The Antinociceptive Effect of a Benzopyran (HP1) Isolated fromHypericum polyanthemumin Mice Hot-Plate Test is Blocked by Naloxone

Planta Medica ◽  
2010 ◽  
Vol 76 (13) ◽  
pp. 1419-1423 ◽  
Author(s):  
Juliana Haas ◽  
Alice Viana ◽  
Ana Machado Heckler ◽  
Gilsane Poser ◽  
Stela Kuze Rates
2021 ◽  
Vol 17 ◽  
pp. 174480692199262
Author(s):  
Ken Iwata ◽  
Yukio Takamatsu ◽  
Nagafumi Doi ◽  
Kazutaka Ikeda

Electroconvulsive therapy (ECT) has been applied for chronic pain for decades. The amounts of opioids to treat pain are sometimes reduced after a series of ECT. The effect of ECT on morphine-induced analgesia and its mechanism underlying the reduction of morphine requirement has yet to be clarified. Therefore, we administered electroconvulsive shocks (ECS) to mice and investigated the antinociceptive effect of morphine in a hot plate test. We examined the expression level of µ-opioid receptor in the thalami of mice 25 h after administration of ECS compared to the thalami of mice without ECS administration using western blotting. ECS disturbed the development of a decrease in the percentage of maximal possible effect (%MPE), which was observed 24 h after a morphine injection, when ECS was applied 25, 23, 21, and 12 h before the second administration of morphine. We also examined the effect of ECS on the dose-response curve of %MPE to morphine-antinociception. Twenty-five hours after ECS, the dose-response curve was shifted to the left, and the EC50 of morphine given to ECS-pretreated mice decreased by 30.1% compared to the mice that were not pretreated with ECS. We also found that the expression level of µ-opioid receptors was significantly increased after ECS administration. These results confirm previous clinical reports showing that ECT decreased the required dose of opioids in neuropathic pain patients and suggest the hypothesis that this effect of ECT works through the thalamus.


Folia Medica ◽  
2012 ◽  
Vol 54 (4) ◽  
pp. 69-77 ◽  
Author(s):  
Ilia D. Kostadinov ◽  
Delian P. Delev ◽  
Ivanka I. Kostadinova

Abstract INTRODUCTION: Tricyclic antidepressants are used in the treatment of various pain syndromes. The antidepressant clomipramine inhibits predominantly the reuptake of serotonin in the central nervous system. The mechanism of its analgesic effect is not fully understood. The AIM of the present study was to find experimentally any dose-effect dependence in the analgesic effect of clomipramine and the involvement of the 5-НТ2 and 5-НТ3 receptors in the mechanism of this effect. Material and methods: Fifty male Wistar rats were used in the study allocated to five groups (10 animals each): a saline treated control group, one positive control group treated with metamizole and three experimental groups treated with intraperitoneally administered clomipramine in doses of 5, 10 and 20 mg/kg bw, respectively. To study the role of 5-НТ2 and 5-НТ3 receptors in this effect we used another five groups (10 animals each): control, positive control and three experimental groups treated with clomipramine only, clomipramine and granisetrone and clomipramine and cyproheptadine, respectively. Three nociceptive tests were used: the hot plate test, analgesimeter and the acetic acid-induced writhing test. To gauge the antinociceptive action we used the increased latency in the hot plate test expressed as maximum possible effect % (%MPE), the increase in paw pressure to withdraw the hind paw in analgesimeter and decrease in the number of spinal cord writhes in the acetic acid test. RESULTS: Clomipramine in a dose of 20 mg/kg bw significantly increased the %MPE in hot plate test and the pressure to withdraw the hind paw in the analgesimeter when compared with the control. In the acetic acid test clomipramine decreased non-significantly the number of writhes compared with the controls. Granisetrone reduced non-significantly the antinociceptive effect of clomipramine in all tests. Cyproheptadine potentiated the analgesic effect of clomipramine in acetic acid test and decreased it significantly in the hot plate test. In analgesimeter cyproheptadine decreased significantly the paw pressure to withdraw the tested hind paw at 1 hour and non-significantly at 2 hours. CONCLUSION: Clomipramine in the dose of 20 mg/kg bw has a pronounced antinociceptive affect towards thermal and mechanical pain stimulation. The 5-HT2 and 5-HT3 receptor subtypes are very likely involved in the mechanism of this effect.


