scholarly journals N-acetylcysteine dose-dependently improves the analgesic effect of acetaminophen on the rat hot plate test

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Samaneh Nakhaee ◽  
Mohammad Dastjerdi ◽  
Hesam Roumi ◽  
Omid Mehrpour ◽  
Khadijeh Farrokhfall

Abstract Background Acetaminophen (APAP) induced hepatotoxicity is a clinically important problem. Up to now, interventive therapy with n-acetylcysteine (NAC) has been considered as a gold-standard treatment for APAP overdose. However, no study has focused on the efficacy of these drugs’ concurrent administration on probable enhancing therapeutic outcomes. Thus, this study was aimed to investigate the analgesic effect of co-administration of NAC and acetaminophen in male rats. The NAC-APAP drug formulation may demonstrate the stranger antinociceptive effect. Methods Forty-eight male Sprague-Dawley rats (12–14 weeks) randomly divided into six equal groups; control, APAP (received 300 mg/kg APAP), NAC (received 600 mg/kg NAC) and APAP+ NAC groups that received simultaneously 300 mg/kg APAP with 200–600 mg/kg NAC (AN200, AN400, AN600). All administrations were done orally for once. The antinociceptive effect was recorded by measurement of latency period on a hot plate in 30, 60, and 90 min after administrations. Results The results showed that NAC’s concurrent administration with APAP, dose-dependently increased APAP analgesic effects (p< 0.0001). Moreover, NAC treatment exhibited an antinociceptive effect in 60 and 90 min, per se. The treatments had no adverse effect on liver enzymes and oxidative stress. Conclusion Co-administration of NAC with APAP can improve the antinociceptive effect of APAP. It is suggested that this compound can enhance analgesic effects of APAP and eventually lead to a reduction in acetaminophen dose. Further studies are needed to evaluate the molecular mechanism of this hyper analgesic effect.

2021 ◽  
Vol 38 (2) ◽  
pp. 140-145
Author(s):  
Jung Hee Lee ◽  
Yun Kyu Lee ◽  
Hyun-Jong Lee ◽  
Jae Soo Kim

Background: Aconitum sinomontanum Nakai (ASN) has been reported to have analgesic effects. In this study an animal model of pharmacopuncture using ASN (100-500 mg/kg) was examined.Methods: Sprague-Dawley (SD) rats (n = 40) were randomly assigned to ASN-Low (1 mg/mL, 1.8 mL, ASN-L), ASN-Intermediate (5 mg/mL, 1.8 mL, ASN-M), ASN-High (10 mg/mL, 1.8 mL, ASN-H), negative control (0.2 mL normal saline), and positive control (0.2 mL 0.5% lidocaine) groups. All experiments were administered to the rats’ left hind leg. The analgesic response was assessed by monitoring the physical (hot plate, and von Frey test) and chemical (formalin) responses to pain.Results: All ASN pharmacopuncture groups demonstrated significant differences in pain response to the hot plate test, von Frey test, and formalin test, compared to the control group (p < 0.05). The response of the ASN-M group and ASN-H groups to the hot plate, the formalin, and the von Frey tests were significantly different, compared to the lidocaine group (p < 0.05).Conclusion: ASN pharmacopuncture had a significant analgesic effect on SD rats in response to physical and chemical models of pain.


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.


2021 ◽  
Vol 4 (1) ◽  
pp. 22
Author(s):  
Muhammad Hafizh ◽  
Danti Nur Indiastuti ◽  
Indri Safitri Mukono

