Antinociceptive Effect of Clomipramine Through Interaction with Serotonin 5-Нт2 And 5-Нт3 Receptor Subtypes

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.

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Preparation and Analysis of New 1,3,5-Trisubstituted-2-Pyrazolines Derivative for Their Analgesic Potential

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i57a33979 ◽

2021 ◽

pp. 153-164

Author(s):

Jitendra Kumar Chaudhary ◽

Alok Pal Jain ◽

O. P. Tiwari

Keyword(s):

Acetic Acid ◽

Analgesic Effect ◽

Latency Time ◽

Hot Plate ◽

Phenyl Hydrazine ◽

Hot Plate Test ◽

Test Technique ◽

Plate Test ◽

Withdrawal Latency ◽

In Series

The goal of the study was to develop, synthesise, and characterise a novel 1,3,5-trisubstituted-2-pyrazolines derivative, as well as to assess its analgesic potential. The reaction of chalcone derivatives with 4-hydrazinylbenzene sulfonamide hydrochloride and phenyl hydrazine hydrochloride yielded 1,3,5-tri-substituted-2-pyrazolines derivatives. The IR, 1HNMR, and mass spectrum analyses were used to characterise a total of sixteen substances. Analgesic activity of the proposed substances has been tested. The analgesic effect of the produced compounds was tested using two methods: the hot plate test technique and acetic acid induced writhing in mice. To compare the effectiveness, pentazocine and acetyl acetic acid were utilised as reference drugs. The hot plate test technique and acetic acid induced writhing in mice were used to assess the analgesic effect of the 16 produced chemical series A1-A8, and B1-B8. The evaluation's outcomes were viewed using Pentazocine and acetyl acetic acid as the standard drugs. In a 90-minute hot plate test, compounds A2 (10.30 s), A4 (9.45 s), A7 (11.65 s), and A8 (11.26 s) showed a delay in paw withdrawal latency time. Compounds B2 (9.10 s) and B7 (10.42 s) prolong the paw withdrawal latency time after 90 minutes in series B1-B8, reduce the pain feeling, and inhibit pain induced by heat methods. Compounds A2, A5, A6, A7, and A8 from Series A1-A8 showed 83.00, 76.01, 80.34, 86.99, 88.15 percent inhibition, substantially (p0.05 and p0.001, respectively), and decreased the number of wriths caused by 0.6 percent acetic acid at a dosage of 10 mg/kg. Acetylsalicylic acid (10 mg/kg) appears to be more successful in lowering the number of wriths, with a 99.0% reduction in the number of wriths (p0.001). B1, B3, and B4 have the least amount of active activity. These all finding suggest that these synthesized compounds have the potential as analgesic agent.

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Analgesic Effect of Dayak Onion (Eleutherine americana (Aubl.) Merr.) on Mice (Mus musculus) by Hot Plate Test Method

Biomolecular and Health Science Journal ◽

10.20473/bhsj.v4i1.26915 ◽

2021 ◽

Vol 4 (1) ◽

pp. 22

Author(s):

Muhammad Hafizh ◽

Danti Nur Indiastuti ◽

Indri Safitri Mukono

Keyword(s):

Response Time ◽

Analgesic Effect ◽

Latency Period ◽

Test Method ◽

Control Group ◽

Test Results ◽

Hot Plate ◽

Hot Plate Test ◽

Plate Test ◽

Eleutherine Americana

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.

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A Novel Uni-Acupoint Electroacupuncture Stimulation Method for Pain Relief

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/nep104 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 9

Author(s):

Chuansen Niu ◽

Hongwei Hao ◽

Jun Lu ◽

Luming Li ◽

Zhirong Han ◽

...

Keyword(s):

Pain Relief ◽

Analgesic Effect ◽

Control Group ◽

Hot Plate ◽

Hot Plate Test ◽

Plate Test ◽

Analgesic Effects ◽

Significant Difference ◽

Stimulation Method ◽

Relief Effect

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.

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The Analgesic Effect of Aconitum Sinomontanum Nakai Pharmacopuncture in Sprague-Dawley Rats

Journal of Acupuncture Research ◽

10.13045/jar.2020.00409 ◽

2021 ◽

Vol 38 (2) ◽

pp. 140-145

Author(s):

Jung Hee Lee ◽

Yun Kyu Lee ◽

Hyun-Jong Lee ◽

Jae Soo Kim

Keyword(s):

Analgesic Effect ◽

Positive Control ◽

Negative Control ◽

Control Group ◽

Sprague Dawley ◽

Hot Plate ◽

Hot Plate Test ◽

Lidocaine Group ◽

Analgesic Effects ◽

Sd Rats

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.

