scholarly journals MiR-140-5p inhibits morphine tolerance in rats by targeting TLR4

2021 ◽  
Vol 20 (9) ◽  
pp. 1881-1886
Author(s):  
Guihua Liu ◽  
Ying Xiong
Keyword(s):  
Morphine Tolerance ◽  
Luciferase Reporter ◽  
Saline Control ◽  
Maximum Effect ◽  
Tail Flick ◽  
Test Results ◽  
Tlr4 Expression ◽  
Sprague Dawley ◽  
Toll Like Receptor 4 ◽  
Tail Flick Test

Purpose: To determine the influence of miR-140-5p on morphine tolerance in rats.Methods: Sprague-Dawley (SD) rats were randomly divided into morphine tolerance (MT) and saline control (NS) groups, respectively. Rats in MT group were injected with 10 μL (10 μg) morphine twice daily for seven consecutive days while those in NS group were administered the equivalent volume of normal saline. The maximum effect of morphine (MPE) was computed from tail-flick test results. MiR-140-5p mimics and toll-like receptor 4 (TLR4) lentivirus were transfected separately or co-transfected into model rats. MiR-140-5p and TLR4 expression were determined by quantitative real-time polymerase chain reaction (RT-qPCR) or western blotting. Dual-luciferase reporter assay was used to verify the target relationship between miR-140-5p and TLR4.Results: The expression of miR-140-5p was decreased, while the expression of TLR4 increased in morphine-tolerant rats (p < 0.05). TLR4 was a target of miR-140-5p. At 24 and 48 h after injection, MPE clearly increased and TLR4 expression was reduced under miR-140-5p overexpression or TLR4 knockdown (p < 0.05). Moreover, there were no significant changes in MPE or levels of TLR4 when miR-140-5p and TLR4 were co-transfected into morphine-tolerant rats.Conclusion: MiR-140-5p inhibits morphine resistance in rats via targeted regulation of TLR4 expression. These provide a theoretical basis for the clinical management of morphine tolerance.

scholarly journals Modulation of Morphine-induced Antinociception in Acute and Chronic Opioid Treatment by Ibudilast

2009 ◽  
Vol 111 (6) ◽  
pp. 1356-1364 ◽  
Author(s):  
Tuomas O. Lilius ◽  
Pekka V. Rauhala ◽  
Oleg Kambur ◽  
Eija A. Kalso
Keyword(s):  
Cell Activation ◽  
Antinociceptive Effect ◽  
Opioid Analgesics ◽  
Morphine Tolerance ◽  
Tail Flick ◽  
Sprague Dawley ◽  
Tail Flick Test ◽  
Glial Cell Activation ◽  
Sprague Dawley Rats ◽  
Antinociceptive Effects

Background Opioid analgesics are effective in relieving chronic pain, but they have serious adverse effects, including development of tolerance and dependence. Ibudilast, an inhibitor of glial activation and cyclic nucleotide phosphodiesterases, has shown potential in the treatment of neuropathic pain and opioid withdrawal. Because glial cell activation could also be involved in the development of opioid tolerance in rats, the authors studied the antinociceptive effects of ibudilast and morphine in different models of coadministration. Methods Antinociception was assessed using male Sprague- Dawley rats in hot plate and tail-flick tests. The effects of ibudilast on acute morphine-induced antinociception, induction of morphine tolerance, and established morphine tolerance were studied. Results Systemic ibudilast produced modest dose-related antinociception and decreased locomotor activity at the studied doses of 2.5-22.5 mg/kg. The highest tested dose of 22.5 mg/kg produced 52% of the maximum possible effect in the tail-flick test. It had an additive antinociceptive effect when combined with systemic morphine. Coadministration of ibudilast with morphine did not attenuate the development of morphine tolerance. However, in morphine-tolerant rats, ibudilast partly restored morphine-induced antinociception. Conclusions Ibudilast produces modest antinociception, and it is effective in restoring but not in preventing morphine tolerance. The mechanisms of the effects of ibudilast should be better understood before it is considered for clinical use.

