scholarly journals Comparison of morphine, oxycodone and the biased MOR agonist SR-17018 for tolerance and efficacy in mouse models of pain

2020 ◽  
Author(s):  
Fani Pantouli ◽  
Travis W. Grim ◽  
Cullen L. Schmid ◽  
Agnes Acevedo-Canabal ◽  
Nicole M. Kennedy ◽  
...  
Keyword(s):  
Repeated Administration ◽  
Spinal Reflex ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Pain Model ◽  
Thermal Nociception ◽  
Cellular Assays ◽  
Pain Models ◽  
Gtpγs Binding ◽  
Repeated Dosing

AbstractThe mu opioid receptor-selective agonist, SR-17018, preferentially activates GTPγS binding over βarrestin2 recruitment in cellular assays. In mice, SR-17018 stimulates GTPγS binding in brainstem and produces antinociception with potencies similar to morphine. However, it produces much less respiratory suppression and mice do not develop antinociceptive tolerance in the hot plate assay upon repeated dosing. Herein we evaluate the effects of acute and repeated dosing of SR-17018, oxycodone and morphine in additional models of pain-related behaviors. In the mouse warm water tail immersion assay, an assessment of spinal reflex to thermal nociception, repeated administration of SR-17018 produces tolerance as does morphine and oxycodone. SR-17018 retains efficacy in a formalin-induced inflammatory pain model upon repeated dosing, while oxycodone does not. In a chemotherapeutic-induced neuropathy pain model SR-17018 is more potent and efficacious than morphine or oxycodone, moreover, this efficacy is retained upon repeated dosing of SR-17018. These findings demonstrate that, with the exception of the tail flick test, SR-17018 retains efficacy upon chronic treatment across several pain models.

scholarly journals Co-administration of Pregabalin and Curcumin Synergistically Decreases Pain-Like Behaviors in Acute Nociceptive Pain Murine Models

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4172
Author(s):  
Sarinee Leksiri ◽  
Hasriadi Hasriadi ◽  
Peththa Wadu Dasuni Wasana ◽  
Opa Vajragupta ◽  
Pornchai Rojsitthisak ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Area Under The Curve ◽  
Synergistic Interaction ◽  
Nociceptive Pain ◽  
Fixed Dose ◽  
Tail Flick ◽  
Dose Ratio ◽  
Tail Flick Test ◽  
Analgesic Effects ◽  
Pain Models

Analgesic drugs in a combination-form can achieve greater efficacy with lesser side effects compared to either drug alone. The combination of drugs acting at different targets or mechanisms of action has been recognized as an alternative approach for achieving optimal analgesia. In this study, the analgesic effects of pregabalin (30, 60, 100, 200 mg/kg), curcumin (15, 30, 60, 100, 120 mg/kg), and 1:1 fixed-dose ratio of the pregabalin-curcumin combination were assessed using two acute nociceptive pain models, the acetic acid-induced writhing and tail-flick tests in mice. The pregabalin-curcumin combination produced a dose-dependent decrease in mean of writhes and an increase in the percentage of antinociception by the acetic acid-induced writhing test. In the tail-flick test, the combination also showed an improvement in antinociception indicated by the tail-flick latency, % antinociception, and area under the curve (AUC). Isobolographic analysis of interactions demonstrated a significant synergistic interaction effect between pregabalin and curcumin in both acute nociceptive pain models with the experimental ED50 below the predicted additive line and the combination index < 1. These findings demonstrate that the combination of pregabalin and curcumin exhibits a synergistic interaction in mouse models of acute nociceptive pain.

Antinociceptive Profiles of Platycodin D in the Mouse

2004 ◽  
Vol 32 (02) ◽  
pp. 257-268 ◽  
Author(s):  
Seong-Soo Choi ◽  
Eun-Jung Han ◽  
Tae-Hee Lee ◽  
Ki-Jung Han ◽  
Han-Kyu Lee ◽  
...  
Keyword(s):  
Antinociceptive Effect ◽  
Control Level ◽  
Tail Flick ◽  
Triterpene Saponins ◽  
Tail Flick Test ◽  
Platycodin D ◽  
Pain Models ◽  
Antinociceptive Effects ◽  
Dose Dependent ◽  
Higher Doses

Platycodin D (PD), one of several triterpene saponins, was isolated from roots of Platycodon grandiflorum. We previously reported that intracerebroventricular (i.c.v.) administration of PD showed an antinociceptive effect as measured by the tail-flick assay. However, its exact role in the regulation of antinociception in the various types of pain models has not yet been characterized. Thus, we attempted to find antinociceptive profiles of PD in various pain models. PD administered intraperitoneally (i.p.), i.c.v. or intrathecally (i.t.) showed antinociceptive effects in dose-dependent manners as measured by the tail-flick, writhing and formalin tests. In the tail-flick test, PD at the low doses reached the peak after 15 minutes and returned to the control level after 60 minutes. However, higher doses of PD showed a strong antinociception at least for 1 hour. PD administered i.t. showed stronger antinociception than that induced by i.c.v. administration PD in both tail-flick and writhing tests. In the formalin test, PD administered i.p., i.c.v. or i.t. showed antinociceptive effects during both the first (direct nociceptive stimulation) and second (late inflammatory) phases. Pretreatment with naltrexone i.p., i.c.v. or i.t. did not affect PD-induced inhibition of the tail-flick response. Our results suggest that PD shows a strong antinociceptive effect on the tail-flick, writhing and formalin tests, acting on central nervous system. However, PD-induced antinociception may not be mediated by the opioid receptors.

