Tail-immersion Test In Rats Research Articles

Involvement of serotonergic, noradrenergic and gabaergic systems in the antinociceptive effect of a ketamine-magnesium sulfate combination in acute pain

Abstract Ketamine and magnesium can interact in additive, supra-additive and antagonistic manners in analgesia or anesthesia. Ketamine is a non-competitive NMDA receptor antagonist. Magnesium is an endogenous non-competitive NMDA antagonist that causes anion channel blockade in a dose-dependent manner. It has been established that ketamine and magnesium interact synergistically in the tail-immersion test in rats. To determine the role of serotonergic, GABAergic and noradrenergic systems in analgesia induced by the ketamine-magnesium sulfate combination. Experiments were performed on male Wistar albino rats (200-250 g). Antinociception was evaluated by the tail-immersion test. Methysergide (0.5 and 1 mg/kg, sc) administered alone did not affect nociception in rats. Methysergide (0.5 and 1 mg/kg, sc) antagonized the antinociceptive effect of the ketamine (5 mg/kg)-magnesium sulfate (5mg/kg) combination. Bicuculline (0.5 and 1 mg/kg, sc) given alone did not change the threshold to thermal stimuli in rats. Bicuculline (0.5 and 1 mg/kg, sc) antagonized the antinociceptive effect of the ketamine (5 mg/kg)-magnesium sulfate (5 mg/kg) combination. Yohimbine (0.5, 1 and 3 mg/kg, sc) applied alone did not change nociception. Yohimbine at a dose of 0.5 mg/kg did not influence the effect of ketamine (5 mg/kg)-magnesium sulfate (5 mg/kg), while yohimbine at doses of 1 and 3 mg/kg antagonized the antinociceptive effect of this combination. Serotonergic, noradrenergic and GABAergic systems participate, at least in part, in the antinociceptive effect of the ketamine-magnesium sulfate combination in acute pain in rats.

Study of the interactions between magnesium, ketamine and morphine on acute nociception in rats

ObjectivesStudy is aimed at evaluating the effects of ketamine and magnesium sulphate on acute nociceptive pain in rats and examination whether magnesium sulfate added to ketamine or morphine-ketamine combination produces higher level of analgesia.MethodsAnalgesic activity was assessed by tail-immersion test in male Wistar rats (200–250 g).ResultsMagnesium sulfate (2.5–60 mg/kg, s.c.) and ketamine (2.5-30 mg/kg, i.p.) given alone did not produce any effect on antinociception. However, there is a synergistic interaction between ketamine (2.5, 5 and 10 mg/kg) and magnesium sulfate (5 mg/kg). Both ketamine and magnesium sulfate, as well as their combination potentiated the antinociceptive effect of morphine (2.6 mg/kg, i.p.).ConclusionThis study revealed potentiation of ketamine and morphine-ketamine combination by magnesium sulphate in tail-immersion test in rats with higher activity when ketamine is given before magnesium sulfate. It is first time to demonstrate the synergistic interaction between magnesium sulphate and ketamine in lowering body temperature and in antinociception with statistical confirmation.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Efficacy of the morphine–ketamine–magnesium sulphate combination in the tail-immersion test in rats

Efficacy of the morphine–ketamine–magnesium sulphate combination in the tail-immersion test in rats

Analgesic, Antipyretic and Anti-inflammatory Activities of the Egyptian Spitting Cobra; Naja nubiae Venom

