Tail Immersion Test Research Articles

Evaluation of the effects of novel nafimidone derivatives on thermal hypoalgesia in mice with diabetic neuropathy.

Diabetic neuropathy (DN) is a common complication in Diabetes Mellitus. The streptozotocin-induced diabetic rodent is the most commonly used animal model of diabetes and increased sodium channel expression and activity were revealed in this model. At this study, we evaluated the effect of three different nafimidone derivatives which have possible anticonvulsant activity on disorders of thermal pain sensation in diabetic mice. Randomized animal experiment. Mice were divided randomly into five groups (5 mice per group): Control, Diabetes, Dibetes+C1, Diabetes+C2, Diabetes+C3. We used hot and cold plate, and tail-immersion tests for assessment of thermal nociceptive responses. Compared with the control group, the hot-plate response time and the number of paw liftings on cold plate as important indicators of loss of sensation increased, but no significant difference (p>0.05) was found in tail-immersion response time test in diabetes group. C3 compound moved it back to control group levels in the all of three tests. C1 and C2 compounds were effective only in cold-plate test. Nafimidone derivatives may be effective in the cases where epilepsy and diabetes occur together since it has shown efficacy against "loss of sensation" which evolves in diabetic neuropathy over time as well as its antiepileptic effect.

A comparison of the antinociceptive and temperature responses to morphine and fentanyl derivatives in rats

In addition to producing antinociception, opioids exert profound effects on body temperature. This study aimed at comparing antinociceptive and hyperthermic responses between two groups of μ-opioid receptor agonists: fentanyl (4-anilinopiperidine-type) and morphine (phenanthrene-type) derivatives in rats. Analgesic activity was assessed by tail immersion test and the body temperature by insertion of a thermometer probe into the colon. Fentanyl (F), (±)-cis-3-methyl fentanyl (CM), (±)-cis-3-carbomethoxy fentanyl (C), (±)trans-3-carbomethoxy fentanyl (T) and (±)-cis-3 butyl fentanyl (B) produced dose-dependent increase in antinociception and hyperthermia. The relative order of analgesic potency was: CM(11.27)>F(1)>C(0.35)≥T(0.11)≥B(0.056). Similar to this, the relative order of hyperthermic potency was: CM(8.43)>F(1)>C(0.46)≥T(0.11)≥B(0.076). Morphine (M), oxycodone (O), thebacon (T) and 6,14-ethenomorphinan-7-methanol, 4,5-epoxy-6-fluoro-3-hydroxy-α,α,17-trimethyl-, (5α,7α) (E) also produced dose-dependent increase in antinociception and hyperthermia. Among morphine derivatives the relative order of analgesic potency was: E(56)>O(5)≥T(2.6)>M(1), and similar to this, the relative order of hyperthermic potency was: E(37)>O(3)≥T(2.3)>M(1). Morphine (phenanthrene-type) and fentanyl (4-anilinopiperidine-type) derivatives produced hyperthermia in rats at doses about 2 times lower, and 6-11 times higher, than their median antinociceptive doses, respectively. This study is first to identify difference between these two classes of opioid drugs in their potencies in producing hyperthermia. Further studies are needed to clarify the significance of these findings.

Analgesic and Anti-inflammatory Profile of n-Hexane Fraction of <i>Viola betonicifolia</i>

Purpose: To evaluate the analgesic and anti-inflammatory activities of n-hexane extract of the whole plant of Viola betonicifolia Sm, family: Violaceace.Methods: The n-hexane fraction of Viola betonicifolia (VBHF) was tested for its analgesic and antiinflammatory activities (carrageenan-induced and histamine-induced edema models) in BALB/c mice.Results: VBHF exhibited significant (p < 0.01) analgesic and anti-inflammatory activity at test doses of 100, 200 and 300 mg/kg. The analgesic effect of VBHF was dose-dependent in acetic acid pain modelwhile the extract was a weak analgesic at the dose of 300 mg/kg in hot plate and tail immersion test. Diclofenac sodium and tramadol showed better analgesic properties to the extract. Analgesia was not antagonized by naloxone in the hot plate model. Anti-inflammatory activity against carrageenan-induced edema was 60.8 %; however, histamine-induced inflammation was not antogonised by the extract.Conclusions: The extract has some analgesic and anti-inflammatory activities. This justifies its use in traditional medicine for pain of management.Keywords: Viola betonicifolia, Analgesic, Anti-inflammatory.