Nitric Oxide and Opioids Involvement in Isobolographic Nsaids Antinociception

Drug Research ◽  
2019 ◽  
Vol 69 (12) ◽  
pp. 688-694
Author(s):  
Hugo F. Miranda ◽  
Viviana Noriega ◽  
Fernando Sierralta ◽  
Paula Poblete ◽  
Nicolás Aranda ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mechanisms Of Action ◽  
Antinociceptive Activity ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Pain Model ◽  
Isobolographic Analysis

AbstractDifferent NSAIDs are used as antinociceptive in various analgesic assays, among which should be mentioned: ibuprofen, ketorolac , ketoprofen, meloxicam , paracetamol and others. It has been shown that NSAIDs possess antinociceptive activity by blocking cyclooxygenase enzymes (COXs). The present study was designed to evaluate the possible involvement of the nitridergic pathway due to L-NAME and the opioidergic route by NTX in the antinoception induced by NSAIDs using a murine pain model the tail flick test in an automatic tail flick algesiometer. The antinociception was evaluated by means of isobolographic analysis. The interaction between the combination of NSAIDs, via i.p., on basis of their ED25, demonstrated that the coadministration of the drugs were synergistic with the exception of the lack of effect in combination of meloxicam with ibuprofen and with ketorolac, since the result was additive. These data validate that the NSAIDs administered alone or in combinations produce antinociception in which other mechanisms of action must be added to the simple inhibition of COXs. In addition, the pretreatment of the mice with L-NAME and NTX does not change previous isobolographic parameters of the mixture of NSAIDs.

scholarly journals Analgesic and Antipyretic Activities of Methanol Extract and Its Fraction from the Root ofSchoenoplectus grossus

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Nirmal Kumar Subedi ◽  
S. M. Abdur Rahman ◽  
Mohammad Ahsanul Akbar
Keyword(s):  
Acetic Acid ◽  
Petroleum Ether ◽  
Methanol Extract ◽  
Diclofenac Sodium ◽  
Radiant Heat ◽  
Tail Flick ◽  
Dependent Manner ◽  
Tail Flick Test ◽  
Standard Drug ◽  
Pain Models

The study aims to evaluate analgesic and antipyretic activities of the methanol extract and its different fractions from root ofSchoenoplectus grossususing acetic acid induced writhing and radiant heat tail flick method of pain models in mice and yeast induced pyrexia in rats at the doses of 400 and 200 mg/kg. In acetic acid writhing test, the methanol extract, petroleum ether, and carbon tetrachloride fractions produced significant (P<0.001andP<0.05) inhibition of writhing responses in dose dependent manner. The methanol extract at 400 and 200 mg/kg being more protective with 54% and 45.45% of inhibition compared to diclofenac sodium of 56% followed by petroleum ether fractions of 49.69% and 39.39% at the same doses. The extracts did not produce any significant antinociceptive activity in tail flick test except standard morphine. When studied on yeast induced pyrexia, methanol and petroleum ether fractions significantly lowered the rectal temperature time dependently in a manner similar to standard drug paracetamol and distinctly more significant (P<0.001) after second hour. These findings suggest that the root extracts ofS. grossuspossess significant peripherally acting analgesic potential and antipyretic property. The phytochemical screening showed the presence of flavonoids, alkaloids, and tannins.

scholarly journals New ibuprofen derivatives with thiazolidine-4-one scaffold with improved pharmaco-toxicological profile

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ioana-Mirela Vasincu ◽  
Maria Apotrosoaei ◽  
Sandra Constantin ◽  
Maria Butnaru ◽  
Liliana Vereștiuc ◽  
...  
Keyword(s):  
Analgesic Effect ◽  
Visceral Pain ◽  
Biological Effects ◽  
Maximum Effect ◽  
Tail Flick ◽  
Paw Edema ◽  
Cell Viability Assay ◽  
Thermal Nociception ◽  
Analgesic Effects ◽  
Anti Inflammatory

