Contribution of spinal 5-HT5A receptors to the antinociceptive effects of systemically administered cannabinoid agonist WIN 55,212-2 and morphine

2018 ◽  
Vol 96 (6) ◽  
pp. 618-623 ◽  
Author(s):  
Ahmet Goktan Aksu ◽  
Ozgur Gunduz ◽  
Ahmet Ulugol
Keyword(s):  
Receptor Antagonist ◽  
Motor Coordination ◽  
Antinociceptive Effect ◽  
Antinociceptive Activity ◽  
Tail Flick ◽  
Hot Plate ◽  
Rotarod Test ◽  
Antinociceptive Effects ◽  
Cb2 Agonist ◽  
Cannabinoid Agonist

The antinociceptive effects of cannabinoids and opioids have been known for centuries. Serotonin and its receptors are also known to play important roles in nociception. However, the contribution of spinal 5-HT5A receptors in antinociceptive effects of cannabinoids and opioids has not been studied. We conducted this study to clarify spinal mechanisms of the actions of the antinociceptive effects of cannabinoids and opioids. Hot plate and tail flick tests were used to assess the antinociceptive activity in Balb/c mice. WIN 55,212-2, a nonselective CB1 and CB2 agonist, and morphine exerted significant antinociceptive effects at 1, 3, and 10 mg/kg doses administered intraperitoneally in both hot plate and tail flick tests. The selective 5-HT5A receptor antagonist SB-699551 (10 nmol/mouse) was administered intrathecally 10 min before the agonists. SB-699551 significantly reduced the antinociceptive effect of both WIN 55,212-2 and morphine. In the rotarod test, WIN 55,212-2 disrupted the motor coordination at a dose of 10 mg/kg, while morphine did not affect this function at any dose. Our findings show that spinal 5-HT5A receptors are involved in the antinociceptive effects of WIN 55,212-2 and morphine.

scholarly journals Comparison of antinociceptive effect of the antiepileptic drug gabapentin to that of various dosage combinations of gabapentin with lamotrigine and topiramate in mice and rats

2011 ◽  
Vol 02 (02) ◽  
pp. 130-136 ◽  
Author(s):  
Keshab Raj Paudel ◽  
SK Bhattacharya ◽  
GP Rauniar ◽  
BP Das
Keyword(s):  
Pain Perception ◽  
Late Phase ◽  
Antinociceptive Effect ◽  
Experimental Pain ◽  
Mechanical Hyperalgesia ◽  
Tail Flick ◽  
Hot Plate ◽  
Analgesic Effects ◽  
Pain Models ◽  
Antinociceptive Effects

ABSTRACT Introduction: Newer anticonvulsants have a neuromodulatory effect on pain perception mechanisms in a hyperexcitable and damaged nervous system. Aim: This study was designed to study the analgesic effects of gabapentin alone and in combination with lamotrigine and topiramate in experimental pain models. Materials and Methods: Adult albino mice (n = 490) weighing 20–30 g and rats (n = 130) weighing 100–200 g were injected intraperitoneally with gabapentin, lamotrigine, and topiramate alone and in different dose combinations. The hot-plate method, tail-flick method, capsaicin-induced mechanical hyperalgesia, and formalin assay were used to assess the antinociceptive effects. Results: Of the three antiepileptic drugs, when given separately, gabapentin was more efficacious than either topiramate or lamotrigine in all the pain models. Combination of 25 mg/kg gabapentin with 25 mg/kg topiramate was more efficacious (P <.05) than 50 mg/kg gabapentin alone in the capsaicin-induced mechanical hyperalgesia test. Similarly, 50 mg/kg gabapentin with 50 mg/kg topiramate or 5 mg/kg lamotrigine was more efficacious (P <.05) than 50 or 100 mg/kg gabapentin alone in late-phase formalin-induced behaviors. Conclusions: Combination of gabapentin with either lamotrigine or topiramate produced better results than gabapentin alone in capsaicin-induced mechanical hyperalgesia test and in late-phase formalin-induced behaviors.