Author(s):  
Erdem N. Duman ◽  
Murat Kesim ◽  
Mine Kadioglu ◽  
Cunay Ulku ◽  
Nuri I. Kalyoncu ◽  
...  

2010 ◽  
Vol 9 (3) ◽  
pp. 56
Author(s):  
W. H. Al-Shebani, And F. J. Al-Tahan

The present study was designed to investigated the antinociceptive effect of the waterysuspension of Nigella sativa seeds compared with that of Naproxen by using hot plate test, whichmainly measures the threshold of stimulus required to elicit a response , in mice at 30, 60, 90, 120minutes after administration of the test agents. Twenty four albino Swiss mice of either sex weredivided in four groups with (6) animals each, the first group was treated orally with 1000 mg/kgBW of watery suspension of Nigella seeds, the second group was treated orally with naproxen atdose of 500 mg/kg BW ,the third group drenched with 500mg/kg BW of watery suspension ofNigella seeds and 250 mg/kg BW of naproxen ,whereas the last group serve as control. Nigellasativa seeds suspension significantly (p<0.05) prolonged the latency of response at all posttreatmentobservation times (30, 60, 90 and 120 minutes) , the analgesic action of naproxen wasdiminished with time compared with Nigella seeds.Combination of equal amounts of Nigellaseeds and Naproxen (half the originally used doses) caused significant increment (p<0.05) ofanalgesic reaction time longer than shown by each agent when given alone indicating an obvioussynergistic effect between watery suspension of Nigella seeds and Naproxen.


2018 ◽  
Vol 28 (2) ◽  
pp. 455-460
Author(s):  
Vesela Kokova ◽  
Elisaveta Apostolova ◽  
Lyudmil Peychev ◽  
Zhivko Zhivko ◽  
Kostadin Kanalev

Introduction: Etifoxine is a nonbenzodiazepine anxiolytic and anticonvulsant drug. It enhances GABAergic transmission directly by binding to β2 and/or β3 subunits of the GABAA receptor complex and indirectly via stimulation of neurosteroid production after the activation of 18 kDa translocator protein (TSPO). Retigabine is an anticonvulsant drug which activates low-threshold voltage-gated potassium channels. Anticonvulsant drugs reduce hyperexcitability and are currently extensively studied for possible antinociceptive activity. The aim of this study is to compare the antinociceptive effect of etifoxine and retigabine in rats. Materials and methods: The research included forty male Wistar rats, divided into five groups (n = 8). They were treated intraperitoneally with: 1st group (control) – saline 0,1ml/100g bw, 2nd group–metamizole natrii 150 mg/kg bw, 3rd group – etifoxine 50 mg/kg bw, 4th group –retigabine 5 mg/kg bw and 5th group – retigabine 15 mg/kg bw. The antinociceptive effect was evaluated with hot plate test and analgesy-meter test. The statistical analysis was performed using SPSS.17. Results: Etifoxine did not prolong the latency time in hot plate test and did not increase the withdrawal latency in analgesy-meter test, compared to the animals treated with saline. In hot plate test, retigabine in dose 15 mg/kg bw significantly increased the latency time at the second and third hour, compared to the control group (p<0.05). In analgesy-meter test, a significant increase of the withdrawal latency between retigabine and control animals occurred only at dose 15 mg/kg bw at first hour after single administration (p<0.05). Conclusions: The obtained experimental data show that etifoxine in dose 50 mg/kg bw does not have antinociceptive effect. Single administration of retigabine 15 mg/kg bw reduced painful thermal and mechanical stimuli in rats. The presence of KCNQ channels in the neuronal pathways of pain suggests that the antinociceptive effect of retigabine is maybe based on the activation of low-threshold potassium channels.


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Jo-Young Son ◽  
Jae-Seong Lim ◽  
Jae-Hyung Park ◽  
Jae-Hyeong Park ◽  
Myeong-Shin Kim ◽  
...  