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Anti-nociceptive and anti-inflammatory effects of an aqueous extract of blended leaves of Ocimum gratissimum and Psidium guajava

Clinical Phytoscience ◽

10.1186/s40816-019-0130-2 ◽

2019 ◽

Vol 5 (1) ◽

Author(s):

Akinyinka O. Alabi ◽

Abayomi M. Ajayi ◽

Osarume Omorogbe ◽

Solomon Umukoro

Keyword(s):

Acetic Acid ◽

Aqueous Extract ◽

Psidium Guajava ◽

Antinociceptive Activity ◽

Hot Plate ◽

Hot Plate Test ◽

Promising Alternative ◽

Plate Test ◽

Ocimum Gratissimum ◽

Anti Inflammatory

Abstract Background To investigate the antinociceptive and anti-inflammatory activities of aqueous extract of a blended mixture of dried leaves of Ocimum gratissimum and Psidium guajava, a traditional analgesic drug polyherbal (TADP) used as a remedy for pain-related conditions. Methods Antinociceptive activity of TADP (100, 200 and 400 mg/kg) was evaluated in the hot plate test and acetic acid-induced nociception in mice while the anti-inflammatory was evaluated in carrageenan-induced paw oedema in rats. Levels of nitrite, myeloperoxidase, glutathione and malondialdehyde were assayed in carrageenan-induced paw tissue. Results TADP (200 and 400 mg/kg) significantly prolong the latency time in the hot-plate test. TADP (100–400 mg/kg) produced a dose-dependent significant inhibition of the acetic-acid induced abdominal constriction. The antinociceptive activity of TADP in the presence of naloxone and atropine was not reversed whereas yohimbine and glibenclamide significantly reversed it. TADP (100, 200 and 400 mg/kg) significantly reduced the swelling in the carrageenan-induced oedema model and also produced a reduction in the nitrite and myeloperoxidase level. TADP (400 mg/kg) significantly reduced malondialdehyde concentration and increase glutathione level in the carrageenan-induced rat paw. TADP significantly decrease the number of cellular infiltrates in the histopathological assessment. Conclusion These results indicate that polyherbal product containing blended leaves of Ocimum gratissimum and Psidium guajava possess antinociceptive and anti-inflammatory properties, hence represents a promising alternative remedy in inflammation-induced pain.

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Enhancement of morphine-induced antinociception after electroconvulsive shock in mice

Molecular Pain ◽

10.1177/1744806921992628 ◽

2021 ◽

Vol 17 ◽

pp. 174480692199262

Author(s):

Ken Iwata ◽

Yukio Takamatsu ◽

Nagafumi Doi ◽

Kazutaka Ikeda

Keyword(s):

Dose Response ◽

Response Curve ◽

Antinociceptive Effect ◽

Dose Response Curve ◽

Expression Level ◽

Morphine Injection ◽

Hot Plate ◽

Hot Plate Test ◽

Plate Test ◽

Pain Patients

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.

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Analgesic Activity of the Kappa Opioid Receptor Agonist RU-1205 in Rats

Journal of Clinical and Health Sciences ◽

10.24191/jchs.v3i2.7275 ◽

2018 ◽

Vol 3 (2) ◽

pp. 13 ◽

Cited By ~ 2

Author(s):

AA Spasov ◽

OY Grechko ◽

DM Shtareva ◽

AI Raschenko ◽

Natalia Eliseeva ◽

...

