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Background: Platycladus orientalis (L.) Franco (PO) has been used in Oriental medicine to treat rheumatism and diarrhea; however, its antinociceptive effects remain unclear. Objective: This study aimed to reveal the antinociceptive effect of the PO extract and standardize this extract in RAW 264.7 cells and mice with monosodium uric acid (MSU)-induced pain. Results: PO extracts were prepared using different ethanol (EtOH) concentrations (0–100%). Thereafter, groups were determined based on the results of the MSU-induced pain model in mice and nitric oxide (NO) assay using lipopolysaccharide (LPS)-induced RAW 264.7 cells. As the methylene chloride (CH2Cl2) and ethyl acetate (EtOAc) layers exhibited increasing effects with time, these layers were selected to isolate the major components. The PO extract was standardized using a highly efficient HPLC method, and its antinociceptive effects in a mouse model of MSU-induced gout pain were determined using the von Frey test. The PO extract was found to exhibit antinociceptive effects. Moreover, sample standardization was successfully achieved based on the validation of these compounds. Conclusion: The PO extract exhibited potent dose- and time-dependent antinociceptive effects in an animal model of gout pain; these effects might be mediated by the major compounds of this extract. Collectively, these results suggest that PO can be used as a herbal drug to treat gout-related pain. [ABSTRACT FROM AUTHOR]

Our previous research has shown that galanin plays an antinociceptive effect via binding to galanin receptors (GalRs) in nucleus accumbens (NAc). This study focused on the involvement of GalR2 in galanin-induced antinociceptive effect in NAc of neuropathic pain rats. The chronic constriction injury of sciatic nerve (CCI) was used to mimic neuropathic pain model. The hind paw withdrawal latency (HWL) to thermal stimulation and hind paw withdrawal threshold (HWT) to mechanical stimulation were measured as the indicators of pain threshold. The results showed that 14 and 28 days after CCI, the expression of GalR2 was up-regulated in bilateral NAc of rats, and intra-NAc injection of GalR2 antagonist M871 reversed galanin-induced increases in HWL and HWT of CCI rats. Furthermore, intra-NAc injection of GalR2 agonist M1145 induced increases in HWL and HWT at day 14 and day 28 after CCI, which could also be reversed by M871. Finally, we found that M1145-induced antinociceptive effect in NAc of CCI rats was stronger than that in intact rats. These results imply that the GalR2 is activated in the NAc from day 14 to day 28 after CCI and GalR2 is involved in the galanin-induced antinociceptive effect in NAc of CCI rats. [ABSTRACT FROM AUTHOR]

Achillea biebersteinii is a perennial aromatic herb that grows in the Mediterranean area. The leaves of this plant are used in foods as bittering and appetizing agents. In folk medicine, it is used for the treatment of stomachache and abdominal pain. In this study, the analgesic effect of A. biebersteinii methanolic flower extract was tested in three pain models, namely: writhing, tail-flick and paw-licking (formalin) tests. A. biebersteinii extract inhibited abdominal cramps produced by acetic acid. The effect of A. biebersteinii was better than that of 70 mg/kg indomethacin. In tail flick, A. biebersteinii extract increased latency at 30 min and was as effective as 100 mg/kg diclofenac sodium. In formalin test, A. biebersteinii extracts decreased paw-licking and flinching response in early and late phases. Atropine blocked the action of A. biebersteinii extract (300 mg/kg) in the late phase of formalin test as well as in writhing and tail-flick tests. GC–MS analysis revealed that ascaridole and iso-ascaridole were the main constituents of A. biebersteinii flower extract. In conclusion, this study shows for the first time that the antinociceptive effect of A. biebersteinii is mediated by the cholinergic receptor. [ABSTRACT FROM AUTHOR]