Introduction: Pain is an unpleasant experience that reduces a person's quality of life. Pain related complain can be treated by administering analgesic drugs. Several studies show that the availability of analgesics is still low, especially opioid analgesics. Dayak onion (Eleutherine americana (Aubl.) Merr.) are used by the Dayaks to relieve pain. Several empirical studies have shown that Dayak onion contain compounds including quercetin as a potential analgesic. This research aimed to investigate the potential analgesic effect of Dayak onion using hot plate method.Methods: The research was conducted experimentally on 36 BALB/c male mice which randomly divided into 6 different treatment groups of Dayak onion exctract, aspirin, codein and aquadest. Each group were thermally pain-induced for latency period measurement by the hot plate test method. Obtained data were processed using Analysis of Variance (ANOVA) followed by Dunnett test.Results: There was a difference in the latency period between the baseline response time and the response time after being treated in each group. ANOVA test results showed significant results (p<0.05) so that the resulting latency period was significant. Dunnett test results showed significant results (p<0.05) in negative control group. Based on these results, Dayak onion are proven to have an analgesic effect on heat stimulation.Conclusion: Dayak onion possess significant analgesic effect on thermally pain-induced mice. Dayak onion extract 90 mg/kg mouse produced better analgesic effects than aspirin 65 mg/kg mouse.


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.


2006 ◽  
Vol 105 (3) ◽  
pp. 574-580 ◽  
Author(s):  
Tatsuya Hashimoto ◽  
Yoji Saito ◽  
Kazuo Yamada ◽  
Nobumasa Hara ◽  
Yumiko Kirihara ◽  
...  

Background Morphine can desensitize mu-opioid receptor (MOR), but it does not cause internalization of the receptor after binding. Acute desensitization of MOR impairs the efficiency of signaling, whereas the receptor internalization restores the cell responsiveness to the agonists. Thereby, the property of morphine may limit the analgesic effects of this opiate drug. It has been shown that [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO), a potent MOR agonist inducing the internalization, facilitates morphine to internalize MOR, suggesting that MOR agonists with low relative activity versus endocytosis (RAVE) values such as DAMGO can potentiate analgesic effects of morphine through stimulating MOR internalization. The authors examined whether the acute analgesic effect of morphine can be potentiated by low relative activity versus endocytosis agonists DAMGO and fentanyl. Methods Rats injected intrathecally with opioids were subjected to a hot plate test for antinociceptive effect. Immunostained spinal dorsal horn was analyzed by confocal microscopy. Results Fentanyl induced MOR internalization to a lesser extent than DAMGO at equianalgesic doses. Coadministration of fentanyl promoted morphine-induced MOR internalization. The analgesic effect of morphine was greatly potentiated together with decrease in the relative activity versus endocytosis value when MOR internalization was induced by coadministration of a subanalgesic dose of DAMGO or fentanyl. In contrast, the combination of DAMGO and fentanyl increased neither the analgesic effect nor the internalization of MOR. Conclusions The results suggest that the coadministration of morphine with MOR-internalizing agonist is clinically applicable to develop successful pain-management regimens to achieve satisfactory analgesia using less morphine.


Author(s):  
Lyudmyla Derymedvid ◽  
Lyudmyla Korang

Opioid and non-narcotic analgesics, non-steroidal anti-inflammatory agents, anesthetics, antidepressants, myorelaxants, combined agents and phytopreparations are widely used for the treatment of pain syndrome. One of the promising phytogenic objects with potential analgesic properties is the Acorus calamus (Sweet Flag). The aim: the purpose of the study is to determine the analgesic effect of the dealcoholized extract of Acorus calamus leaves (DEAL) on a model of pain in the "Hot plate" test and in the test of tail heat immersion. Materials and methods. During the experimental study, the pharmacological methods have been used. The analgesic properties of DEAL were studied in mice on the "Hot plate" model using the Hot / Cold Plate (Bioseb, France) and in the test of the heat immersion in rats. The results. On the models of pain in the "Hot plate" and tail heat immersion tests, the analgesic effect of the dealcoholized extract of Acorus calamus leaves (DEAL) is determined. On the "Hot plate" model, the use of DEAL probably increased the duration of the latency period. According to the analgesic effect of DEAL and metamizol sodium were comparable to each other continues to 1 and 1.5 hours of experiment, but starting with 2 hours of experiment the analgesic action of metamizol sodium statistically exceeded the analgesic effect of DEAL. In the test of heat immersion tail in rats, DEAL increased the latency period of shocking of the rats’ tail compared to the starting background by 43.13 % as well as metamizol sodium by 66.6 %. The studies have shown the presence of moderate analgesic effects of DEAL in the investigated dose. Conclusions. The analgesic effect of a dealcoholized extract of Acorus calamus leaves (DEAL) on a model of pain in the "Hot plate" and heat tail immersion tests has been carried out. Under the "Hot plate" test in mice, DEAL produces a distinct analgesic effect, however, slightly inferior to the severity of metamizol sodium. Presence of moderate analgesic properties of DEAL has been verified in comparison with the metamizel sodium in thetail heat immersion test in rats. The obtained results indicate the influence of DEAL on the central mechanisms of pain formation