scholarly journals Effect of Hydroalcoholic Extract of Hyssop on Acute Pain in Male Rats Using Tail Flick Test

2021 ◽  
Vol 2 (1) ◽  
pp. 15-19
Author(s):  
Amir Larki-Harchegani ◽  
Abbas Ehsanikia ◽  
Sara Ataei ◽  
Fakhriosadat Hosseini ◽  
Rasool Haddadi
Keyword(s):  
Analgesic Effect ◽  
Positive Control ◽  
Male Rats ◽  
Saline Control ◽  
Control Group ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Hydroalcoholic Extract ◽  
Analgesic Effects ◽  
Iranian Traditional Medicine

Background: Iranian traditional medicine uses hyssop (Hyssopus officinalis) as an effective medicinal plant to reduce pain and inflammation in different diseases. Although the anti-inflammatory effect of this plant is proved, there is no study into its analgesic effects. Thus, this study aimed to investigate the analgesic effect of the hydroalcoholic extract from hyssop flowers and upper branches. Methods: This experimental study was conducted on 66 male rats that were divided into several groups including a saline control group, the groups of different doses of hyssop extract, morphine positive control group, the groups of hyssop extract plus morphine, and the most effective dose of the hyssop extract plus naloxone. All injections were administered intraperitoneally, and the pain was measured through the tail flick test. Results: Based on the results, 600 mg/kg was the most effective analgesic hyssop extract dose, and the most analgesic effect was observed at 45 minutes after administration. In addition, the administration of the most effective extract dose (600 mg/kg) plus morphine significantly improved the analgesic effects of morphine (P<0.001). Finally, the administration of naloxone plus the most effective extract dose (600 mg/kg) significantly reduced the analgesic effect of the extract (P<0.05). Conclusion: Overall, the hydroalcoholic extract of hyssop has analgesic effects that are probably applied through opioid receptors.

scholarly journals Onosma bracteatum wall: A Potent analgesic agent

2018 ◽  
Vol 17 (1) ◽  
pp. 36-41 ◽  
Author(s):  
Hina Imran ◽  
Atiq Ur Rahman ◽  
Tehmina Sohail ◽  
S Intasar H Taqvi ◽  
Zahra Yaqeen
Keyword(s):  
Body Weight ◽  
Acetic Acid ◽  
Analgesic Activity ◽  
Latency Period ◽  
Maximum Effect ◽  
Tail Flick ◽  
Significant Activity ◽  
Tail Flick Test ◽  
Writhing Test ◽  
Post Feeding

Background: This study was aimed to find out the central and peripheral analgesic activity of hydro methanolic extract of aerial parts of Onosma bracteatum.Material and methods: The central and peripheral analgesic activity is evaluated by tail flick test and acetic acid induced writhing test at the doses of 50, 100, 250 and 500mg/kg body weight respectively in animal models.Results: The results obtained from Tail flick test revealed that O. bracteatum possesses potent analgesic effects by inducing significant increase in latency period in dose dependent manner at all doses at 1, 2 and 3 hours post feeding respectively. The maximum effect was observed at a dose of 500mg/kg i.e. 258.9% (p<0.05) at 3hrs post feeding. Diclofenac sodium (5mg/kg body weight) run as standard also increased the latency period continuously and highest activity was noted at 3hr i.e. 284.5% (p<0.05). Acetic acid induced writhing test also showed significant activity in a similar manner by O. bracteatum i.e 54% (p<0.05) at 500mg/kg while standard drug Diclofenic sodium (5mg/kg body weight) showed 45.9% (p<0.05) activity.Conclusion: It is concluded that O. bracteatum possesses significant central and peripheral analgesic activity in animal model.Bangladesh Journal of Medical Science Vol.17(1) 2018 p.36-41