Botulinum toxin (BoTx) is a product of gram-positive anaerobic bacteria of the Clostridium genus. At present, seven serotypes (A to G) of BoTx have been identified. Each of them functions as a zincdependent endopeptidase that hydrolyzes peptide bonds within soluble N-ethylmaleimide-sensitive factor attaching protein receptors. BoTx affects proteins required for neurotransmitter release through presynaptic membranes. As a result, muscle weakness develops, or complete paralysis of the muscles occurs. These effects are not only limited to striated muscles but also may have impact on smooth muscles and secretory glands. The observation that BoTx can diffuse from the site of administration may indicate the possibility of direct or indirect influence of the toxin on the CNS. Consequently, the question arises: What is the mechanism of the central action of BoTx? Several mechanisms of such action have been proposed. However, recent findings showed that the most probable mechanism responsible for the central effects of BoTx action is its anterograde transport. In this review, we describe and discuss the most important aspects related to BoTx action on the CNS. [ABSTRACT FROM AUTHOR]

The antinociceptive activity of icariside E, a dihydrobenzofuran-type lignan isolated from Tabebuia roseo- alba (Ridley) Sandwith (Bignoniaceae) bark, was evaluated in mice by using chemical and thermal models of nociception. Intraperitoneal (i.p.) administration of crude T. roseo- alba bark extract and its methanol fraction inhibited acetic acid-induced abdominal constriction in mice. Furthermore, i.p. administration of 0.1, 1, and 10 mg/kg of icariside E reduced the number of writhes evoked by acetic acid injection by 46.9, 82.3, and 66.6 %, respectively. Icariside E administration had no effect in the first phase of the formalin test, but it reduced nociceptive behavior in the second phase as indicated by a reduction in the licking time. Icariside E did not modify thermal nociception in the hot-plate test model, suggesting that it had a peripheral antinociceptive action. The antinociceptive effect of icariside E in the writhing test was reversed by pre-administration of glibenclamide, but not of naloxone, atropine, yohimbine, or haloperidol. Together, these results indicated that the antinociceptive activity of icariside E from T. roseo- alba in models of chemical pain occurred through ATP-sensitive K channel-dependent mechanisms. [ABSTRACT FROM AUTHOR]

Background: The genus Ajuga is used for the treatment of joint pain, gout, and jaundice in traditional Iranian medicine (TIM). Ajuga chamaecistus ssp. tomentella is an exclusive subspecies of Ajuga chamaecistus in the flora of Iran. The aim of this study was to evaluate antinociceptive properties of some extracts from aerial parts of A. chamaecistus ssp. tomentella. Methods: Antinociceptive activities of total water and 80% methanol extracts, hexane, diethyl ether and n-butanolic partition fractions of the methanolic extract were analyzed using the formalin test in mice. Indomethacin (10 mg/kg) and normal saline were employed as positive and negative controls, respectively. Results: Oral administration of all extracts (200, 400 and 600 mg/kg) 30 min before formalin injection had no effect against the acute phase (0-5 min after formalin injection) of the formalin-induced licking time, but hexane fraction (200 mg/kg) caused a significant effect (p < 0.001) on the chronic phase (15-60 min after formalin injection). Total water and diethyl ether extracts at a dose of 400 mg/kg showed a very significant analgesic activity on the chronic phase (p< 0.001 and p < 0.01, respectively). Conclusions: The results of this study suggest that the extracts of A. chamaecistus ssp. tomentella have an analgesic property that supports traditional use of Ajuga genus for joint pain and other inflammatory diseases. [ABSTRACT FROM AUTHOR]

