Tail Immersion Test Research Articles

Anti-nociceptive and Anti-inflammatory Activities of Crotalaria pallida Aiton (Fam: Fabaceae) Leaves

The present study was designed to evaluate the anti-nociceptive and anti-inflammatory properties of the ethanolic extract of Crotalaria pallida Aiton (Family: Fabaceae) leaves based on its traditional uses in the treatment of urinary disorders, external application as a poultice to treat painful swelling of joints and to reduce fever. The anti-nociceptive effect was assessed in mice using acetic acidinduced writhing, formalin-induced paw licking and tail immersion assays. Anti-inflammatory activity was evaluated by carrageenan induced paw oedema in rats. In acetic acid-induced writhing test, the extract at different doses (50 mg/kg and 100 mg/kg bw) significantly (p<0.001) and dose-dependently reduced pain by 37.50% and 47.70%, respectively. The extract also significantly inhibited formalininduced paw licking in mice at both the early and late phases. In the tail immersion test, the extract caused a significant inhibition of pain (64.91% inhibition after 4 hrs) at a dose of 100 mg/kg. C. pallida exhibited a considerable inhibition of paw oedema development in the carrageenan-induced oedema test. The findings of the study suggested that C. pallida leaves have significant anti-nociceptive and antiinflammatory effects, confirming the traditional uses of this plant in the treatment of various diseases associated with pain and inflammation.Bangladesh Pharmaceutical Journal 20(2): 165-171, 2017

αCGRP Transgenic Mice Display Typical Physiologic Features

Calcitonin gene-related peptide (CGRP) plays an important role in several physiological processes such as vasodilation, cardiovascular homeostasis and transmission of pain. Here we report the generation of a transgenic mouse overexpressing αCGRP and the impact of this on baseline physiological responses. αCGRP transgenic mice displayed significantly increased αCGRP mRNA levels in the kidney, heart and hippocampus. To assess cardiovascular physiology, we measured arterial pressure using a tail cuff system. Heart rate, systolic pressure, mean arterial pressure and diastolic pressure were significantly lower in αCGRP transgenic mice than wild-type mice. To assess pain, a hot plate test was performed and the latency of response was used as an indicator of supraspinal response. In addition, a tail immersion test was performed to assess thermal nociception. A significant increase in latency was observed in the αCGRP transgenic mice when compared with wild-type mice in both tests. These results suggest that αCGRP overexpression causes an increase in thermal reaction and downregulation of the cardiovascular system, presumably due in increased levels of αCGRP.

Down-regulation of telomerase reverse transcriptase-related anti-apoptotic function in a rat model of acrylamide induced neurobehavioral deficits

Although the precise mechanism is unknown, neuron apoptosis is believed to participate in neuropathy caused by acrylamide (ACR). Telomerase reverse transcriptase (TERT) exhibits an anti-apoptotic function, but its contribution to the pathogenesis of ACR neurotoxicity is unclear. We investigated adult male rats that were given 30, 40 and 50 mg/kg ACR three times/week for 4 weeks. We found that ACR treatment caused significant deficits in sensory/motor function as measured by gait score, landing foot spread distance, movement initiation test and tail immersion test. Histological examination showed that the cerebral cortex in all ACR treated animals exhibited fewer neurons and more condensed nuclei than normal cortex. A significant increase in apoptosis was found in the cerebral cortex of rat brains subjected to ACR treatment in a dose-dependent manner. The expression of TERT in the brain was significantly reduced by ACR treatment. The pro-apoptotic cleaved caspase-3 protein level was increased, while the anti-apoptotic Bcl-2 protein level was decreased by 30 − 50 mg/kg ACR. Our findings indicate that TERT and its downstream regulators of neuron apoptosis, including Bcl-2 and cleaved caspase-3, were involved in ACR neurotoxicity.