Dietary component p-coumaric acid suppresses monosodium urate crystal-induced inflammation in rats

This study was conducted to evaluate the effect of p-Coumaric acid, a common dietary phenol, on monosodium urate crystal-induced inflammation in rats-an experimental model for acute gouty arthritis. Paw edema, levels/activities of lysosomal enzymes, lipid peroxidation, enzymic antioxidants and a histopathological examination of ankle joints were evaluated in control and monosodium urate crystal-induced inflamed rats. Further, an acetic acid-induced writhing test and tail immersion test were employed to screen for analgesic effects, yeast-induced pyrexia was used to test for antipyretic effects, and gastric ulceration was used to evaluate ulcerogenic effects. A significant increase in paw edema, lysosomal enzyme activity and lipid peroxidation levels was observed in monosodium urate crystal-induced rats, whereas activities of enzymic antioxidants were found to be decreased when compared to control rats. Nevertheless, treatment with p-Coumaric acid (100mg/kgb.wt) significantly reverted the altered physical and biochemical parameters back to near normal levels, as evidenced by the histopathology of the ankle joints. In addition, p-Coumaric acid also exhibited potent analgesic and antipyretic effects devoid of any adverse impact on gastric mucosa. The results of this study reveal the potential anti-inflammatory effect of p-Coumaric acid against monosodium urate crystal-induced inflammation in rats.

Analgesic and anti-inflammatory activity of the aqueous leaf extract of <i>Piliostigma thonningii</i> (Caesalpinoideae)

The leaves of Piliostigma thonningii (Schum) have been used in herbal medicine to arrest bleeding, as laxatives, to treat fevers, bacterial infection and inflammation. In order to provide scientific justification for the ethnomedical uses of the leaves, the study was designed to investigate the analgesic and anti-inflammatory activity of the extract and its possible mechanism of action. Analgesic activity was examined using the tail immersion and acetic acidinduced writhing test while acute anti-inflammatory effect was studied using xylene-induced ear edema model. The extract significantly (p<0.05) decreased the number of writhes in the mice at 200 and 400 mg/kg doses of the extract with 54.95 and 56.53% inhibition respectively but did not show any significant effect (p>0.05) in the tail immersion test when compared to the control. There was a significant decrease (p<0.001) in ear oedema induced by xylene by 200 and 400 mg/kg of the extract with 83.06 and 90.55% inhibition respectively. Oral acute toxicity assays did not show any mortality at 10 g/kg of the plant extract. The inhibition of acetic acid-induced writhing inmice by extract suggested that its analgesic affect maybe be peripherally mediated and the inhibition of edema suggests a likely indication of the antiphlogistic effects of the extract. In conclusion, the leaf extract of P. thonningii possesses anti-inflammatory and analgesic properties which may be mediated via peripheral inhibiting mechanisms. These results thus justify its use in the treatment of pain and inflammatory conditions in tradomedical practice.Keywords: Piliostigma thonningii; anti-inflammatory; analgesic

Phytochemical Screening and Anti-nociceptive Properties of the Ethanolic Leaf Extract of Trema Cannabina Lour.

The present study was designed to investigate the anti-nociceptive activity of ethanolic leaf extract of Trema cannabina Lour (family: Cannabaceae) in experimental animal models. The anti-nociceptive action was carried out against two types of noxious stimuli, thermal (hot plate and tail immersion tests) and chemical (acetic acid-induced writhing) in mice. Phytochemical analysis of crude extract indicated the presence of reducing sugar, tannins, steroid and alkaloid types of secondary metabolites. Crude extract of T. cannabina (500 mg/kg dose) showed maximum time needed for the response against thermal stimuli (6.79±0.15 seconds) which is comparable to diclofenac sodium (8.26±0.14 seconds) in the hot plate test. Hot tail immersion test also showed similar results as in hot plate test. At the dose of 250 and 500 mg/kg body weight, the extract showed significantly and in a dose-dependent (p<0.001) reduction in acetic acid induced writhing in mice with a maximum effect of 47.56% reduction at 500 mg/kg dose comparable to that of diclofenac sodium (67.07%) at 25 mg/kg. The obtained results tend to suggest the Anti-nociceptive activity of ethanolic leaf extract of Trema cannabina and thus provide the scientific basis for the traditional uses of this plant part as a remedy for pain.