Abstract Background Aryl-propionic acid derivatives with ibuprofen as representative drug are very important for therapy, being recommended especially for anti-inflammatory and analgesic effects. On other hand 1,3-thiazolidine-4-one scaffold is an important heterocycle, which is associated with different biological effects such as anti-inflammatory and analgesic, antioxidant, antiviral, antiproliferative, antimicrobial etc. The present study aimed to evaluated the toxicity degree and the anti-inflammatory and analgesic effects of new 1,3-thiazolidine-4-one derivatives of ibuprofen. Methods For evaluation the toxicity degree, cell viability assay using MTT method and acute toxicity assay on rats were applied. The carrageenan-induced paw-edema in rat was used for evaluation of the anti-inflammatory effect while for analgesic effect the tail-flick test, as thermal nociception in rats and the writhing assay, as visceral pain in mice, were used. Results The toxicological screening, in terms of cytotoxicity and toxicity degree on mice, revealed that the ibuprofen derivatives (4a-n) are non-cytotoxic at 2 μg/ml. In addition, ibuprofen derivatives reduced carrageenan-induced paw edema in rats, for most of them the maximum effect was recorded at 4 h after administration which means they have medium action latency, similar to that of ibuprofen. Moreover, for compound 4d the effect was higher than that of ibuprofen, even after 24 h of administration. The analgesic effect evaluation highlighted that 4 h showed increased pain inhibition in reference to ibuprofen in thermal (tail-flick assay) and visceral (writhing assay) nociception models. Conclusions The study revealed for ibuprofen derivatives, noted as 4 m, 4 k, 4e, 4d, a good anti-inflammatory and analgesic effect and also a safer profile compared with ibuprofen. These findings could suggest the promising potential use of them in the treatment of inflammatory pain conditions.

scholarly journals Effects of Electroacupuncture on Pain Threshold of Laboring Rats and the Expression of Norepinephrine Transporter andα2 Adrenergic Receptor in the Central Nervous System

2016 ◽  
Vol 2016 ◽  
pp. 1-8
Author(s):  
Qianli Tang ◽  
Qiuyan Jiang ◽  
Suren R. Sooranna ◽  
Shike Lin ◽  
Yuanyuan Feng ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adrenergic Receptor ◽  
Pain Threshold ◽  
Norepinephrine Transporter ◽  
Control Group ◽  
Tail Flick ◽  
Pregnant Rats ◽  
Tail Flick Test ◽  
The Central Nervous System

To observe the effects of electroacupuncture on pain threshold of laboring rats and the expression of norepinephrine transporter andα2 adrenergic receptor in the central nervous system to determine the mechanism of the analgesic effect of labor. 120 pregnant rats were divided into 6 groups: a control group, 4 electroacupuncture groups, and a meperidine group. After interventions, the warm water tail-flick test was used to observe pain threshold. NE levels in serum, NET, andα2AR mRNA and protein expression levels in the central nervous system were measured. No difference in pain threshold was observed between the 6 groups before intervention. After intervention, increased pain thresholds were observed in all groups except the control group with a higher threshold seen in the electroacupuncture groups. Serum NE levels decreased in the electroacupuncture and MP groups. Increases in NET andα2AR expression in the cerebral cortex and decreases in enlarged segments of the spinal cord were seen. Acupuncture increases uptake of NE via cerebral NET and decreases its uptake by spinal NET. The levels ofα2AR are also increased and decreased, respectively, in both tissues. This results in a decrease in systemic NE levels and may be the mechanism for its analgesic effects.

Mechanisms underlying antinociception provoked by heterosegmental noxious stimulation in the rat tail-flick test

Neuroscience ◽  
1995 ◽  
Vol 65 (1) ◽  
pp. 273-281 ◽  
Author(s):  
G.M. Pitcher ◽  
K. Yashpal ◽  
T.J. Coderre ◽  
J.L. Henry
Keyword(s):  
Tail Flick ◽  
Noxious Stimulation ◽  
Tail Flick Test ◽  
Rat Tail

Semi-synthesis of Novel Buprenorphine Derivatives and their Anti-nociceptive Properties and Dependency Potential

2021 ◽  
Author(s):  
Zahra Hasanpour ◽  
Peyman Salehi ◽  
Lennart Bunch ◽  
Mona Khoramjouy ◽  
Morteza Bararjanian ◽  
...  
Keyword(s):  
Opioid Receptors ◽  
Analgesic Effect ◽  
Preference Test ◽  
Biological Properties ◽  
Place Preference ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Active Compounds ◽  
Methyl Group ◽  
Analgesic Activities

Abstract: Novel 1,2,3-triazole-tethered N-norbuprenorphine derivatives with an OMe or OH group at the C3 position were synthesized alongside with evaluation of their analgesic properties. The analgesic activities of the resulting library were investigated via tail flick test in mice. Our results indicated that 10b and 10e were as effective as the starting compounds 8 and 9 with ED50 equal to 16.59 and 19.44 mg/kg, respectively. To investigate the effect of a methyl group at C3 on biological properties, the most active compounds were O-demethylated and their anti-nociceptive effects were assessed. The new O-demethylated derivatives (11b and 11e) showed better analgesic properties than the parent compounds with ED50 of 14.73 and 15.80 mg/kg, respectively. Naloxone prevented the analgesic effect of the synthesized compounds, indicating that the opioid receptors are highly involved in the anti-nociceptive effects of these. The potential dependency effects of the most potent derivatives were studied by condition place preference test in mice and compared to morphine and buprenorphine. Interestingly, 10b, 10e, 11b, and 11e did not show any dependency effect, similar to buprenorphine.

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