Monosodium glutamate induced nociception and oxidative stress dependent on time of administration, age of rats and susceptibility of spinal cord and brain regions

Monosodium glutamate (MSG), a food flavor enhancer used worldwide, has been studied because it may cause neurotoxicity, which is associated with oxidative stress. The aim of this study was to investigate whether spinal cord and brain regions are affected by oxidative stress and the temporal profile of nociceptive responses induced by MSG in newborn and adult rats. The newborn (post natal day, PND 1) Wistar rats received ten subcutaneous injections of MSG (4.0 g/kg) or saline solution. At PND 3, 11 or 90, the rats performed nociceptive tests and parameters of oxidative stress were evaluated in samples of spinal cord and brain regions. Adult rats (PND 90) were injected with MSG (4.0 g/kg, 10 injections) or saline solution, but MSG did not induce nociception or oxidative stress. The neonatal administration of MSG increased nociceptive behavior in the tail immersion, hot plate and formalin tests and decreased the SOD activity in spinal cord of PND 3 rats. In rats at PND 11 and 90, the neonatal administration of MSG increased mechanical allodynia and nociceptive behavior in the hot plate and formalin tests. The neonatal administration of MSG induced oxidative stress in the hippocampus of rats at PND 11 and in the cerebral cortex at PND 90. These findings demonstrate that nociception and oxidative stress was induced in rats dependent on the time of MSG administration, susceptibility of spinal cord and brain regions and the age of rats.

Analgesic and anti-inflammatory activities of methanolic extract of Mallotus repandus stem in animal models

The aim of our current study is to investigate the analgesic and anti-inflammatory potentials of methanolic extract of Mallotus repandus stem (MSM) using different in vivo assay models. Analgesic and anti-inflammatory activities were evaluated using acetic acid induced writhing test, tail immersion method, hot-plate test, formalin induced hind paw licking, xylene induced ear edema, carrageenan-induced paw edema and cotton pellet induced granuloma in animal model at doses of 500, 1000 and 2000 mg/kg body weight. MSM showed significant (p < 0.05) analgesic activities in the acetic acid-induced writhing tests in mice. In the tail immersion and hot-plate test, MSM significantly prolonged the latency period (p < 0.05). Significant (p < 0.05) formalin induced paw licking inhibition was observed at different doses and the highest 74.47% inhibition was observed at 2000 mg/kg. Besides, MSM showed significant (p < 0.05) anti-inflammatory responses in carrageenan induced paw edema, xylene induced ear edema and cotton pellet induced granuloma methods. These findings suggest that the plant may be a potential source for the development of new analgesic and anti-inflammatory agent.

Antinociceptive effectiveness of Tithonia tubaeformis in a vincristine model of chemotherapy-induced painful neuropathy in mice

BackgroundChemotherapy induced peripheral neuropathy (CIPN) is a painful side-effect of commonly used chemotherapeutic agents that profoundly impair the quality of life of patients as the current pharmacotherapeutic strategies are inefficient in providing adequate pain relief. Complementary and alternative medicine (CAM) therapies are preferred by patients with neuropathic pain as they experience insufficient control of pain with conventional medications. This study describes the antinociceptive effect of Tithonia tubaeformis (Jacq.) Cass. in a vincristine mouse model of established CIPN. MethodsTithonia tubaeformis hydromethanolic extract was tested for preliminary qualitative phytochemical analysis and acute oral toxicity test in mice. The antinociceptive effect was investigated using the abdominal constriction (writhing) and tail immersion tests (25–200 mg/kg). The anti-neuropathic effect was determined in the vincristine mouse model, established by daily administration of vincristine (0.1 mg/kg/day, i.p) for consecutive 14 days. Acute treatment with Tithonia tubaeformis (100 and 200 mg/kg) and the positive control, gabapentin (75 mg/kg) was carried out on the 15th day of the last vincrsitine dose and the animals were tested for allodynia and thermal hyperalgesia at 30–120 min post extract/drug administration. ResultsVincristine produced significant temporal tactile allodynia and thermal hyperalgesia (P < 0.01 and P < 0.001 on day 7 and 14) and was maintained for the subsequent day (P < 0.001 during 30–120 min). Tithonia tubaeformis was effective in attenuating the vincristine-induced allodynia and thermal hyperalgesia at 100 mg/kg (P < 0.05, P < 0.01) and 200 mg/kg (P < 0.01, P < 0.001). Similarly, gabapentin also showed a robust antinociceptive effect in counteracting the vincristine associated behavioral alterations. ConclusionsTithonia tubaeformis can be an effective CAM therapeutic remedy for established CIPN due to its potential antinociceptive effect in attenuating vincristine-induced neuropathy.