Bis(phenylimidazoselenazolyl) diselenide

The present study examined the effect of peroral administration of bis(phenylimidazoselenazolyl) diselenide (BPIS) in thermal and chemical models of pain in mice. The involvement of the opioid system in the BPIS antinociceptive effect was also examined, as well as potential nonspecific disturbances in locomotor activity or signs of acute toxicity. BPIS (25-100 mg/kg) induced an increase in tail-immersion response latency and this effect was significant at pretreatment times of 15 min to 4 h, but not at 8 h. The hot-plate response latency was also increased by the administration of BPIS (25-100 mg/kg). BPIS, at doses of 25 and 50 mg/kg, inhibited writhing behaviour caused by an intraperitoneal acetic acid injection. Both early and late phases of nociception caused by the intraperitoneal formalin injection were inhibited by BPIS (10-50 mg/kg). BPIS, administered at doses equal to or greater than 10 and 25 mg/kg, reduced nociception produced by an intraperitoneal injection of capsaicin and glutamate, respectively. The antinociceptive effect of BPIS, when assessed in the tail-immersion test, was not abolished by naloxone. BPIS (10-50 mg/kg) did not alter alanine transaminase and aspartate transaminase activities (parameters of hepatic function) or urea and creatinine levels (parameters of renal function), and did not affect motor activity in the open-field test. The results indicate that BPIS produced an antinociceptive action without causing motor disturbances or toxicity. Moreover, opioidergic mechanisms seem not to be involved in the antinociceptive action of BPIS. Here, BPIS has been found to be a novel organoselenium compound with antinociceptive properties; however, more studies are required to examine its therapeutic potential for pain treatment.

Prasarani Sandhan, a Polyherbal Preparation, Shows Anti-nociceptive and Anti-inflammatory Activities

Aims: Prasarani Sandhan (PRS) is an Ayurvedic formulation approved by the “National formulary of Ayurvedic Medicine 2011”, of Bangladesh. It is traditionally used in arthritic pain, lumbago and sciatia. Sparse scientific evidence is available to support the efficacy of this preparation. Hence, we planned to document scientific evidences of the pharmacological activity of this preparation. Study Design: Our present study aims to elucidate the probable anti-nociceptive and anti-inflammatory mechanisms of PRS. Place and Duration of the study: The experiments were performed at the pharmacology lab of North South University during the period of October 2010 to July 2011. Methodology: Two thermal anti-nociceptive models were used, the hot-plate test and tail immersion test, to find out the possible role of the central nervous system in its action. Three in-vivo analgesic and anti-inflammatory models, carrageenan induced paw edema, acetic-acid writhing, and formalin induced paw lick tests, were carried out to test its potential anti-inflammatory and peripheral analgesic properties. Result: The study of PRS (20mL/kg and 40mL/kg) showed no involvement of the CNS in anti-nociceptive activity of PRS. Carrageenan induced paw edema and acetic acid writhing tests both gave significant results (P=.05), indicating possible peripheral analgesic and anti-inflammatory action. Formalin induced paw-licking test (with and without naloxone co-administration), a differentiator of nurogenic pain (CNS modulated) and inflammatory pain (peripheral nociception), showed that PRS had significant effect in suppressing inflammatory pain (P=.05) but not neurogenic pain. Conclusion: Compiling the results of the experiments, it can be reported that PRS has anti-inflammatory and peripheral analgesic action.

Investigation on Central and Peripheral Analgesic and Anti-Inflammatory Activity of Punarnavasava, an Ayurvedic Preparation

Aims :Punarnavasava (PNR) is an Ayurvedic formulation approved by theNational formulary of Ayurvedic Medicine 2011 �, of Bangladesh. It is traditionally used in arthritic pain, lumbago and sciatia. Sparse sci entific evidence is available to support the efficacy of this preparation. Hence, we planned to document scientific evidences of the pharmacological activity of this preparation. Study Design: Our present study aims to elucidate the probable anti -nociceptive and anti-inflammatory mechanisms of PNR. Place and Duration of theStudy:The experiments were performed at the pharmacology lab of North South University during the period of October 2010 to July 2011. Methodology: Two thermal anti-nociceptive models were used, the hot-plate test and tail immersion test, to find out the possible role of the central nervous system in its action. Three in-vivo analgesic and anti -inflammatory models, carrageenan induced paw edema, acetic-acid writhing, and formalin indupaw lick tests, were carried out to test its potential anti -inflammatory and peripheral analgesic properties. Results:The dose dependent study of PNR (10mL/kg, 20mL/kg, and 40mL/kg) showed potential involvement of the CNS in anti -nociceptive activityof PNR. Carrageenan induced paw edema and acetic acid writhing tests both gave significant results (P=.05), indicating possible peripheral analgesic and anti -inflammatory action. Formalin induced