2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Chuansen Niu ◽  
Hongwei Hao ◽  
Jun Lu ◽  
Luming Li ◽  
Zhirong Han ◽  
...  

Electroacupuncture stimulation (EAS) has been demonstrated effective for pain relief and treating other various diseases. However, the conventional way of EAS, the bi-acupoint method, is not suitable for basis study of acupoint specificity. Moreover, its operations are inconvenient and difficult to be persevered, especially for long-term, continuous and even imperative treatments. These disadvantages motivate designs of new EAS methods. We present a novel uni-acupoint electrical stimulation method, which is applied at a single acupoint and quite meets the needs of basis study and simpler clinical application. Its pain relief effect has been evaluated by animal tests of Wistar rats. During the experiments, rats were given 30 min 2/100 Hz uni- and bi-acupoint EAS and their nociceptive thresholds before and after EAS were attained by hot-plate test. The analgesic effect was defined as the change of nociceptive threshold and used to evaluate the effectiveness of uni-acupoint EAS for pain relief. The hot-plate test results indicated that analgesic effect of uni-acupoint group was significantly higher than that of the control group and there was no significant difference of analgesic effects between uni- and bi-acupoint EAS. The results suggested that uni-acupoint method was an effective EAS method and had comparable pain relief effect with bi-acupoint method.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Erhan Ozyurt ◽  
Zekiye Bigat ◽  
Bilge Karsli ◽  
Arda Tasatargil ◽  
Inanc Elif Gurer ◽  
...  

Abstract Background This study aims to investigate the histopathological and analgesic effects of intrathecal administration of dexmedetomidine, preservative-free racemic ketamine, and magnesium sulfate in Sprague Dawley rats. This study included 40 male Sprague Dawley rats weighing between 240 and 260 g. After the intrathecal catheterization, the rats were randomly divided into four groups. Following the baseline measurements, no drugs were administered in the control group (group C). Simultaneously, 0.02 ml (1 μgr/kg) of dexmedetomidine was administered in group D, 0.02 ml (1 mg/kg) preservative-free racemic ketamine in group K and 0.02 ml (0.05 mg/kg) magnesium sulfate in group M via intrathecal route. Concomitantly, the hot-plate test was used to measure the analgesic effect of drugs. For histopathological evaluation, the rats were sacrificed to obtain the medulla spinalis. Results The hot-plate test revealed that the mean response time was 6.3 ± 1.2 s in baseline measurements without medication. However, prolongation in the mean response times of the drug-administered groups to the hot-plate test was also observed. Upon histopathological examination, myelin degeneration was detected in all study groups. No inflammation was observed in rats in group D, whereas inflammation was noted in only two rats in group K. Concerning the presence of red neurons, the only group that differed from the control group belonged to group K. Conclusions Dexmedetomidine, preservative-free racemic ketamine, and magnesium sulfate have an analgesic effect when administered intrathecally in rats. Of these drugs, preservative-free racemic ketamine stands out as the most histopathologically safe drug.


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.


2011 ◽  
Vol 02 (02) ◽  
pp. 130-136 ◽  
Author(s):  
Keshab Raj Paudel ◽  
SK Bhattacharya ◽  
GP Rauniar ◽  
BP Das

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.


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