The Role of TRP and K+ Ion Channels in Analgesic Effect of NSAIDs

Objective: We aimed to clarify the possible contributions of TRP and voltagedependent K+ channels to the analgesic effects of diclofenac, ketoprofen, etodolac, and dipyrone using the nonselective TRP channel blocker ruthenium red and the voltage-dependent K+ channel blocker (Kv7; KCNQ) XE 991, respectively. Methods: We assessed the changes in the antinociceptive effects of diclofenac (50 mg/kg, i.p.), ketoprofen (50 mg/kg, i.p.), etodolac (70 mg/kg, i.p.), and dipyrone (500 mg/kg, i.p.) using ruthenium red (3 mg/kg, i.p.) and XE 991 (1 mg/kg, i.p.) before treatment in the hot plate, tail immersion, and writhing tests in mice. Results: In the tail immersion test, ruthenium red administration resulted in a significant reversal in the analgesic effects of dipyrone, etodolac, and ketoprofen. In the hot plate test, a significant reversal was observed in the analgesic effect of only dipyrone. In the tail immersion test, the administration of XE 991 induced a significant reversal in the analgesic effects of dipyrone and etodolac and a relative reversal in the analgesic effects of ketoprofen and diclofenac. In the hot plate test, XE 991 produced a significant reversal in the analgesic effect of only ketoprofen, whereas it caused a relative reversal in the analgesic effects of other tested nonsteroidal anti-inflammatory drugs (NSAIDs). In the writhing test, no significant change was observed after either XE 991 or ruthenium red administration. Concusions: Modulation of TRP and K+ channels may be involved in the central analgesic effects of NSAIDs. The clarification of different action mechanisms of NSAIDs will contribute to new therapeutic approaches and provide guidance for new drug development studies.

Effect of flavonol and its dimethoxy derivatives on paclitaxel-induced peripheral neuropathy in mice.

AbstractBackground:Peripheral neuropathy is the dose limiting side effect of many anticancer drugs. Flavonoids exhibit good antinociceptive effect in animal models. Their efficacy against different types of nociception has been documented. The present study investigated the effect of flavonol (3-hydroxy flavone), 3′,4′-dimethoxy flavonol, 6,3′-dimethoxy flavonol, 7,2′-dimethoxy flavonol and 7,3′-dimethoxy flavonol against paclitaxel-induced peripheral neuropathy in mice.Methods:A single dose of paclitaxel (10 mg/kg, i.p.) was administered to induce peripheral neuropathy in mice and the manifestations of peripheral neuropathy such as tactile allodynia, cold allodynia and thermal hyperalgesia were assessed 24 h later by employing Von Frey hair aesthesiometer test, acetone bubble test and hot water tail immersion test, respectively. The test compounds were prepared as a suspension in 0.5% carboxymethyl cellulose and were administered s.c. in various doses (25, 50, 100 and 200 mg/kg). The above behavioral responses were assessed prior to and 30 min after drug treatment. In addition, the effect of test compounds on proinflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β) and free radicals was investigated by using suitablein vitroassays.Results:A dose-dependent attenuation of tactile allodynia, cold allodynia and thermal hyperalgesia was evidenced in mice treated with flavonol derivatives. The test compounds inhibited TNF-α, IL-1β and free radicals in a concentration-dependent manner.Conclusions:These results revealed that flavonol and its dimethoxy derivatives ameliorated the manifestations of paclitaxel-induced peripheral neuropathy in mice. The inhibition of proinflammatory cytokines and free radicals could contribute to this beneficial effect.

Effect of certain trimethoxy flavones on paclitaxel - induced peripheral neuropathy in mice

