Previous studies on the genus Clusia have shown anti-inflammatory and antiproliferative effects of the leaf extracts, but its antinociceptive activity has never been characterized. In the present study, the antinociceptive activity of the hexane extract of the leaves of Clusia nemorosa G. Mey, called HECn, was examined. Antinociceptive activity was evaluated using acetic acid-induced writhing, formalin, and hot-plate tests. All experiments were carried out on male Swiss mice. The extract (1-400 mg·kg(-1)), given by intraperitoneal route (i.p.) 1 h prior to testing, produced a dose-dependent inhibition on the number of abdominal writhings, with an ID50 of 62 mg·kg(-1). In addition, HECn was able to prevent the visceral pain induced by acetic acid in mice for at least 2 h. In the formalin test, HECn had no effect in the first phase, but produced an analgesic effect on the second phase with the inhibition of licking time. The HECn did not show a significant analgesic effect in the hot plate test. Pretreatment with yohimbine attenuated the antinociceptive effect induced by HECn in the writhing test. However, naloxone, atropine, or haloperidol did not affect antinociception induced by HECn in the writhing test. Together, these results indicate that the extract from the leaves of Clusia nemorosa produces antinociception in models of chemical pain through mechanisms that suggest participation of the adrenergic systems pathway.

Antinociceptive effects of gabapentin & its mechanism of action in experimental animal studies.

Background & objectives: Several studies have shown the possible analgesic effects of gabapentin, widely used as an antiepileptic. Thus, clinical studies have been carried out especially for neuropathic syndroms. This study was undertaken to investigate experimentally whether gabapentin has analgesic effects in mice and rats. Methods: The mice were divided into 10 groups (n=7) with various treatments to assess central and peripheral antinociceptive activity of gabapentin. Hot plate, tail clip and tail flick tests were applied for the investigation of central antinociceptive activity and the writhing test was applied for the investigation of peripheral antinociceptive activity. In addition, we also evaluated the levels of PGE2 and nNOS on perfused hippocampus slices of rats. Results: Gabapentin showed a peripheral antinociceptive effect at all doses and a central antinociceptive effect at 30mg/kg dose. While the L-NAME and cyproheptadine changed the central and peripheral effects of gabapentin, naloxone did not change these effects. In vitro studies showed that gabapentin significantly increased nNOS level. PGE2 and nNOS were found to have an important role in the antinociceptive effects of gabapentin at all doses and its combinations with L-NAME, cyproheptadine, indomethacine, and naloxone. As expected, PGE2 levels decreased in all groups, while nNOS levels increased, which is believed to be an adaptation mechanism. Interpretation & conclusions: Our findings indicate that arachidonate, nitrergic and serotonergic systems play an important role in the antinociceptive activity of gabapentin except for the opioidergic system. Additionally, this effect occured centrally and peripherally. These effects were also mediated by nNOS and PGE2.

Phytochemical screening, antinociceptive and anti-inflammatory activities of Chrysopogon zizanioides essential oil

Chrysopogon zizanioides (L.) Roberty, Poaceae, is a plant widely used in northeast Brazil in folk medicine for the treatment of various pathological conditions, including inflammatory pain. The present study evaluated the antinociceptive and anti-inflammatory effects of C. zizanioides essential oil (EO) in rodents. EO was further characterized by GC/MS. The major components of EO were identified as khusimol (19.57%), E-isovalencenol (13.24%), α-vetivone (5.25%), β-vetivone (4.87%) and hydroxy-valencene (4.64%). Following intraperitoneal injection (i.p.), EO at 50 and 100 mg/kg significantly reduced the number of writhes (51.9 and 64.9%, respectively) and the number of paw licks during phase 2 (56.7 and 86.2%, respectively) of a formalin model when compared to control group animals. However, EO-treated mice were ineffective at all doses in hot-plate and rota-rod tests. The EO inhibited the carrageenan-induced leukocyte migration to the peritoneal cavity in a dose-dependent manner (34.7, 35.4, and 62.5% at doses of 25, 50 and 100 mg/kg, respectively). In the paw edema test, the EO (100 mg/kg) inhibited all three phases of the edema equally well, suggesting that the EO has a non-selective inhibitory effect on the release or actions of these mediators. Our results suggest possible antinociceptive and anti-inflammatory effects of the EO.