Optimal interval for hot water immersion tail-flick test in rats

2013 ◽  
Vol 26 (4) ◽  
pp. 218-222 ◽  
Author(s):  
Quanhong Zhou ◽  
Yuhua Bao ◽  
Xin Zhang ◽  
Lulu Zeng ◽  
Li Wang ◽  
...  
Keyword(s):  
Water Immersion ◽  
Hot Water ◽  
Male Rats ◽  
Laboratory Animals ◽  
Control Group ◽  
Tail Flick ◽  
Sprague Dawley ◽  
Tail Flick Test ◽  
Optimal Interval ◽  
Hot Water Immersion

BackgroundThe hot water tail-flick test is widely used to measure the degree of nociception experienced by laboratory animals. This study was carried out to optimise interval times for the hot water immersion tail-flick tests in rats.MethodTen different intervals from 10 s to 1 h were tested in 60 Sprague–Dawley male rats. At least eight rats were tested for each interval in three consecutive hot water tail-flick tests. Dixon's up-and-down method was also used to find the optimal intervals. The same rats were then divided into two groups. In Group N, naloxone was injected to reverse the prolonged latency times, whereas saline was used in the control Group S.ResultsIntervals of 10 s, 20 s, 30 min and 1 h did not significantly impact latencies, yielding similar results in three consecutive tests (p> 0.05). However, interval times of between 30 s and 20 min, inclusively, caused significantly prolonged latencies in the second and third tests (p< 0.001). Dixon's up-and-down method showed that 95% of the rats had prolonged latencies in hot water tail-flick tests at intervals longer than 32 s. Naloxone reversed prolonged latencies in Group N, whereas the latencies in Group S were further prolonged in 5 min interval tests.ConclusionThe optimal intervals for hot water tail-flick tests are either shorter than 20 s or longer than 20 min. The prolonged latencies after repetitive tests were attributable to an endocrine opioid.

Effects of Radolmidine, A Novel α2-Adrenergic Agonist Compared with Dexmedetomidine in Different Pain Models in the Rat

2000 ◽  
Vol 93 (2) ◽  
pp. 473-481 ◽  
Author(s):  
Mei Xu ◽  
Vesa K. Kontinen ◽  
Eija Kalso
Keyword(s):  
Neuropathic Pain ◽  
Antinociceptive Effect ◽  
Thermal Hyperalgesia ◽  
Pharmacokinetic Profile ◽  
Intrathecal Administration ◽  
Tail Flick ◽  
Sprague Dawley ◽  
Tail Flick Test ◽  
Alpha2 Adrenoceptor ◽  
Carrageenan Inflammation

Background Intrathecally administered alpha2-adrenoceptor agonists produce effective antinociception, but sedation is an important adverse effect. Radolmidine is a novel alpha2-adrenoceptor agonist with a different pharmacokinetic profile compared with the well-researched dexmedetomidine. This study determined the antinociceptive and sedative effects of radolmidine in different models of acute and chronic pain. Dexmedetomidine and saline served as controls. Methods Male Sprague-Dawley rats were studied in acute pain (tail flick), carrageenan inflammation, and the spinal nerve ligation model of neuropathic pain. Mechanical allodynia was assessed with von Frey filaments, cold allodynia with the acetone test, and thermal hyperalgesia with the paw flick test. Locomotor activity-vigilance was assessed in a dark field. Dexmedetomidine and radolmidine were administered intrathecally in doses of 0.25 microg, 2.5 microg, 5 microg, and 10 microg. Results In the tail flick test, radolmidine showed a dose-dependent antinociceptive effect, being equipotent compared with dexmedetomidine. In carrageenan inflammation, intrathecal doses of 2.5 microg or 5 microg of dexmedetomidine/radolmidine produced significant antinociception compared with saline (P &lt; 0.01). The two drugs were equianalgesic. In the neuropathic pain model, an intrathecal dose of 5 microg dexmedetomidine-radolmidine had a significant antiallodynic effect compared with saline (P &lt; 0.01). The two drugs were equipotent. Intrathecal administration of both dexmedetomidine and radolmidine dose dependently decreased spontaneous locomotor acitivity-vigilance, but this effect was significantly smaller after intrathecal administration of radolmidine than after intrathecal dexmedetomidine. Conclusions Radolmidine and dexmedetomidine had equipotent antinociceptive effects in all tests studied. However, radolmidine caused significantly less sedation than dexmedetomidine, probably because of a different pharmacokinetic profile.