BackgroundThe anti - nociceptive effect of 7, 2′, 3′ – trimethoxy flavone, 7, 2′, 4′ – trimethoxy flavone, 7, 3′, 4′ – trimethoxy flavone and 7, 5, 4′ – trimethoxy flavone against inflammatory, neurogenic and thermal pain in mice was reported earlier. The present study was designed to investigate the effect of the above trimethoxy flavones in amelioration of peripheral neuropathy induced by paclitaxel. MethodsPeripheral neuropathy was induced in mice by administration of a single i.p. dose (10mg/kg) of paclitaxel. The manifestations of peripheral neuropathy such as tactile allodynia, cold allodynia and thermal hyperalgesia were assessed 24h later by employing hair aesthesiometer test, acetone bubble test and hot water tail immersion test respectively. Further, the role of inflammatory cytokines like TNF – α, IL - 1β and free radicals in the action of trimethoxy flavones was investigated using in vitro assays. ResultsThe test compounds dose dependently attenuated paclitaxel - induced tactile allodynia, cold allodynia and thermal hyperalgesia in mice. The test compounds inhibited TNF – α, IL - 1β and free radicals in a concentration dependent manner. ConclusionThe investigated trimethoxy flavones attenuated paclitaxel – induced peripheral neuropathy in mice. The inhibition of cytokines and free radicals in addition to many neuronal mechanisms reported earlier may contribute to this beneficial effect.

Anti-inflammatory and antinociceptive effects of 2,2`-dipyridyl diselenide through reduction of inducible nitric oxide synthase, nuclear factor-kappa B and c-Jun N-terminal kinase phosphorylation levels in the mouse spinal cord

Appropriate treatment of pain requires analgesics and anti-inflammatory drugs generally associated with undesirable side effects and not fully effective in a significant proportion of patients. Organoselenium compounds elicit a plenty of pharmacological effects in different animal models. Among these compounds, the 2,2`-dipyridyl diselenide (DPD) has a potent antioxidant effect and low toxicity. In this way, the aim of this study was to investigate the possible DPD antinociceptive effect and its mechanism of action, as well as the safety of the compound. Female Swiss mice were treated with vehicle or DPD (0.01–50 mg/kg) intragastrically. Dose–response curve and time-course of the antinociceptive effect of DPD were performed on formalin and tail immersion tests. Morphine (2.5 mg/kg, subcutaneous, 15 min earlier) was used as a positive control in behavioral tests. The results showed that DPD presents a rapid antinociceptive effect in low doses, without changing the spontaneous locomotor activity and parameters of toxicity in mice. The DPD antinociceptive effect was also confirmed in male Swiss mice in both formalin and tail immersion tests. In addition, DPD reduced the paw edema induced by 2.5% formalin and ear edema induced by 2.5% croton oil. l-arginine (600 mg/kg, intraperitoneally) reduced the DPD antinociceptive effect in the first phase of the formalin test. Moreover, DPD attenuated the increase in iNOS, NF-κB and JNK phosphorylation in the spinal cord of mice injected with formalin. These results showed that DPD exerts peripheral and central nociceptive actions associated with anti-inflammatory effect and this organoselenium compound could be an interesting alternative therapy for pain treatment.

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.

The possible mechanisms of protocatechuic acid-induced central analgesia

It is aimed to investigate the central antinociceptive effect of protocatechuic acid and the involvement of stimulation of opioidergic, serotonin 5-HT2A/2C, α2-adrenergic and muscarinic receptors in protocatechuic acid-induced central analgesia in mice. Time-dependent antinociceptive effects of protocatechuic acid at the oral doses of 75, 150 and 300 mg/kg were tested in hot-plate (integrated supraspinal response) and tail-immersion (spinal reflex) tests in mice. To investigate the mechanisms of action; the mice administered 300 mg/kg protocatechuic acid (p.o.) were pre-treated with non-specific opioid antagonist naloxone (5 mg/kg, i.p.), serotonin 5-HT2A/2C receptor antagonist ketanserin (1 mg/kg, i.p.), α2-adrenoceptor antagonist yohimbine (1 mg/kg, i.p.) and non-specific muscarinic antagonist atropine (5 mg/kg, i.p.), respectively. The antinociceptive effect of protocatechuic acid was observed at the doses of 75, 150 and 300 mg/kg in tail-immersion test, at the doses of 150 and 300 mg/kg in hot-plate test at different time interval. The enhancement in the latency of protocatechuic acid-induced response to thermal stimuli was antagonized by yohimbine, naloxone and atropine in tail-immersion test, while it was antagonized only by yohimbine and naloxone pretreatments in hot-plate test. These results indicated that protocatechuic acid has the central antinociceptive action that is probably organized by spinal mediated cholinergic and opiodiergic, also spinal and supraspinal mediated noradrenergic modulation. However, further studies are required to understand how protocatechuic acid organizes the interactions of these modulatory systems. As a whole, these findings reinforce that protocatechuic acid is a potential agent that might be used for pain relief. Additionally, the clarification of the effect and mechanisms of action of protocatechuic acid will contribute to new therapeutic approaches and provide guidance for new drug development studies.