Objectives: Although many venomous snakes represent a potential human health threat, their venoms provide a rich source of active components, many of which have been recently identified, and used as potential candidates for pharmacological therapeutic purposes. The current study was designed to evaluate the analgesic, antipyretic and antiinflammatory activities of the Egyptian spitting cobra Naja nubiae venom. Methods: The venom of N. nubiae was intraperitoneally injected at two dose levels (1/10 and 1/5 LD50). The peripheral and central analgesic effects were examined using acetic acidinduced abdominal writhing in mice and tail immersion test in rats, respectively. Brewer’s yeast-induced pyrexia in rats was carried out to determine the antipyretic activity of the same doses, whereas the anti-inflammatory activity was tested using carrageenan-induced paw edema in mice. Results: The results showed that N. nubiae venom produced a significant analgesic activity in acetic acid-induced abdominal constriction response in mice and thermal nociception in rat. Moreover, the venom revealed a significant antipyretic effect on yeast-induced pyrexia. In paw edema, venom exhibited a significant activity with a maximum percentage of inhibition reaching 60.1% on both doses after 5 hour treatment, which was more powerful when compared with the standard drug; diclofenac sodium (38.6%). Histologically, the venom induced a moderate inflammatory cells infiltration in the dermis of paw. Conclusion: These results suggest potential analgesic, antipyretic, and anti-inflammatory activities of the Egyptian spitting cobra crude venom.

Antinociceptive activity of fruits extracts and “arrope” of Geoffroea decorticans (chañar)

Ethnopharmacological relevanceGeoffroea decorticans (chañar) fruits and their derivate product (arrope) have been traditionally used as food and a folk medicine for the treatment of a wide variety of diseases including bronchopulmonary disorders and to relieve dolorous process. Aim of the studyIn order to evaluate the pharmacology action of this plant, studies were performed of antinociceptive and antioxidant activities. Materials and methodsThe aqueous and ethanolic extracts and arrope of chañar were evaluated in various established pain models, including chemical nociception induced by subplantar formalin and intraperitoneal acetic acid and thermal nociception method, such as tail immersion test in rats. To examine the possible connection of the opioid receptor to the antinociceptive activity of extracts and arrope it was performed a combination test with naloxone, a non-selective opioid receptor antagonist. ResultsThe aqueous extract and arrope (1000mg/kg) caused an inhibition of the pain in formalin test in the first phase, similar to morphine and decrease in the second phase. In a combination test using naloxone, diminished analgesic activity of aqueous extract and arrope were observed, indicating that antinociceptive activity is connected with the opioid receptor. The aqueous extract and arrope, caused an inhibition of the writhing response induced by acetic acid. Central involvement in analgesic profile was confirmed by the tail immersion test, in which the aqueous extract and arrope showed a significant analgesic activity by increasing latency time. The aqueous extract showed higher antioxidant activity than the arrope, it may be due to the cooking process. ConclusionsThis study has shown that the aqueous extract and arrope of Geoffroea decorticans (chañar) fruits, does possess significant antinociceptive effects. It is further concluded that aqueous extract with maximum inhibition of free radical is the most potent extract amount tested extracts. At the oral doses tested the aqueous extract and arrope were non-toxic. The present results justifies their popular use and constitutes the first validation study of the antinociceptive action.

Antinociceptive effects of two deltorphins analogs in the tail-immersion test in rats

The antinociceptive effects of analogs of deltorphins: cyclo(Nδ,Nδ-carbonyl-d-Orn2, Orn4)deltorphin (DEL-6) and deltorphin II N-(ureidoethyl)amide (DK-4) after intracerebroventricular (i.c.v.) administration were investigated in the tail-immersion test in rats. Morphine, the most commonly used μ-opioid receptors (MOR) agonist, was employed as a reference compound. The contribution of the MOR, δ-(DOR) and κ-opioid receptors (KOR) in antinociceptive effects of the deltorphins analogs was studies using selective antagonists of these receptors. The results indicated that DK-4 (5, 10 and 20nmol) and DEL-6 (5, 10 and 20nmol) were the most effective in alleviating thermal pain at the dose of 20nmol. The antinociceptive potency of DEL-6 at the dose of 20nmol was approximately equal but DK-4 at the dose of 20nmol was less effective than morphine at the dose of 13nmol. DOR antagonist – naltrindole (NTI, 5nmol) very strongly and, to the lower extent MOR antagonist – β-funaltrexamine (β-FNA, 5nmol), inhibited antinociceptive effect of DK-4 (20nmol). In turn, β-FNA was more potent than NTI in inhibition of the antinociceptive effects of DEL-6. Co-administration of DEL-6 and morphine at doses of 5nmol, which do not produce measurable antinociception, generated additive antinociceptive effect. Chronic intraperitoneal (i.p.) injection of morphine (9 days) displayed a marked analgesic tolerance to the challenge dose of morphine and a slight cross-tolerance to challenge doses of DEL-6 and DK-4, given i.c.v. These findings indicate that the new deltorphin analogs recruit DOR and MOR to attenuate the nociceptive response to acute thermal stimuli.