Sertraline inhibits formalin-induced nociception and cardiovascular responses

The objective of the present study was to determine the antihyperalgesic effect of sertraline, measured indirectly by the changes of sciatic afferent nerve activity, and its effects on cardiorespiratory parameters, using the model of formalin-induced inflammatory nociception in anesthetized rats. Serum serotonin (5-HT) levels were measured in order to test their correlation with the analgesic effect. Male Wistar rats (250-300 g) were divided into 4 groups (N = 8/per group): sertraline-treated group (Sert + Saline (Sal) and Sert + Formalin (Form); 3 mg·kg-1·day-1, ip, for 7 days) and saline-treated group (Sal + Sal and Sal + Form). The rats were injected with 5 percent (50 µL) formalin or saline into the right hind paw. Sciatic nerve activity was recorded using a silver electrode connected to a NeuroLog apparatus, and cardiopulmonary parameters (mean arterial pressure, heart rate and respiratory frequency), assessed after arterial cannulation and tracheotomy, were monitored using a Data Acquisition System. Blood samples were collected from the animals and serum 5-HT levels were determined by ELISA. Formalin injection induced the following changes: sciatic afferent nerve activity (+50.8 ± 14.7 percent), mean arterial pressure (+1.4 ± 3 mmHg), heart rate (+13 ± 6.8 bpm), respiratory frequency (+4.6 ± 5 cpm) and serum 5-HT increased to 1162 ± 124.6 ng/mL. Treatment with sertraline significantly reduced all these parameters (respectively: +19.8 ± 6.9 percent, -3.3 ± 2 mmHg, -13.1 ± 10.8 bpm, -9.8 ± 5.7 cpm) and serum 5-HT level dropped to 634 ± 69 ng/mL (P < 0.05). These results suggest that sertraline plays an analgesic role in formalin-induced nociception probably through a serotonergic mechanism.

Botulinum toxin type-A effect as a preemptive treatment in a model of acute trigeminal pain: a pre-clinical double-blind and placebo-controlled study / Toxina botulínica do tipo-A no tratamento preemptivo da dor trigeminal aguda: estudo pré-clínico duplo cego placebo controlado

The purpose of this study was to investigate if botulinum neurotoxin type-A (BoNT/A) had a preemptive antinociceptive effect in a formalin-induced orofacial pain model (FT). To test this hypothesis, male Rattus norvegicus were injected with isotonic saline solution 0.9 percent or BoNT/A administered as a 40 μl bolus, lateral to their nose, at 24 hours, 8, 15, 22, 29 or 36 days pre-FT. The procedures were repeated 42 days later. Influence on motor activity was assessed through the open-field test. Pain scores corresponded to the time spent rubbing and flicking the injected area. Animals pre-treated with BoNT/A at the first protocol (8 days subgroup) showed reduced inflammatory scores (p=0.011). For the other groups no significant results were observed at any phase. Motor activity was similar in both groups. BoNT/A showed to be effective preventing inflammatory pain up to eight days after the first treatment, an effect not reproduced on the second dose administration.

O objetivo deste estudo foi investigar o efeito preemptivo da neurotoxina botulínica do tipo/A (NTBo/A) através de um modelo de dor orofacial induzida pelo teste da formalina (TF). Rattus norvegicus machos foram injetados no lábio superior com solução salina isotônica 0,9 por cento (SSI) ou NTBo/A (subgrupos 24 horas, 8, 15, 22, 29 ou 36 dias) antes do TF, em dois tratamentos farmacológicos e respectivas avaliações intercalados por 42 dias. Os escores da dor corresponderam ao tempo de fricção da região injetada. Após o primeiro pré-tratamento com NTBo/A no subgrupo 8 dias os escores da fase inflamatória foram menores do que no grupo SSI (p=0,011). Todas as outras comparações não foram significativas. Nos testes de atividade motora não ocorreram diferenças entre SSI e NTBo/A. A NTBo/A pode ser considerada como tratamento preemptivo das dores orofaciais quando utilizada até oito dias antes do estímulo álgico, não havendo consistência terapêutica após um segundo tratamento.