Study of analgesic effect of earthworm extract.

Pain represents a major clinical problem and one which has exercised generations of healthcare professionals. Earthworms are used as a traditional Chinese medicine, and have been applied pharmacologically and clinically since a long time in China. However, the analgesic effects of earthworm extract (EE) are seldom studied. Hence, we evaluated the analgesic effects of EE in mice. The obtained data showed that EE increased pain threshold and exhibited peripheral but not central analgesic effects in mice; evidenced by increased inhibition ratio in acetic acid writhing test and formalin test, whereas only slight increase in inhibition ratio in hot plate test and tail immersion test. In addition, EE decreased serum norepinephrine (NE), 5-hydroxytryptamine (5-HT), and nitric oxide (NO) synthase (NOS) concentration, similar to other analgesic drugs like morphine and aspirin. In a nutshell, the obtained data have demonstrated that EE has peripheral analgesic properties and could be used as a promising analgesic drug.

Antinociceptive and Antiinflammatory Activities of Anastatica hierochuntica and Possible Mechanism of Action

Anastatica hierochuntica L. (Brassicaceae) has been used in folk medicine to treat diseases related to inflammation and pain. This study investigated the antinociceptive and antiinflammatory effects of the aqueous extract and the chloroform fraction of A. hierochuntica plant and possible mechanism of action in Swiss albino mice and Wistar rats. The antinociceptive activity was evaluated using the hot-plate, tail immersion, writhing and formalin-induced paw liking tests, while antiinflammatory action was investigated using the carrageenan-induced paw edema in over a period of 5 h in the dose range of 3.16 to 1000 mg/kg, i.p. These effects were compared to those of the vehicle, morphine, indomethacin and the influence of naloxone. Aqueous extract and the chloroform fraction of A. hierochuntica produced significant increase in the pain latency time in the hot-plate and tail-immersion tests (ED50s, 31.0 and 26.3 mg/kg for aqueous extract of A. hierochuntica, 15.0 and 10.1 mg/kg for A. hierochuntica chloroform fraction, respectively). In the acetic acid-induced writhing and formalin test, administration of the aqueous extract and the chloroform fraction of A. hierochuntica significantly reduced the number of writhings (ED50, 28.6 and 8.7 mg/kg, respectively) and time of licking in early (ED50, 18.2 and 10.6 mg/kg, respectively) and late phase (ED50, 18.9 and 11.9 mg/kg, respectively) of formalin-induced pain. Pretreatment of animals with naloxone significantly reversed the antinociceptive effects of the aqueous extract and the chloroform fraction of A. hierochuntica when assessed against hot-plate and formalin test. The aqueous extract and the chloroform fraction of A. hierochuntica significantly inhibited edema formation in carrageenan-induced edema assay (ED50, 29.1 and 6.5 mg/kg, respectively). These results demonstrated that A. hierochuntica has potential central and peripheral antinociceptive effects as well as antiinflammatory activity.

Analgesic and Anti-Inflammatory Activities of Diethyl Ether and n-Hexane Extract of Polyalthia suberosa Leaves.

In folk medicine, Polyalthia suberosa is used as abortifacient, laxative, febrifuge analgesic, filler of tooth cavities, and anti-HIV drug and for rheumatism and various skin infections. The present study was directed to evaluate the analgesic and anti-inflammatory activities of diethyl ether and n-hexane extracts of Polyalthia suberosa leaves (PSDE and PSNH). A variety of tests including formalin-induced paw licking test, acetic acid induced writhing test, and tail immersion test were used to assess the analgesic activity. In addition, xylene-induced ear edema test was used to evaluate anti-inflammatory activity of PSDE and PSNH. PSDE and PSNH at 200 and 400 mg/kg doses expressed analgesic as well as anti-inflammatory activities in mice. In formalin-induced paw licking test, acetic acid induced writhing test, and xylene-induced ear edema test, the extracts exhibited significant inhibition (⁎P < 0.05 versus control) of pain and inflammation. Alternatively, in tail immersion test, PSDE 400 mg/kg showed significant (⁎P < 0.05 versus control) latency at 30 min but another tested sample had no significant latency. From this study, it could be shown that Polyalthia suberosa leaves may contain analgesic and anti-inflammatory agents which support its use in traditional medicine.