scholarly journals Alteration in behavior of rat after chronic exposure to acetamiprid

2019 ◽  
Vol 12 (2) ◽  
pp. 254-257 ◽  
Author(s):  
Samiran Mondal ◽  
Saktipada Pradhan ◽  
Sunit K. Mukhopadhayay
Keyword(s):  
Treated Group ◽  
Control Group ◽  
Tail Flick ◽  
Formalin Injection ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Tail Flick Test ◽  
Group Iii ◽  
Multiple Exposures ◽  
Group I

Background and Aim: Acetamiprid is a chemical of neonicotinoid group which binds with nicotinic acetylcholine receptor (nAChR) and alters the brain function. The present study was taken up to enlight the understanding of nociception behavior in Sprague Dawley (SD) rat after multiple exposures to acetamiprid. Materials and Methods: For experiment purpose, a total of 48 SD rats were divided into four dose groups having 12 animals each. Group I was control group received only distilled water. Group II, Group III, and Group IV were treated with acetamiprid at a dose rate of 5, 20, and 40 mg/kg body weight, respectively. Rats were tested in induced pain by formalin injection and tail flick test. Results: The flinch counts in formalin-induced pain in acetamiprid-treated rat were reduced in a dose-dependent manner, whereas, in tail flick test, no such altered pain behavior was observed in treated group compared to control animals. Conclusion: Acetamiprid alters the centralized nociception through nAChR but could not trigger the associated signal to inhibit the nociception peripherally.

scholarly journals Effect of intrathecal oxcarbazepine on rat tail flick test-determined morphine tolerance

2009 ◽  
Vol 57 (3) ◽  
pp. 337
Author(s):  
In-Gu Jun ◽  
Jong-Yeon Park ◽  
Yun-Sik Choi ◽  
So-Hyun Im
Keyword(s):  
Morphine Tolerance ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Rat Tail

Suppressing HMGB1-TLR4-Mediated Neuroinflammation Alleviates Morphine Tolerance via Inhibiting AMPK-HO-1 Pathway in The Spinal Cord of Mice

2020 ◽  
Author(s):  
Tong-Tong Lin ◽  
Lei Sheng ◽  
Li Wan ◽  
Lu-Lu Ji ◽  
Jin-Can Li ◽  
...  
Keyword(s):  
Western Blot ◽  
Cell Line ◽  
High Mobility ◽  
Morphine Tolerance ◽  
Nuclear Factor Κb ◽  
Immunofluorescence Staining ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Analgesic Tolerance ◽  
Microglial Cell Line

Abstract Background and objectives: A major unresolved issue in treating pain is the analgesic tolerance produced by opioids. Neuroinflammation was thought to be important in the development of morphine tolerance. The role of High mobility group box-1 (HMGB1) in morphine tolerance is elusive. Methods: ICR mice were used for tail-flick test to evaluate morphine tolerance. SD rats were used to collect the CSF to investigate whether morphine could induce the efflux of HMGB1 into extracellular environment. The neural cell line SH-SY5Y and the microglial cell line BV-2 were used to investigate the pharmacological effects and the mechanism of morphine-induced neuroinflammation. The activation of microglia was assessed by immunofluorescence staining. Neuroinflammation-related cytokines were measured by western blot and real-time PCR. The level of HMGB1 and related signaling pathway were evaluated by western blot and immunofluorescence staining.Results: Morphine induces the release of HMGB1 from neurons. The released HMGB1 activated microglia and triggered TLR4-mediated inflammatory response, leading to the phosphorylation of nuclear factor-κB (NF-κB) p65 and the upregulation of IL-1β. The secretion of HMGB1 was under the control of AMPK-HO-1 pathway. AMPK inhibitor and HO-1 inhibitor inhibited the release of HMGB1 and suppressed HMGB1-TLR4 mediated neuroinflammation.Conclusion: Our study indicated that morphine-induced extracellular HMGB1 was critical for morphine tolerance. The release of HMGB1 was regulated by AMPK-HO-1 pathway. Our findings may represent a bright prospect for the improvement of morphine tolerance with HMGB1 inhibitor and/or the inhibitors for AMPK-HO-1 axis.