The mineralocorticoid receptor antagonist spironolactone enhances morphine antinociception

2013 ◽  
Vol 4 (4) ◽  
pp. 259-259
Author(s):  
Viljami Jokinen ◽  
Tuomas O. Lilius ◽  
Mikko S. Neuvonen ◽  
Antti J. Väänänen ◽  
Mikko O. Niemi ◽  
...  
Keyword(s):  
Antinociceptive Effect ◽  
Morphine Tolerance ◽  
Tail Flick ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Mineralocorticoid Receptor Antagonist ◽  
P Glycoprotein ◽  
Antinociceptive Effects ◽  
The Brain ◽  
Glycoprotein Inhibition

Abstract Aims Spironolactone, an antimineralocorticoid, has been reported to potentiate the cataleptic effect of morphine in the rat. Since no previous research exists on the matter and the interaction might be clinically significant, the effects of spironolactone on morphine antinociception and pharmacokinetics in the rat were investigated. Methods Male SD rats were used to assess the effects of spironolactone on acute morphine-induced antinociception, development of morphine tolerance, and established morphine tolerance in the tail-flick and hot plate tests. Spironolactone was also administered with loperamide to assess whether spironolactone enhances the brain distribution of the acknowledged P-glycoprotein substrate across the blood-brain barrier. Results Spironolactone had no antinociceptive effects of its own but when co-administrated with morphine the antinociceptive effect of morphine was greatly enhanced. Morphine concentrations in the brain were increased fourfold in the spironolactone co-administrated group. Spironolactone did not inhibit the formation of pro-nociceptive morphine-3-glucuronide, nor did inhibit the development of tolerance. The peripherally restricted opioid, loperamide, had no antinociceptive effects by itself, but co-administration with spironolactone produced a clear change in the hot plate test. Conclusions Although mineralocorticoids have been proposed to take part in pain signaling, in our setting spironolactone did not have antinociceptive properties of its own. The increased antinociceptive effect of morphine is apparently caused by the increased morphine brain concentrations. We suggest this to be due to P-glycoprotein inhibition, as indicated by the loperamide assay. The clinical relevance of P-glycoprotein inhibition by spironolactone should be studied.

scholarly journals Two New βN-Alkanoyl-5-Hydroxytryptamides with Relevant Antinociceptive Activity

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 455
Author(s):  
Jorge Luis Amorim ◽  
Fernanda Alves Lima ◽  
Ana Laura Macedo Brand ◽  
Silvio Cunha ◽  
Claudia Moraes Rezende ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Antinociceptive Activity ◽  
Heated Plate ◽  
Plate Model ◽  
Cannabinoid Cb1 Receptor ◽  
Hot Plate ◽  
Antinociceptive Effects ◽  
New Compounds ◽  
Induced Reaction ◽  
Serotoninergic Receptor

In this work, we describe a new route for the synthesis and the antinociceptive effects of two new βN-alkanoyl-5-hydroxytryptamides (named C20:0-5HT and C22:0-5HT). The antinociceptive activities were evaluated using well-known models of thermal-induced (reaction to a heated plate, the hot plate model) or chemical-induced (licking response to paw injection of formalin, capsaicin, or glutamate) nociception. The mechanism of action for C20:0-5HT and C22:0-5HT was evaluated using naloxone (opioid receptor antagonist, 1 mg/kg), atropine (muscarinic receptor antagonist, 1 mg/kg), AM251 (cannabinoid CB1 receptor antagonist, 1 mg/kg), or ondansetron (5-HT3 serotoninergic receptor antagonist, 0.5 mg/kg) 30 min prior to C20:0-5HT or C22:0-5HT. The substances both presented significant effects by reducing licking behavior induced by formalin, capsaicin, and glutamate and increasing the latency time in the hot plate model. Opioidergic, muscarinic, cannabinoid, and serotoninergic pathways seem to be involved in the antinociceptive activity since their antagonists reversed the observed effect. Opioid receptors are partially involved due to tolerant mice demonstrating less antinociception when treated with both compounds. Our data showed a quicker and simpler route for the synthesis of the new βN-alkanoyl-5-hydroxytryptamides. Both compounds demonstrated significant antinociceptive effects. These new compounds could be used as a scaffold for the synthesis of analogues with promising antinociceptive effects.