Evaluation of the Nutritional Compositions and Analgesic Effects of the Flavonoid Fraction of Eugenia uniflora Ripe Fruit Pulp

Objectives: This present study was carried out to determine the phytochemical compositions, proximate compositions, anti-nutrients content and analgesic activities of the flavonoid fraction from the ripe fruit pulp of Eugenia uniflora. Method: The phytochemical, proximate and anti nutrient compositions of the ripe fruit pulp of Eugenia uniflora and flavonoid extraction were determined using standard methods. The analgesic effect of the flavonoid fraction was evaluated using acetic acid-induced writhing and tail immersion test in mice. A dose 50 mg/ kg body weight of the flavonoid fraction was orally administered using cannula. The activity was compared with a standard reference drug 10 mg/kg diclofenac and normal control. Results: The different phytoconstituents of the fruit pulp include the alkaloids, flavonoids, glycosides, reducing sugar, tannins, terpenoids, saponins and steroids. The proximate showed moisture (90.35%), carbohydrate (4.68%), ash (3.05%), protein (1.31%), fat (0.63%) and fiber (0.11%) contents. The anti-nutrients present included oxalate (34.08%) and cyanogenic glycoside (0.16%). The fraction and the standard drug significantly lowered (p>0.05) the total number of writhes induced by acetic acid. The percentage inhibition decreased from 0% in the normal control to 57.78% at 50 mg/kg of the fraction. The fraction significantly increased (p<0.05) the pain reaction time (PRT) induced by tail immersion test compared to the standard drug and control groups. Conclusion: The fruit has adequate dietary nutrients and the concentration of the anti-nutrients will not be harmful to prevent the consumption of the fruit. It also suggests that E. uniflora fruit pulp possesses effective analgesic activity possibly mediated via both peripheral and central mechanism.

The influence of AMN082, metabotropic glutamate receptor 7 (mGlu7) allosteric agonist on the acute and chronic antinociceptive effects of morphine in the tail-immersion test in mice: Comparison with mGlu5 and mGlu2/3 ligands

Preclinical data indicated that the metabotropic glutamate receptors 5 (mGlu5) and glutamate receptors 2/3 (mGlu2/3) are involved in modulating morphine antinociception. However, little is known about the role of metabotropic glutamate receptors 7 (mGlu7) in this phenomenon. We compared the effects of AMN082 (0.1, 1 or 5mg/kg, ip), a selective mGlu7 allosteric agonist, LY354740 (0.1, 1 or 5mg/kg, ip), an mGlu2/3 agonist and MTEP (0.1, 1 or 5mg/kg, ip), a selective mGlu5 antagonist, on the acute antinociceptive effect of morphine (5mg/kg, sc) and also on the development and expression of tolerance to morphine analgesia in the tail-immersion test in mice. To determine the role of mGlu7 in morphine tolerance, and the association of the mGlu7 effect with the N-methyl-d-aspartate (NMDA) receptors regulation, we used MMPIP (10mg/kg, ip), a selective mGlu7 antagonist and MK-801, a NMDA antagonist. Herein, the acute administration of AMN082, MTEP or LY354740 alone failed to evoked antinociception, and did not affect morphine (5mg/kg, sc) antinociception. However, these ligands inhibited the development of morphine tolerance, and we indicated that MMPIP reversed the inhibitory effect of AMN082. When given together, the non-effective doses of AMN082 and MK-801 did not alter the tolerance to morphine. Thus, mGlu7, similarly to mGlu2/3 and mGlu5, are involved in the development of tolerance to the antinociceptive effects of morphine, but not in the acute morphine antinociception. Furthermore, while mGlu7 are engaged in the development of morphine tolerance, no interaction exists between mGlu7 and NMDA receptors in this phenomenon.