scholarly journals Effects ofBrugmansia arboreaExtract and Its Secondary Metabolites on Morphine Tolerance and Dependence in Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Laura Mattioli ◽  
Antonio Bracci ◽  
Federica Titomanlio ◽  
Marina Perfumi ◽  
Vincenzo De Feo
Keyword(s):  
Secondary Metabolites ◽  
Therapeutic Potential ◽  
Morphine Tolerance ◽  
Opioid Addiction ◽  
Withdrawal Symptoms ◽  
Morphine Dependence ◽  
Tail Flick ◽  
Tail Flick Test

The aim of the present study was to investigate,in vivo, the effect of aBrugmansia arboreaextract (BRU), chromatographic fractions (FA and FNA), and isolated alkaloids on the expression and the acquisition of morphine tolerance and dependence. Substances were acutely (for expression) or repeatedly (for acquisition) administered in mice treated with morphine twice daily for 5 or 6 days, in order to make them tolerant or dependent. Morphine tolerance was assessed using the tail-flick test at 1st and 5th days. Morphine dependence was evaluated through the manifestation of withdrawal symptoms induced by naloxone injection at 6th day. Results showed that BRU significantly reduced the expression of morphine tolerance, while it was ineffective to modulate its acquisition. Chromatographic fractions and pure alkaloids failed to reduce morphine tolerance. Conversely BRU, FA, and pure alkaloids administrations significantly attenuated both development and expression of morphine dependence. These data suggest thatBrugmansia arboreaLagerh might have human therapeutic potential for treatment of opioid addiction.

Paroxetine effects on morphine analgesic tolerance in rats

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Navideh Sahebi Vaighan ◽  
Soha Parhiz ◽  
Masoumeh Sabetkasaei ◽  
Taraneh Moini Zanjani ◽  
Malek Zarei
Keyword(s):  
Intraperitoneal Injection ◽  
Tolerance Induction ◽  
Morphine Tolerance ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Analgesic Tolerance ◽  
Progressive Decline ◽  
Morphine Administration ◽  
Male Wistar Rats ◽  
Daily Intraperitoneal Injection

Abstract Objectives To alleviate different pain intensities, morphine administration has been extensively used. However, prolonged administration of morphine leads to a progressive decline of its analgesic effect which limits their overall utility. Morphine tolerance is considered as a challenging issue for the treatment of both acute and chronic pain. We conducted this study in rats to investigate the effect of paroxetine on morphine tolerance when used preemptively or after morphine tolerance had developed. Methods Male Wistar rats (weight 250–300 g, n=10) were used to evaluate the effects of paroxetine on tolerance to morphine. In order to induce tolerance, daily intraperitoneal injection of morphine (7 mg/kg) was done. After tolerance induction, a group of animals received intraperitoneal injection of 10 mg/kg paroxetine 30 min prior to each morphine dose. In another trial, to investigate the potential of paroxetine to prevent tolerance to morphine, animals were pretreated with 10 mg/kg paroxetine 30 min before morphine administration. In the control groups, 10 mL/kg of saline was injected. The behavioral test (tail-flick test) was done for all groups. Results Our data showed that paroxetine significantly reversed tolerance to morphine when used after tolerance induction (p<0.001). However, administration of paroxetine before occurrence of tolerance had no effect. Conclusions We conclude that paroxetine could decrease tolerance to morphine when used after the occurrence of morphine tolerance, while it was not able to prevent morphine tolerance when administered preemptively. Ethical committee number IRIB.SBMU.MSP.REC.1394.098.

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