scholarly journals Antinociceptive effects of intraperitoneal citicoline administration on rat models of acute pain

2018 ◽  
pp. 98-100
Author(s):  
Л.В. Кузнецова ◽  
М.Н. Карпова ◽  
Н.В. Клишина ◽  
М.Л. Кукушкин
Keyword(s):  
Acute Pain ◽  
Wistar Rats ◽  
Pain Sensitivity ◽  
Antinociceptive Effect ◽  
Tail Flick ◽  
Hot Plate ◽  
Antinociceptive Effects ◽  
Series Of Experiments ◽  
Dose Dependent ◽  
Dose Dependent Effect

Цель исследования - изучение дозозависимого эффекта мультимодального препарата цитиколина на моделях острой боли у крыс линии Вистар. Методы. Оценку изменения индивидуальной болевой чувствительности у животных проводили с помощью 2 стандартных тестов: «Tail flick» и «Hot plate». Проведено 2 серии опытов. В 1-й и 2-й сериях опытов определяли пороги болевой чувствительности (ПБЧ) у животных до и через 1 час после внутрибрюшинного введения цитиколина в дозах 500 и 1000 мг/кг. Результаты. Введение цитиколин в дозе 500 мг/кг оказывает антиноцицептивное действие: ПБЧ повышался по тестам Hot рlate и Hot рlate. Увеличение дозы цитиколина до 1000 мг/кг не оказывало более выраженного антиноцицептивного действия. Заключение. Введение цитиколина оказывает антиноцицептивные эффекты у крыс, что может свидетельствовать о холинергической активации, индуцированной цитиколином. The aim was to study the dose-dependent effect of the multimodal drug citicoline on models of acute pain in Wistar rats. Methods. Assessment of changes in individual pain sensitivity was performed using 2 standard tests, Tail Flick and Hot Plate. Two series of experiments were carried out. In the 1st and 2nd series of experiments, pain thresholds (PS) were determined prior to and one hour after intraperitoneal citicoline administration at doses of 500 and 1000 mg/kg. Results. Administration of citicoline 500 mg/kg had an antinociceptive effect: PS increased both in the Tail Flick and in the Hot Plate tests. Increasing the citicoline dose to 1000 mg/kg did not exert a more pronounced antinociceptive effect. Conclusion. Citicoline exerts antinociceptive effects in rats, which may indicate the cholinergic activation induced by citicoline.

scholarly journals Aristolochia trilobata: Identification of the Anti-Inflammatory and Antinociceptive Effects

Biomedicines ◽  
2020 ◽  
Vol 8 (5) ◽  
pp. 111
Author(s):  
Dayana da Costa Salomé ◽  
Natália de Morais Cordeiro ◽  
Tayná Sequeira Valério ◽  
Darlisson de Alexandria Santos ◽  
Péricles Barreto Alves ◽  
...  
Keyword(s):  
Enzyme Inhibitor ◽  
Interleukin 1 ◽  
Antinociceptive Effect ◽  
Cholinergic Receptor ◽  
Hot Plate ◽  
Nitric Oxide Synthase Inhibitor ◽  
Antinociceptive Effects ◽  
Anti Inflammatory ◽  
Skin Affection ◽  
Synthase Inhibitor