We studied the interaction of a single dose of different antidepressant medications with a single (acute) dose or implanted mini-pump (chronic) methadone administration in mice, using the hotplate assay. For the acute experiment, subthreshold doses of six antidepressant drugs were administered separately with a single dose of methadone. The addition of a subthreshold dose of desipramine or clomipramine to methadone produced significant augmentation of the methadone effect with each drug ( p < 0.05). Fluvoxamine given at a fixed subthreshold dose induced a synergistic effect only with a low methadone dose. Escitalopram, reboxetine and venlafaxine given separately, each at a fixed subthreshold dose, induced no interaction. Possible clinical implications of these findings are that while escitalopram, reboxetine and venlafaxine do not affect methadone's antinociception in mice and are safe to be given together with methadone when indicated, fluvoxamine, clomipramine and desipramine considerably augment methadone-induced effects and should be avoided in this population due to the risk of inducing opiate overdose. For the chromic experiment, when a subthreshold dose of either escitalopram, desipramine or clomipramine was injected to mice following 2 weeks of methadone administration with the mini-pump, none of the antidepressant drugs strengthened methadone's analgesic effect. Further studies are needed before possible clinical implications can be drawn. [ABSTRACT FROM AUTHOR]

In order to observe antinociceptive effect of Oxymatrine (OMT) and its effect on voltage-activated K channel, the acetic acid-induced abdominal contraction model of mouse was used to test the antinociceptive effect in vivo, and in vitro, the delayed rectifier K currents (Ik) in PC12 cells (rat pheochromocytoma cells) was recorded using the automated patch-clamp method. The results indicated that after application of OMT, the number of acetic acid-induced animal abdominal contraction was significantly decreased, Ik in PC12 cells was significantly decreased, and showed a concentration-dependent manner. After application of OMT, both the activation and inactivation curves of Ik of PC12 cells were shifted to negative potentials. This study revealed that OMT showed antinociceptive effect in mice. The inhibition of voltage-activated K channel might be one of mechanisms in which the enhanced both activation and inactivation of K channel were involved and might play important roles. [ABSTRACT FROM AUTHOR]

Lippia gracilis Schauer is an aromatic plant widely found in Northeastern Brazil. The leaf infusions or decoctions and alcoholic macerate are used for some inflammatory diseases and headache. This paper reports the isolation of naringenin by semi-preparative liquid chromatography from the methanolic extract of L. gracilis (ELg) and the evaluation of the analgesic and anti-inflammatory activities of this extract by measuring nociception through acetic acid, formalin, and hot-plate tests in carrageenan-induced inflammation in mice. Following oral administration, ELg (100, 200, and 400 mg/kg) significantly reduced the number of writhes in the writhing test and the time of paw licks in both phases of the formalin test when compared to the control group animals. Mice treated with ELg did not exhibit any behavioral alteration during the hot plate and rota-rod tests, suggesting non-participation of the supraspinal components in the modulation of pain by ELg and no motor abnormality. The oral administration of 400 mg/kg of ELg produced an anti-inflammatory effect on peritonitis induced by carrageenan. These effects can be associated with a decrease of inflammatory mediator synthesis by compounds of ELg, such as naringenin, which has anti-inflammatory action as already described. [ABSTRACT FROM AUTHOR]

In the present study, we attempted to elucidate the antinociceptive activity of Xylopia parviflora bark using the acetic acid-induced writhing test, hot plate test, and formalin test in mice. The MeOH extract (100 and 200 mg/kg, administered intraperitoneally (i.p.)) had an antinociceptive effect demonstrated by its inhibitory effects on writhing number induced by acetic acid. Three alkaloidal fractions exhibited significant antinociceptive effects in three animal models; the chloroform-soluble fraction, including secondary and tertiary alkaloids, exhibited the strongest effect. This result supported its use in folk medicine as an analgesic agent. We tested the main alkaloids of these fractions for their antinociceptive effects to clarify the active components. (+)-Corytuberine (6.3 and 12.5 mg/kg, i.p.) showed very strong activity, had a significant antinociceptive effect in the acetic acid-induced writhing test (with 49.4 and 98.9% reduction of writhes), in the hot plate test, and in the formalin test (with 55.4 and 90.6% inhibition during the first phase, and 73.9 and 99.9% during the second phase, respectively). (+)-Glaucine (12.5 and 25 mg/kg, i.p.) showed strong activity in three animal models, too. The activity of these compounds was also observed following oral administration in the acetic acid-induced writhing test. [ABSTRACT FROM AUTHOR]