Mannitol has recently been reported to be effective in enhancing the antinociceptive efficacy of lidocaine. No single study to date, however, has compared diphenhydramine with and without mannitol for nociceptive processing as an alternative local anesthetic. In this study, we examined the antinociceptive efficacy enhancements of diphenhydramine when combined with mannitol. Male Sprague-Dawley rats weighing 230–260 g were used in a hot plate test to evaluate the antinociceptive effects of diphenhydramine. All chemicals were dissolved in isotonic normal saline and administered subcutaneously into the plantar surface of the right hind paw at 10 min before the hot plate test. A subcutaneous injection of 0.5% or 1% diphenhydramine produced significant inhibition of the withdrawal latency time compared with the vehicle treatment. Antinociceptive effects appeared 10 min after the diphenhydramine injections and persisted for over 30 min. The antinociceptive effects of 1% diphenhydramine were not statistically different from those of 1% lidocaine. Although a subcutaneous injection of a 0.5 M mannitol solution alone did not affect the withdrawal latency time, 1% diphenhydramine with 0.5 M mannitol significantly enhanced antinociception. A subcutaneous injection of 1% diphenhydramine with epinephrine (1 : 100,000) solution did not increase the antinociceptive effect of the diphenhydramine. These results suggest that diphenhydramine with mannitol can be used as an alternative local anesthetic.


2003 ◽  
Vol 98 (3) ◽  
pp. 741-747 ◽  
Author(s):  
Aránzazu Roca-Vinardell ◽  
Antonio Ortega-Alvaro ◽  
Juan Gibert-Rahola ◽  
Juan A. Micó

Background It has been proposed that serotonin participates in the central antinociceptive effect of acetaminophen. The serotonin activity in the brainstem is primarily under the control of 5-HT1A somatodendritic receptors, although some data also suggest the involvement of 5-HT1B receptors. In the presence of serotonin, the blockade of 5-HT(1A/B) receptors at the level of the raphe nuclei leads to an increase in serotonin release in terminal areas, thus improving serotonin functions. This study examines the involvement of 5-HT(1A/B) receptors in the antinociceptive effect of acetaminophen in mice. Methods The effects of acetaminophen (600 mg/kg intraperitoneal) followed by different doses of antagonists (WAY 100635 [0.2-0.8 mg/kg subcutaneous] and SB 216641 [0.2-0.8 mg/kg subcutaneous]) or agonists (8-OH-DPAT [0.25-1 mg/kg subcutaneous] and CP 93129 [0.125-0.5 mg/kg subcutaneous]) of 5-HT1A and 5-HT1B receptors, respectively, were determined in the hot-plate test in mice. Results Acetaminophen (300-800 mg/kg) showed a dose-dependent antinociceptive effect in the hot-plate test in mice. WAY 100635 (0.2-0.8 mg/kg; 5-HT1A antagonist) induced an increase in the antinociceptive effect of 600 mg/kg acetaminophen, but this increase was not dose related. Conversely, 8-OH-DPAT (0.25-1 mg/kg; 5-HT1A agonist) decreased the antinociceptive effect of acetaminophen. SB 216641 (0.2-0.8 mg/kg; 5-HT1B antagonist) induced a dose-related increase in the antinociceptive effect of acetaminophen, and CP 93129 (0.25 mg/kg; 5-HT1B agonist) significantly decreased the antinociceptive effect of acetaminophen. Conclusions These results suggest that the combination of acetaminophen with compounds having 5-HT1A and 5-HT1B antagonist properties could be a new strategy to improve the analgesia of acetaminophen, thanks to its mild serotonergic properties.


2017 ◽  
Vol 4 (03) ◽  
pp. e82-e88 ◽  
Author(s):  
Gabriela Meirelles ◽  
Henrique Bridi ◽  
Eveline Stolz ◽  
Helder Teixeira ◽  
Gilsane von Poser ◽  
...  