Aristolochia trilobata, popularly known as “mil-homens,” is widely used for treatment of stomach aches, colic, asthma, pulmonary diseases, diabetes, and skin affection. We evaluated the antinociceptive and anti-inflammatory activities of the essential oil (EO) and the main constituent, 6-methyl-5-hepten-2-yl acetate (sulcatyl acetate, SA). EO and SA (1, 10, and 100 mg/kg, p.o.) were evaluated using chemical (formalin-induced licking) and thermal (hot-plate) models of nociception or inflammation (carrageenan-induced cell migration into the subcutaneous air pouch, SAP). The mechanism of antinociceptive activity was evaluated using opioid, cholinergic receptor antagonists (naloxone and atropine), or nitric oxide synthase inhibitor (L-NAME). EO and SA presented a central antinociceptive effect (the hot-plate model). In formalin-induced licking response, higher doses of EO and SA also reduced 1st and 2nd phases. None of the antagonists and enzyme inhibitor reversed antinociceptive effects. EO and SA reduced the leukocyte migration into the SAP, and the cytokines tumor necrosis factor and interleukin-1 (TNF-α and IL-1β, respectively) produced in the exudate. Our results are indicative that EO and SA present peripheral and central antinociceptive and anti-inflammatory effects.

scholarly journals Comparing the Antinociceptive Effects of Methamphetamine, Buprenorphine, or Both After Chronic Treatment and Withdrawal in Male Rats

2019 ◽  
Vol 10 (4) ◽  
pp. 313-322
Author(s):  
Farshid Etaee ◽  
◽  
Arezoo Rezvani-Kamran ◽  
Mohammad Taheri ◽  
Ghazaleh Omidi ◽  
...  
Keyword(s):  
Pain Perception ◽  
Synergistic Effects ◽  
Reaction Times ◽  
Male Rats ◽  
Tail Flick ◽  
Hot Plate ◽  
Analgesic Effects ◽  
Antinociceptive Effects ◽  
Male Wistar Rats ◽  
Post Hoc

Introduction: Methamphetamine (Meth) and Buprenorphine (BUP) modulate pain perception. However, the antinociceptive effects of their interactions, which affect through different systems, are unclear in rats. This study aimed to compare the analgesic effects of Meth, BUP, and their coadministration, as well as the effect of withdrawal from these substances on nociception in male rats. Methods: In this experiment, 40 male Wistar rats (weight: 250-300 g) were categorized into four groups: control, Meth, BUP, or BUP+Meth. After seven days of treatments, the antinociceptive effects were assessed using the hot plate and the tail flick tests. The differences among the groups were analyzed with ANOVA and Tukey’s post hoc tests. P values less than 0.05 were considered significant. Results: Meth and BUP increased the reaction times during the hot plate and tail flick tests. The combination of Meth and BUP increased reaction time more than Meth or BUP alone.  Conclusion: The significantly high reaction times in rats treated with Meth and BUP indicate that these substances have antinociceptive effects. In addition, Meth enhanced the antinociceptive effects of BUP. These synergistic effects might occur through the dopaminergic, serotonergic, and or adrenergic systems.

scholarly journals Borneol, a Bicyclic Monoterpene Alcohol, Reduces Nociceptive Behavior and Inflammatory Response in Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Jackson Roberto Guedes da Silva Almeida ◽  
Grasielly Rocha Souza ◽  
Juliane Cabral Silva ◽  
Sarah Raquel Gomes de Lima Saraiva ◽  
Raimundo Gonçalves de Oliveira Júnior ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Motor Coordination ◽  
Nociceptive Behavior ◽  
Hot Plate ◽  
Rotarod Test ◽  
Hot Plate Test ◽  
Plate Test ◽  
Strength Tests ◽  
Anti Inflammatory ◽  
Motor Abnormality

Borneol, a bicyclic monoterpene, has been evaluated for antinociceptive and anti-inflammatory activities. Antinociceptive and anti-inflammatory activities were studied by measuring nociception by acetic acid, formalin, hot plate, and grip strength tests, while inflammation was prompted by carrageenan-induced peritonitis. The rotarod test was used to evaluate motor coordination. Borneol produced a significant (P<0.01) reduction of the nociceptive behavior at the early and late phases of paw licking and reduced the writhing reflex in mice (formalin and writhing tests, resp.). When the hot plate test was conducted, borneol (in higher dose) produced an inhibition (P<0.05) of the nociceptive behavior. Such results were unlikely to be provoked by motor abnormality. Additionally, borneol-treated mice reduced the carrageenan-induced leukocytes migration to the peritoneal cavity. Together, our results suggest that borneol possess significant central and peripheral antinociceptive activity; it has also anti-inflammatory activity. In addition, borneol did not impair motor coordination.