Pharmacological and toxicity studies of the crude extracts and fractions of Hedranthera barteri leaf in rats and mice

This study assessed the anti-nociceptive and anti-inflammatory potency of the hydro-ethanol extract and fractions from Hedranthera barteri leaf. Column chromatography of the crude extracts, practical acute toxicity testing and fixed dose procedures were carried out. Effects of the extracts on nociception were assessed by tail immersion test in rats, formalin-induced paw licking in rats and acetic acid-induced writhing in mice. The effect of the extracts on inflammation was assessed by carrageenan-induced paw oedema in rats. The hydro-ethanol extracts of Hedranthera barteri reduced nociception and inflammation in a dose-dependent manner. SNG 1, SNG 2 and SNG 3 were separated from the ethanol fractions. The spectra of the compound suggest the presence of a fatty compound, β-sitosterol, as an anti-nociceptive and antiinflammatory compound that may be present in the leaf of the plant.(Afr. J. Biomed. Res. 11: 311 - 321)Key Words: Hedranthera barteri, nociception, inflammation, toxicity, β-sitosterol

Cryptic peptide derived from the rat neuropeptide FF precursor affects G-proteins linked to opioid receptors in the rat brain

Recently, we reported the discovery of a novel amino acid sequence derived from the NPFF precursor NAWGPWSKEQLSPQA, which blocked the expression of conditioned place preference induced by morphine and reversed the antinociceptive activity of morphine (5 mg/kg, s.c.) in the tail-immersion test in rats. Here, we name it as NPNA (Neuropeptide NA from its flanking amino acid residues). The synthetic peptide influenced the expression of mRNA coding for Gα(i1), (i2), and (i3) subunits. The results provide further evidence that yet another bioactive sequence might be present within the NPFF precursor.

A novel cryptic peptide derived from the rat neuropeptide FF precursor reverses antinociception and conditioned place preference induced by morphine

Neuropeptide FF (NPFF) precursors from different species contain at least three known neuropeptides, i.e. FF (FLFQPQRF-NH 2), AF (AGEGLSSPFWSLAAPQR-NH 2) and SF (SLAAPQRF-NH 2). We demonstrate that the rat NPFF precursor contains another bioactive sequence, NAWGPWSKEQLSPQA, spanning between positions 85 and 99. Synthetic NPFF precursor (85–99) (10 and 20 nmol, i.c.v.) blocked the expression of conditioned place preference induced by morphine (5 mg/kg, s.c.). This peptide alone (10 and 20 nmol, i.c.v.) had no influence on the baseline latency of a nociceptive reaction but reversed the antinociceptive activity of morphine (5 mg/kg, s.c.) in the tail-immersion test in rats. These data suggest the existence of a novel bioactive cryptic peptide within an already known NPFF precursor.

Methysergide and metergoline reduce morphine analgesia with no effect on the development of tolerance in rats.

A single subcutaneous injection of 5 mg/kg metergoline or 10 mg/kg methysergide, two serotonin antagonists, or 1 mg/kg naloxone, significantly reduced the effect of a subcutaneous dose of 3 mg/kg morphine in the tail immersion test in rats. The same drugs and doses were administered concurrently with 10 mg/kg morphine twice daily for 3 days and nociceptive responses were measured 96 h later. Tolerance to the effect of 3 mg/kg morphine was comparable in animals which had received vehicle + morphine or serotonin antagonists + morphine, whereas naloxone completely prevented the development of tolerance. The results argue against a role of serotonin in the development of tolerance to the antinociceptive effect of morphine and suggest it may be possible to dissociate morphine analgesia from tolerance development, at least in the conditions used in the present study.