Analgesic Interaction Between Morphine with Fentanyl In Experimental Murine Pain

Abstract Opioids are among the most effective pain relievers available, however multimodal antinociception between opioids, has not been extensively studied in diverse animal pain models.In this study the pharmacological interaction of morphine with fentanyl was evaluated in different murine pain models by means of isobolographic analysis. In control animals, morphine and fentanyl produced a dose-related antinociceptive action in the murine assays and the rank of potency was: formalin hind paw phase I > formalin phase II > tail flick. Coadministration of morphine with fentanyl, in a fixed relation 1:1 of their ED50, produces a dose response in all tests and the isobologram resulted in synergism. Fentanyl was more effective than morphine which could be explained according the suggestion that opioids could be acting through other targets, with different binding capacity thru the regulation or activation of non-opioid receptors. Co-administration of morphine with fentanyl induces synergism in all murine trials, confirming the antinociceptive capacity of both opioids which would constitute a promisory idea to multimodal treatment of pain.

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An isobolographic analysis of the anti-nociceptive effect of geraniin in combination with morphine or diclofenac

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2017-0031 ◽

2018 ◽

Vol 29 (2) ◽

pp. 201-209 ◽

Cited By ~ 4

Author(s):

Eric Boakye-Gyasi ◽

Ella Anle Kasanga ◽

Elvis Ofori Ameyaw ◽

Wonder Kofi Mensah Abotsi ◽

Robert Peter Biney ◽

...

Keyword(s):

Phase I ◽

Phase Ii ◽

Aqueous Extract ◽

Dose Response ◽

Formalin Test ◽

Fixed Ratio ◽

Test Dose ◽

Response Curves ◽

Isobolographic Analysis ◽

Aerial Parts

AbstractBackground:Geraniin, a dehydroellagitannin, is a major component of the aqueous extract of the aerial parts ofPhyllanthus muellerianus(Kuntze) Exell. (Euphorbiaceae). SeveralPhyllanthusspecies are traditionally used for painful disorders. The anti-nociceptive effects of the aqueous extract of the aerial parts ofP. muellerianusand of geraniin have been scientifically established. The aim of the paper is to determine whether a combination of geraniin and diclofenac or geraniin and morphine leads to better anti-nociceptive effects.Methods:The nature of the interactions of morphine and diclofenac with geraniin was evaluated by undertaking the isobolographic analysis. Mice were treated with geraniin (3–30 mg/kg), morphine (1–10 mg/kg), and diclofenac (10–100 mg/kg) to obtain the ED50values of the agents in the formalin test. Dose-response curves were then obtained and analyzed after the co-administration of geraniin with morphine or diclofenac in fixed ratio (1:1) combinations based on specific fractions (1/2, 1/4, and 1/8) of their respective ED50values for the formalin test.Results:Geraniin was less potent than morphine but more potent than diclofenac in the formalin-induced nociception. The isobolographic analysis of geraniin/morphine (G/M) and geraniin/diclofenac combinations (G/D) at different fractions revealed the potentiation of their anti-nociceptive effects. The degrees of potentiation, which were calculated as interaction indices, showed synergism for both combinations in both phase I (G/M: 0.040, G/D: 0.017) and phase II (G/M: 0.004, G/D: 0.002) of the formalin test.Conclusions:The present study demonstrates synergism for the co-administration of geraniin with both morphine and diclofenac.

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5 ANIMAL PAIN MODELS AND DRUG DISCOVERY

European Journal of Pain Supplements ◽

10.1016/s1754-3207(11)70006-2 ◽

2011 ◽

Vol 5 (S1) ◽

pp. 2-2

Author(s):

A. Eschalier

Keyword(s):

Drug Discovery ◽

Animal Pain ◽

Pain Models

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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

Journal of Neurosciences in Rural Practice ◽

10.4103/0976-3147.83577 ◽

2011 ◽

Vol 02 (02) ◽

pp. 130-136 ◽

Cited By ~ 9

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.