Cannabidiol (CBD), a nonpsychoactive cannabinoid, was found to be converted to 9α-hydroxyhexahydrocannabinol (9α-OH-HHC) and 8-hydroxy- iso-hexahydrocannabinol (8-OH- iso-HHC) together with Δ9-tetrahydrocannabinol (Δ9-THC), a psychoactive cannabinoid, and cannabinol in artificial gastric juice. These cannabinoids were identified by gas chromatography-mass spectrometry (GC-MS) by comparison with the spectral data of the authentic compounds. Pharmacological effects of 9α-OH-HHC and 8-OH- iso-HHC in mice were examined using catalepsy, hypothermia, pentobarbital-induced sleep prolongation, and antinociception against acetic acid-induced writhing as indices. The ED50 values (effective dose producing a 50% reduction of control; mg/kg, i.v.) of 9α-OH-HHC and 8-OH- iso-HHC for the cataleptogenic effect were 8.0 and 30.4, respectively. 8-OH- iso-HHC (10 mg/kg, i.v.) produced a significant hypothermia from 15 to 90 min after administration, although 9α-OH-HHC failed to induce such an effect at the same dose. However, both HHCs (10 mg/kg, i.v.) significantly prolonged pentobarbital-induced sleeping time by 1.8 to 8.0 times as compared with the control solution with 1% Tween 80-saline. The ED50 values (mg/kg, i.v.) of 9α-OH-HHC and 8-OH- iso-HHC for the antinociceptive effect were 14.1 and 39.4, respectively. The present study demonstrated that CBD can be converted to Δ9-THC and its related cannabinoids, 9α-OH-HHC and 8-OH- iso-HHC, in artificial gastric juice, and that these HHCs show Δ9-THC-like effects in mice, although their pharmacological effects were less potent than those of Δ9-THC. [ABSTRACT FROM AUTHOR]

Nitrous oxide (N2O), or laughing gas, has been used for clinical anesthesia for more than a century and is still commonly used. While the anesthetic/hypnotic mechanisms of N2O remain largely unknown, the underlying mechanisms of its analgesic/antinociceptive effects have been elucidated during the last several decades. Evidence to date indicate that N2O induces opioid peptide release in the periaqueductal gray area of the midbrain leading to the activation of the descending inhibitory pathways, which results in modulation of the pain/nociceptive processing in the spinal cord. The types of opioid peptide induced by N2O and the subtypes of opioid receptors that mediate the antinociceptive effects of N2O appear to depend on various factors including the species and/or strain, the regions of the brain, and the paradigms of behavior testing used for the experiments. Among three types of descending inhibitory pathways, the descending noradrenergic inhibitory pathway seems to play the most prominent role. The specific elements involved are now being resolved. [ABSTRACT FROM AUTHOR]

The antinociceptive effect of Oxotremorine in mice was increased by tetrabenazine in the hot plate test. This effect of tetrabenazine was antagonized by desmethylimipramine and amphetamine, and enhanced by 5-hydroxytryptophan. Pretreatment with tetrabenazine prevented the increase in the level of acetylcholine in the brain induced by oxotremorine. There was no correlation between the antinociceptive effect and the acetylcholine concentration in the brain in animals treated with oxotremorine. It is suggested that in the enhancement of the antinociceptive effect of oxotremorine caused by tetrabenazine the depletion of catecholamines and not that of serotonin plays a predominant role. [ABSTRACT FROM AUTHOR]

The antinociceptive activity of morphine was determined in rats using the vocalisation test, whereby vocalisation was elicited by electrical stimulation of the tail. The effects of various drugs were compared with the corresponding changes in brain amine concentration. It is suggested that the antinociceptive activity of morphine as tested by this method depends on the concentration of CA in brain, NA being more important than DA. 5-HT does not seem to be involved. Apparently the antinociceptive effect of morphine does not follow a single mechanism since the putative transmitter substances play a different role depending on the animal species and test methods used. [ABSTRACT FROM AUTHOR]