AbstractThe impact of nanoemulsification on the antinociceptive effect of benzopyran HP1 in a mice hot plate test was investigated. For comparison, the same experiments were performed with HP1-free form. The durability of the antinociceptive effect was analyzed at 60, 120 and 180 min. The results revealed that HP1 was successfully incorporated into a nanoemulsion system, given its high solubility in the oil phase. Regarding the pharmacological effect, HP1 (15, 30, 45, and 60 mg/kg, p.o.), both forms, displayed the pattern of a bell-shaped dose-response curve. HP1-loaded nanoemulsion displayed the maximal antinociceptive effect at a lower dose than the HP1-free form. The highest effect of the free compound was observed at 45 mg/kg, while the HP1-loaded nanoemulsion displayed the same effect at 30 mg/kg. These results suggest that the observed effect might be attributable to an increase in solubility and, thus, the enhancement of compound absorption. Regarding the durability of the antinociceptive effect, the outcomes demonstrated that the HP1-free form lost its antinociceptive effect at 120 min, while the HP1-loaded nanoemulsion kept its effect until 180 min. These findings corroborate literature data, where studies have demonstrated absorption enhancement when a compound was loaded in a nanoemulsion system.


Planta Medica ◽  
2017 ◽  
Vol 83 (17) ◽  
pp. 1329-1334 ◽  
Author(s):  
Henrique Bridi ◽  
Gabriela Meirelles ◽  
Sérgio Bordignon ◽  
Stela Rates ◽  
Gilsane von Poser

AbstractA new dimeric acylphloroglucinol, denudatin A (1), was isolated from the flowering aerials parts of Hypericum denudatum, along with the known phloroglucinols selancin A (2), hyperbrasilol A (3), uliginosin B (4), and isouliginosin B (5). The structure of 1 was elucidated using 1D, 2D NMR, and MS experiments, and by comparison with previously reported data for Hypericum dimeric acylphloroglucinols. Denudatin A (1) and selancin A (2) were administered orally to mice displaying antinociceptive activity in the hot plate test. The compounds did not induce motor impairment in the rotarod apparatus.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 243
Author(s):  
Joris C Verster ◽  
Andrew Scholey ◽  
Thomas A Dahl ◽  
Jacqueline M Iversen

SJP-005 (a combination of ketotifen and ibuprofen) is being developed as a potential treatment for pain and for opioid use disorder. It is therefore important to investigate the potential antinociceptive properties of SJP-005. Two studies were conducted to evaluate the potential effects of SJP-005 in rats. Study 1 applied the von Frey test to examine the antinociceptive effect of morphine with and without SJP-005 in adjuvant-induced hypersensitivity to tactile stimulation. In a double-blind, between-groups design, groups of rats (n = 10 each) received morphine at 3, 10, or 30 mg/kg bodyweight (bw) (subcutaneous injection) with or without SJP-005 (oral). Mechanic allodynia and paw volume were assessed before and after treatment. Study 2 utilized the hot plate test. Using a crossover design, groups of rats (n = 10 each) received either morphine at 3, 10, or 30 mg/kg bw (subcutaneous injection) preceded by oral administration of placebo (Week 1) or SJP-005 (Week 2). In Study 1, in the von Frey up-and-down test, Δ paw withdrawal responses in Group 1 (3 mg/kg bw morphine) were significantly lower compared to those in Group 4 (3 mg/kg bw morphine plus SJP-005), whereas the differences in Δ paw withdrawal between Group 2 and Group 5 (10 mg/kg bw morphine with and without SJP-005) and between Group 3 and Group 6 (10 mg/kg bw morphine with and without SJP-005) did not reach statistical difference. Trendline analysis of the dose–response relationship for the morphine + placebo groups and morphine + SJP-005 groups revealed no significant differences in the intercepts and slopes. In Study 2, no significant differences were observed on hot plate performance between morphine and morphine in combination with SJP-005. In conclusion, the findings in the von Frey up-and-down test (Study 1) suggest that animals can withstand higher levels of painful stimuli when SJP-005 is co-administered. This may also suggest a possible opioid sparing effect. However, in the hot plate test (Study 2), animals did not respond more adaptively to stronger painful stimuli after co-administering SJP-005. These observations warrant further investigation of the antinociceptive properties of SJP-005.


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