Prasarani Sandhan, a Polyherbal Preparation, Shows Anti-nociceptive and Anti-inflammatory Activities

Aims: Prasarani Sandhan (PRS) is an Ayurvedic formulation approved by the “National formulary of Ayurvedic Medicine 2011”, of Bangladesh. It is traditionally used in arthritic pain, lumbago and sciatia. Sparse scientific evidence is available to support the efficacy of this preparation. Hence, we planned to document scientific evidences of the pharmacological activity of this preparation. Study Design: Our present study aims to elucidate the probable anti-nociceptive and anti-inflammatory mechanisms of PRS. Place and Duration of the study: The experiments were performed at the pharmacology lab of North South University during the period of October 2010 to July 2011. Methodology: Two thermal anti-nociceptive models were used, the hot-plate test and tail immersion test, to find out the possible role of the central nervous system in its action. Three in-vivo analgesic and anti-inflammatory models, carrageenan induced paw edema, acetic-acid writhing, and formalin induced paw lick tests, were carried out to test its potential anti-inflammatory and peripheral analgesic properties. Result: The study of PRS (20mL/kg and 40mL/kg) showed no involvement of the CNS in anti-nociceptive activity of PRS. Carrageenan induced paw edema and acetic acid writhing tests both gave significant results (P=.05), indicating possible peripheral analgesic and anti-inflammatory action. Formalin induced paw-licking test (with and without naloxone co-administration), a differentiator of nurogenic pain (CNS modulated) Research Article British Journal of Pharmaceutical Research, 3(2): 232-246, 2013 233 and inflammatory pain (peripheral nociception), showed that PRS had significant effect in suppressing inflammatory pain (P=.05) but not neurogenic pain. Conclusion: Compiling the results of the experiments, it can be reported that PRS has anti-inflammatory and peripheral analgesic action.

The Antioxidant Effects of the Flavonoids Rutin and Quercetin Inhibit Oxaliplatin-Induced Chronic Painful Peripheral Neuropathy

BackgroundOxaliplatin, the third-generation platinum compound, has evolved as one of the most important therapeutic agents in colorectal cancer chemotherapy. The main limiting factor in oxaliplatin treatment is painful neuropathy that is difficult to treat. This side effect has been studied for several years, but its full mechanism is still inconclusive, and effective treatment does not exist. Data suggest that oxaliplatin’s initial neurotoxic effect is peripheral and oxidative stress-dependent. A spinal target is also suggested in its mechanism of action. The flavonoids rutin and quercetin have been described as cell-protecting agents because of their antioxidant, antinociceptive, and anti-inflammatory actions. We proposed a preventive effect of these agents on oxaliplatin-induced painful peripheral neuropathy based on their antioxidant properties.MethodsOxaliplatin (1 mg/kg, i.v.) was injected in male Swiss mice, twice a week (total of nine injections). The development of sensory alterations, such as thermal and mechanical allodynia, was evaluated using the tail immersion test in cold water (10°C) and the von Frey test. Rutin and quercetin (25-100 mg/kg, i.p.) were injected 30 min before each oxaliplatin injection. The animals’ spinal cords were removed for histopathological and immunohistochemical evaluation and malondialdehyde assay.ResultsOxaliplatin significantly increased thermal and mechanical nociceptive response, effects prevented by quercetin and rutin at all doses. Fos immunostaining in the dorsal horn of the spinal cord confirmed these results. The oxidative stress assays mainly showed that oxaliplatin induced peroxidation in the spinal cord and that rutin and quercetin decreased this effect. The flavonoids also decreased inducible nitric oxide synthase and nitrotyrosine immunostaining in the dorsal horn of the spinal cord. These results suggest that nitric oxide and peroxynitrite are also involved in the neurotoxic effect of oxaliplatin and that rutin and quercetin can inhibit their effect in the spinal cord. We also observed the preservation of dorsal horn structure using histopathological analyses.ConclusionsOxaliplatin induced painful peripheral neuropathy in mice, an effect that was prevented by rutin and quercetin. The mechanism of action of oxaliplatin appears to be, at least, partially oxidative stress-induced damage in dorsal horn neurons, with the involvement of lipid peroxidation and protein nitrosylation.