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NSAID Antinociception Measured in a Chemical and a Thermal Assay in Mice

Pain Research and Management ◽

10.1155/2001/701427 ◽

2001 ◽

Vol 6 (4) ◽

pp. 190-196 ◽

Cited By ~ 13

Author(s):

HF Miranda ◽

J Lopez ◽

F Sierralta ◽

A Correa ◽

G Pinardi

Keyword(s):

Dose Response ◽

Intrathecal Administration ◽

Test Subject ◽

Tail Flick ◽

Response Curves ◽

Tail Flick Test ◽

Chemical Test ◽

Writhing Test ◽

Nociceptive Stimulus ◽

Dose Response Curves

The antinociceptive activity of several nonsteroidal anti-inflammatory drugs (NSAIDs) that were administered either intraperitoneally or intrathecally was assessed in mice by two algesiometric tests. The first was the writhing test, which assessed the abdominal constrictions that were induced by intraperitoneal acetic acid (a chemical test), and the second was the tail flick test, which measured pain responses to heat stimuli. The corresponding effective doses and their relative potencies were compared because these tests use different nociceptive stimuli with different transmission pathways. The intraperitoneal and intrathecal dose-response curves for the antinociception induced by every NSAID that was tested were parallel in the writhing test. In the tail flick test, however, only the intraperitoneal and intrathecal dose-response curves for ketoprofen, piroxicam, naproxen, nimesulide, paracetamol and diclofenac were parallel. The results obtained in this study confirm that NSAIDs possess different abilities to induce inhibition of cyclooxygenase, and they can be indirectly assessed by their different antinociceptive activities, depending on the algesiometric assays that are used. The antinociception of most NSAIDs might involve central mechanisms. The findings demonstrate the increasing importance of the spinal cord in processing and modulating nociceptive input, because intrathecal administration of NSAIDs is always more effective (in terms of potency) than systemic administration; thus, the antinociceptive efficacy of NSAIDs strongly depends on the algesiometric assay that is used and on the type of the nociceptive stimulus to which the test subject is exposed.

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Involvement of NO in Antinociception of NSAIDS in Murine Formalin Hind Paw Assay

Drug Research ◽

10.1055/a-1095-5418 ◽

2020 ◽

Vol 70 (04) ◽

pp. 145-150 ◽

Cited By ~ 2

Author(s):

Viviana Noriega ◽

Hugo F. Miranda ◽

Juan Carlos Prieto ◽

Ramón Sotomayor-Zárate ◽

Fernando Sierralta

Keyword(s):

Phase I ◽

Phase Ii ◽

Dose Response ◽

Rank Order ◽

Linear Regression Analysis ◽

Second Phase ◽

Response Curves ◽

Before And After ◽

Two Phases ◽

Phase Phase

AbstractThere are different animal models to evaluate pain among them the formalin hind paw assay which is widely used since some of its events appear to be similar to the clinical pain of humans. The assay in which a dilute solution of formalin is injected into the dorsal hindpaw of a murine produces two ‘phases’ of pain behavior separated by a inactive period. The early phase (Phase I) is probably due to direct activation of nociceptors and the second phase (Phase II) is due to ongoing inflammatory input and central sensitization. Mice were used to determine the potency antinociceptive of piroxicam (1,3,10,and 30 mg/kg), parecoxib (0.3, 1,3,10 and 30 mg/kg), dexketoprofen (3,10,30 and 100 mg/kg) and ketoprofen (3,10,30 and 100 mg/kg). Dose-response for each NSAIDs were created before and after 5 mg/kg of L-NAME i.p. or 5 mg/kg i.p. of 7-nitroindazole. A least-squares linear regression analysis of the log dose–response curves allowed the calculation of the dose that produced 50% of antinociception (ED50) for each drug. The ED50 demonstrated the following rank order of potency, in the phase I: piroxicam > dexketoprofen > ketoprofen > parecoxib and in the phase II: piroxicam > ketoprofen > parecoxib > dexketoprofen. Pretreatment of the mice with L-NAME or 7-nitroindazol induced a significant increase of the analgesic power of the NSAIDs, with a significant reduction of the ED50. It is suggested that NO may be involved in both phases of the trial, which means that nitric oxide regulates the bioactivity of NSAIDs.