The Antinociceptive Effect of Intraperitoneally Administered Nonselective Nitric Oxide Synthase Inhibitor on the Rat Formalin Test / 대한통증학회지

BACKGROUND: Nitric oxide (NO) is involved in the transmission and modulation of nociceptive information at the peripheral, spinal cord and supraspinal levels. We conducted this experiment to assess the antinociceptive effects of a nonselective nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME), on the modulation of pain in rats subjected to the formalin test. METHODS: Formalin 5% was injected in the right hind paw after intraperitoneal (IP) injection of various doses of L-NAME (0.5 mg/kg, 1.5 mg/kg with and without L-arginine 100 mg/kg, 5.0 mg/kg). The number of flinches was measured. RESULTS: Formalin injected into the rat hind paw induced a biphasic nociceptive behavior. IP injected L-NAME diminished the nociceptive behaviors in a dose-dependent manner during phases 1 and 2. The concomitant injection of L-arginine reversed the antinocipetive effect of L-NAME. CONCLUSIONS: The data demonstrates that a nonselective NOS inhibitor, L-NAME, possesses antinociceptive properties in rats subjected to the formalin test, and the antinociceptive effect of L-NAME is reversed by the concomitant administration of L-arginine.

Effects of orphanin FQ on endomorphin-1 induced antinociception / 医学研究生学报

Objective: To observe the effects of OFQ on endomorphin-1 in pain modulation. Methods: OFQ and endomorphin-1 were microinjected intracerebroventricularly or intrathecally in rats. The pain thresholds were measured by tail-flick test and acetic-acid induced twitching test, and the changes of antinociceptive effects induced by endomorphin-1 were observed. Results: OFQ antagonizing endomorphin-1 antinociception at the supraspinal level, while enhancing at the spinal level were observed. Conclusion: OFQ has functional effects on endomorphin-1 in pain modulation,both in the brain and the spinal cord. The mechanisms of its effect may be different.

Cross-tolerance between orphanin FQ and morphine in rats / 第二军医大学学报

Objective:To assess whether intrathecal orphanin FQ can develop the antinociceptive effect tolerance,and whether there is a cross tolerance between the antinociceptive effect of intrathecal orphanin FQ and the ? opioid receptor agonist morphine.Methods: Tail flick test was used to observe the change of antinociceptive effect after orphanin FQ/morphine intrathecal microinjection into the rats tolerant to acute or chronic morphine/orphanin FQ.Results:Like morphine,large dosage of continuous intrathecal orphanin FQ microinjection produced tolerance to the antinociceptive effect,but there was no apparent cross tolerance between the orphanin FQ and morphine; Hyperalgesic response was found in morphine tolerant rats,but not in orphanin FQ tolerant rats.Conclusion:Lack of cross tolerance between the antinociceptive effect of intrathecal orphanin FQ and morphine indicates that the mechanism of tolerance to orphanin FQ may differ from that to morphine; The antinociceptive effect of intrathecal orphanin FQ may be largely related with its specific receptor in the spinal cord.

Effect of spinal substance P on the artinociceptive propoties of ketamine / 中国药理学通报

Aim To investigate the effect of spinal substance P on the antinociceptive propoties of ketamine. Methods Using behaviors and Fos expression technique,the effects of intrathecal administration (it) of substance P of different dose on the ketamine induced antinociception were observed in the formalin test of mice. Results Compared with NS group, the amount of time that mice spent licking the injected paw was dose-dependently decreased in 20 and 30 mg?kg -1 groups(P