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.

Antinociceptive and Antiedematogenic Activities of Andrographolide Isolated From Andrographis paniculata in Animal Models

2009 ◽  
Vol 11 (3) ◽  
pp. 293-301 ◽  
Author(s):  
M.R. Sulaiman ◽  
Z.A. Zakaria ◽  
A. Abdul Rahman ◽  
A.S. Mohamad ◽  
M.N. Desa ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Animal Models ◽  
Motor Coordination ◽  
Human Studies ◽  
Andrographis Paniculata ◽  
Antinociceptive Activity ◽  
Paw Edema ◽  
Hot Plate ◽  
Experimental Animals

The current study was performed to evaluate the antinociceptive and antiedematogenic properties of andrographolide isolated from the leaves of Andrographis paniculata using two animal models. Antinociceptive activity was evaluated using the acetic acid— induced writhing and the hot-plate tests, while antiedematogenic activity was measured using the carrageenan-induced paw edema test. Subcutaneous (s.c.) administration of andrographolide (10, 25, and 50 mg/kg) did not affect the motor coordination of the experimental animals but produced significant (p < .05) antinociceptive activity when assessed using both tests. However, 2 mg/kg naloxone failed to affect the 25 mg/kg andrographolide activity in both tests, indicating that the activity was modulated via nonopioid mechanisms. Furthermore, andrographolide showed significant (p < .05) antiedematogenic activity. In conclusion, the results obtained suggest that andrographolide has antinociceptive and antiedematogenic activities; it may be useful for treating pain and inflammation once human studies are conducted.

scholarly journals ANALGESIC ACTIVITY OF HYDROALCOHOLIC EXTRACT OF AERIAL PARTS OF MALVASTRUM COROMANDELIANUM

2016 ◽  
Vol 9 (5) ◽  
pp. 146 ◽  
Author(s):  
Bhupesh Chander Semwal ◽  
Kalyani D ◽  
Rohit B
Keyword(s):  
Emotional Experience ◽  
Peak Effect ◽  
Tail Flick ◽  
Hot Plate ◽  
Standard Drug ◽  
Hydroalcoholic Extract ◽  
Thermally Induced ◽  
Aerial Parts ◽  
Antinociceptive Effects ◽  
Malvastrum Coromandelianum

ABSTRACTObjective: The aim of this study is to explore the antinociceptive property of hydroalcoholic extract of Malvastrum coromandelianum. Pain is anunpleasant sensory and emotional experience associated with actual and potential tissue damage. Various types of pain are seen in humans, somatic,visceral, and neuropathic pain. M. coromandelianum belongs to Malvaceae family. Traditionally, it is used as an emollient, anti-inflammatory, analgesic,and antidysenteric.Methods: The antinociceptive effects of hydroalcoholic extract of M. coromandelianum (HEMC) were evaluated by tail-flick, hot-plate, and acetic acidinduced writhing method. Rats were divided into four groups. The first group which served as control was administered with aqueous 1% tragacanthsuspension. The second group received standard drug, morphine (5 mg/kg) orally as a suspension. Third and fourth group received HEMC (200 and400 mg/kg) and served as test drug treatment group, 30 minutes after treatment the reaction time and number of writhes was noted.Results: HEMC produced significant antinociceptive effects against thermally induced pain. In tail-flick method, the peak effect of HEMC 400 mg/kgwas shown at 60 minutes which is nearly equal to the peak effect of morphine 5 mg/kg. In hot-plate method, the HEMC showed significant analgesiceffect up to 3 hrs after the treatment, whereas morphine showed significant effect up to 6 hrs.Conclusion: On the basis of finding, it may conclude that the HEMC shows its central analgesic action probably through inhibition of central painreceptors, whereas peripheral analgesic effect may be mediated by prostaglandin inhibition.Keywords: Pain, Analgesia, Hydroalcoholic extract of Malvastrum coromandelianum, Morphine.

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