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Is Hippocampus Susceptible to Antinociceptive Tolerance to NSAIDs Like the Periaqueductal Grey?

Pain Research and Treatment ◽

10.1155/2014/654578 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Nana Tsiklauri ◽

Ivliane Nozadze ◽

Gulnazi Gurtskaia ◽

Merab G. Tsagareli

Keyword(s):

Dorsal Hippocampus ◽

Antinociceptive Effect ◽

Male Rats ◽

Opioid Antagonist ◽

Tail Flick ◽

Pain Models ◽

Inflammatory Drugs ◽

Antinociceptive Tolerance ◽

Undesirable Feature

Emotional distress is the most undesirable feature of painful experience. Numerous studies have demonstrated the important role of the limbic system in the affective-motivational component of pain. The purpose of this paper was to examine whether microinjection of nonsteroidal anti-inflammatory drugs (NSAIDs), Clodifen, Ketorolac, and Xefocam, into the dorsal hippocampus (DH) leads to the development of antinociceptive tolerance in male rats. We found that microinjection of these NSAIDs into the DH induces antinociception as revealed by a latency increase in the tail-flick (TF) and hot plate (HP) tests compared to controls treated with saline into the DH. Subsequent tests on consecutive three days, however, showed that the antinociceptive effect of NSAIDs progressively decreased, suggesting tolerance developed to this effect of NSAIDs. Both pretreatment and posttreatment with the opioid antagonist naloxone into the DH significantly reduced the antinociceptive effect of NSAIDs in both pain models. Our data indicate that microinjection of NSAIDs into the DH induces antinociception which is mediated via the opioid system and exhibits tolerance.

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Co-administration of Pregabalin and Curcumin Synergistically Decreases Pain-Like Behaviors in Acute Nociceptive Pain Murine Models

Molecules ◽

10.3390/molecules25184172 ◽

2020 ◽

Vol 25 (18) ◽

pp. 4172

Author(s):

Sarinee Leksiri ◽

Hasriadi Hasriadi ◽

Peththa Wadu Dasuni Wasana ◽

Opa Vajragupta ◽

Pornchai Rojsitthisak ◽

...

Keyword(s):

Acetic Acid ◽

Area Under The Curve ◽

Synergistic Interaction ◽

Nociceptive Pain ◽

Fixed Dose ◽

Tail Flick ◽

Dose Ratio ◽

Tail Flick Test ◽

Analgesic Effects ◽

Pain Models

Analgesic drugs in a combination-form can achieve greater efficacy with lesser side effects compared to either drug alone. The combination of drugs acting at different targets or mechanisms of action has been recognized as an alternative approach for achieving optimal analgesia. In this study, the analgesic effects of pregabalin (30, 60, 100, 200 mg/kg), curcumin (15, 30, 60, 100, 120 mg/kg), and 1:1 fixed-dose ratio of the pregabalin-curcumin combination were assessed using two acute nociceptive pain models, the acetic acid-induced writhing and tail-flick tests in mice. The pregabalin-curcumin combination produced a dose-dependent decrease in mean of writhes and an increase in the percentage of antinociception by the acetic acid-induced writhing test. In the tail-flick test, the combination also showed an improvement in antinociception indicated by the tail-flick latency, % antinociception, and area under the curve (AUC). Isobolographic analysis of interactions demonstrated a significant synergistic interaction effect between pregabalin and curcumin in both acute nociceptive pain models with the experimental ED50 below the predicted additive line and the combination index < 1. These findings demonstrate that the combination of pregabalin and curcumin exhibits a synergistic interaction in mouse models of acute nociceptive pain.

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