In vivo analgesic and anti-inflammatory properties of the aqueous extract of Pistacia atlantica Desf. from Morocco

The present study analyses the pharmacological activity in vivo models of the aqueous extract obtained from Pistacia atlantica Desf of Morocco. The plant selected for this study have been used in traditional medicine in Morocco for the treatment of various diseases that are considered as inflammation in nature, e.g. arthritis, rheumatism, fever, and related inflammatory diseases. The result of this study showed that the aqueous extract of Pistacia atlantica Desf. lacked toxicity, but exhibited a high analgesic effect in writhing Test and in tail immersion Test suggesting the induction of a peripheral and central analgesic response. The aqueousextract of this plant also exhibited an anti-inflammatory action inhibiting the rat paw edema induced by carrageenin and experimental trauma. We can conclude that the aqueousextractof Pistacia atlantica Desf. Possesses potential anti-inflammatory activities, supporting the traditional application of this plant in treating various diseases associated with inflammation and pain in Morocco.

Ghrelin attenuated hyperalgesia induced by chronic nitroglycerin: CGRP and TRPV1 as targets for migraine management.

Background According to the neurovascular theory of migraine, activation of the trigeminovascular system contributes to the development of migraine. This study examined the effects of chronic intraperitoneal ghrelin (150 µg/kg) treatment on the development of chronic migraine induced by intermittent injection of nitroglycerin 10 mg/kg. Methods Baseline and post-drug (2 h following nitroglycerin injection) mechanical and thermal sensitivity were assessed by von Frey hair and tail immersion tests, respectively on days 1, 3, 5, 7, 9 and 11. Moreover, we investigated the effect of ghrelin treatment on nitroglycerin-induced aversive behavior by using a two-chamber conditioned place aversion paradigm. At the end of behavioral testing, on day 11, animals were sacrificed and plasma concentration of calcitonin gene-related peptide was measured using a rat-specific enzyme-linked immunosorbent assay kit. Also, real time polymerase chain reaction was used to quantify mRNA expression of calcitonin gene-related peptide and transient receptor potential vanilloid 1 in the trigeminal ganglion. Results Our results indicated that nitroglycerin activated the trigeminovascular system, which was reflected by mechanical and thermal hypersensitivity and elevation of mRNA expression of calcitonin gene-related peptide and transient receptor potential vanilloid-1, as migraine markers, and plasma calcitonin gene-related peptide levels. Moreover, chronic nitroglycerin injection induced conditioned place aversion and body weight loss. Nevertheless, ghrelin modulated nitroglycerin-triggered changes in transient receptor potential vanilloid-1 and calcitonin gene-related peptide expression, and mitigated nitroglycerin-induced hyperalgesia. Conclusion These results provide the first convincing evidence that ghrelin has a modulating effect on central sensitization induced by chronic intermittent nitroglycerin, and its antinociceptive effect may be related to a reduction of these factors in the trigeminal ganglion.

Assessment on antinociceptive actions of soluble fractions derived from edible mollusc (Bellamya bengalensis Lam.)

Background: Bellamya bengalensis, an edible bivalve mollusc is traditionally used in the treatment of joint pain, bone fracture, jaundice and eye infections. Present study was designed to find out the most potent analgesic fractions derived from the body mass of Bellamya bengalensis.Methods: The test specimen was collected, identified and fractionated with solvent medium like, phosphate buffer saline (PB), ethyl acetate (EB), methanol (MB) and chloroform (CB). Protein concentration of each fraction was determined. The antinociceptive activities were measured either by thermal models like, hot plate and tail immersion (central analgesic action) or by chemical model like acetic acid induced writhing (peripheral analgesic action) in mice. Diclofenac sodium was used as analgesic standard.Results: Significant peripheral and central analgesic activity showed by phosphate buffer saline fraction at 100mg/kg, even better than diclofenac standard at 10mg/kg. In hot plate and tail immersion tests, phosphate buffer saline showed the highest activity followed by methanol, chloroform and ethyl acetate fraction respectively. However, in case of peripheral analgesic experiment, phosphate buffer fraction exhibited maximum writhing inhibitory properties and that was followed by chloroform, methanol and ethyl acetate fraction respectively.Conclusions: Phosphate buffer saline fraction of Bellamya bengalensis showed maximum potential central and peripheral analgesic activity than any other fractions.