Keyword(s):

Opioid Receptor ◽

Analgesic Activity ◽

Analgesic Effect ◽

Physical Dependence ◽

Receptor Activation ◽

Kappa Opioid Receptor ◽

Kappa Opioid ◽

Hot Plate ◽

Hot Plate Test ◽

Plate Test

Introduction: Opioid analgesics are the most efficient and widely used drugs for the management of moderate to severe pain. However, side effects associated with mu receptor activation, such as respiratory depression, tolerance and physical dependence severely limit their clinical application. Currently, the kappa-opioid system is the most attractive in terms of the clinical problem of pain, because kappa-agonists do not cause euphoria and physical dependence. The purpose of this study was to evaluate the antinociceptive effect of the novel compound - RU-1205. Methods: The analgesic activity of RU-1205 was studied on nociceptive models that characterize the central and peripheral pathways of pain sensitivity (hot plate test, electrically induced vocalisation, formalin test, writhing test). Results: RU-1205 exhibited highly potent antinociceptive effects in rodent models of acute pain with ED50 values of 0.002 - 0.49 mg /kg. Pretreatment with the κ-opioid receptor antagonist norBinaltorphimine significantly attenuated the analgesic activity of investigated substance in a hot plate test. Conclusions: It was established that the compound shows a significant dose-dependent central and peripheral analgesic effect. It was assumed kappa-opioidergic mechanism of analgesic effect of RU-1205.

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Analgesic effect of the aqueous extract of Artimisia herba alba Arial part

Al-Qadisiyah Journal of Veterinary Medicine Sciences ◽

10.29079/vol9iss3art117 ◽

2010 ◽

Vol 9 (3) ◽

pp. 28

Author(s):

Sh. M. Al-khazrji , and I. K. Khalil

Keyword(s):

Acetic Acid ◽

Aqueous Extract ◽

Cold Water ◽

Hot Plate ◽

Hot Plate Test ◽

Writhing Test ◽

Plate Test ◽

Analgesic Effects ◽

Rats And Mice ◽

Dose Dependent

The present study was aimed to investigate the analgesic effects of the aqueous extract of Artemisia herba alba Arial part in rats and mice ( AEAHA ). The AEAHA (400- 700 mg/kg; p.o.) was evaluated for its analgesic activity by employing acetic acid-induced writhing test, hot plate test and tail immersion tests i.e. in hot and cold water. AEAHA (400- 700 mg/kg; p.o.) showed significant (P<0.01) reduction in the number of writhing induced by acetic acid,increased reaction time in hot plate test and elevated pain threshold in hot and cold water tests. AEAHA exhibited the dose-dependent analgesic effects

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Analgesic Effects of Vigna unguiculata subsepecies dekindtiana in Mice

Journal of Advances in Medical and Pharmaceutical Sciences ◽

10.9734/jamps/2020/v22i730181 ◽

2020 ◽

pp. 10-22

Author(s):

Adekunle T. Adegbuyi ◽

Moses A. Akanmu ◽

G. Olayiwola ◽

Abayomi O. Sijuade

Keyword(s):

Acetic Acid ◽

Receptor Antagonist ◽

Vigna Unguiculata ◽

Analgesic Effect ◽

Methanol Extract ◽

Positive Control ◽

Hot Plate ◽

Thermal Tests ◽

Writhing Test

In the present study, we investigated the antinociceptive effects of the plant Vigna unguiculata spp dekindtiana using chemical and thermal tests in mice. The peripheral and the central analgesic activities of the methanol extract and its fractions were investigated in-vivo in albino mice using acetic acid induced-writhing test and hot plate models respectively. The result of the central analgesic effect showed that the methanol extract (VUME) at 400 mg/kg produced a significant (p<0.05) delay in reaction time in mice on hot plate compared to the control. Various fractions of the extract showed more potency compared to the crude extract. In acetic writhing model, the extract and the fractions demonstrated dose dependent reduction in writhing reaction induced by acetic acid in mice. The reduction was significant when compared to control which was suggestive of the analgesic effect of the plant. It was also seen that the extract and fractions showed an improved analgesic effect compared to diclofenac used as positive control in this model. Yohimbine (alpha adrenergic receptor antagonist) and cyproheptadine (serotonergic receptor antagonist) reversed the antinociceptic effect of the fractions in the hot plate model demonstrating the possibility of adrenergic and serotonergic involvement in eliciting the analgesic effect. Naloxone on the other hand, caused a reversal only in the butanol fraction meaning that this fraction may contain active principles that may mediate their analgesic effect through the opioid mechanism. In the writhing test, yohimbine abolished the analgesic effect of both hexane and butanol fractions. This may therefore, suggest that the analgesic effect of these fractions may be mediated through adrenergic pathway. In conclusion, the plant V. unguiculata subspecies dekindtiana possesses active principles with potential analgesic activity, establishing the folkloric use of the plant in managing pain.

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