758 – 3-alkyl fentanyl analogues: structure-activity-relationship study

Fentanyl, the prototype of the 4-anilidopiperidine class of a synthetic opioid analgesics, is widely used to supplement general anesthesia or to treat postoperative and cancer pain. In order to discover an analgesic with the improved pharmacodynamic and pharmacokinetic profile, extensive efforts during last five decades have been devoted to synthesis of a large number of fentanyl analogues and establishing the structure-activity-relationship (SAR) of the 4-anilido-piperidine class of analgesics. This study is aimed to examine the analgesic activity of some newly synthesized 3-alkyl fentanyl analogues and compared with fentanyl. Antinociception is measured by using tail-immersion test in male Wistar rats.The relative potency was: (±)cis-3-methyl fentanyl (8)>(±)trans-3-methyl fentanyl (2)≥(±)cis-3-ethyl fentanyl (1.5)>fentanyl (1)≥(±)trans-3-ethyl fentanyl (0.9)>(±)cis-3- butyl fentanyl (0.064)≥(±)trans-3-butyl fentanyl (0.035)>(±)cis-3-benzyl fentanyl (0.008)≥(±)trans-3-benzyl fentanyl (0.0055). The duration of action (ED 99 ) was: (±)cis-3-methyl fentanyl (90min)>(±)trans-3-methyl fentanyl (40min)≤(±)cis-3-ethyl fentanyl (60min)≥(±)trans-3-ethyl fentanyl (40min)≤fentanyl (50min)=(±)cis-3-butyl fentanyl (50min)=(±)trans-3-butyl fentanyl (50min)=(±)cis-3-benzyl fentanyl (50min)=(±)trans-3-benzyl fentanyl (50min). Pharmacological results show that groups in position 3 of the piperidine ring, which are larger than methyl, severely reduce the analgesic potency compared to fentanyl. It is likely that the steric factor (i.e. voluminosity of the group and cis/trans isomerism) plays a crucial role in the analgesic potency of this series. Although the duration of action, in general, does not depend on the stereochemistry, longer action of the most potent 3-alkyl fentanyl analogues such as cis-3-methyl- and cis-3-ethyl fentanyl, is more likely influenced by pharmacodynamic, rather than pharmacokinetic variables.

Antimicrobial, anti-inflammatory, and antinociceptive activities of triazole, pyrazole, oxadiazine, oxadiazole, and sugar hydrazone-5-nitroindoline-2-one derivatives and a study of their computational chemistry ( part II)

Objective The aim of this study (part II) is to evaluate the antibacterial, anti-inflammatory, and antinociceptive activities of a series of 1H-1,2,4-triazol-3-yl)phenylimino)(methylbenzyl)-5-nitroindolin-2-ones, 1H-pyrazole-1-carbonyl)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-ones, 3-(4-(1,3,4-oxadizine-6-one)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-ones, 1,3,4-oxadiazol-2-yl)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-ones and 4-(-1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino) sugar hydrazone derivatives (1–13) and, in addition, to investigate their computational chemistry. Methods The synthesized compounds in (part I) 1–9 were evaluated for their antibacterial and antifungal activities using different strains of Gram-positive bacteria (Bacillus subtilis), Gram-negative bacteria (Pseudomonas aeruginosa), yeast (Candida albicans), and four mold fungi (Fusarium solani, Aspergillus niger, Colletotrichum gloeosporioides, and Phomopsis obscurans). The anti-inflammatory and antinociceptive activities of compounds 1–13 were evaluated using a hot-plate test, acetic acid-induced writhing in mice, formalin-induced nociception, a tail immersion test, and carrageenan-induced hind paw edema. For computational chemistry, a semiempirical MNDO method (Modified Neglect of Differential Overlap is a semi-empirical method for the quantum calculation of molecular electronic structure in computational chemistry) associated with HyperChem professional 7.5 programs was adapted. Results and conclusion Compounds 4-[(1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino)] benzohydrazide (3) and 3-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-one (9) showed the highest antibacterial and antifungal activities compared with clotrimazole and sulfamethoxazole as reference drugs. In contrast, compounds ethyl 4-(5-nitro-2-oxoindolin-3-ylideneamino) benzoate (1), 3-(4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazole-1-carbonyl) phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-one (8), D-glucose-4-(-1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino) hydrazone derivative (10), and D-arabinose-4-(-1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino) hydrazone derivative (12) showed significantly high anti-inflammatory and antinociceptive activities when compared with indomethacin and morphine as reference drugs. From the computational chemistry compounds, ethyl 4-(5-nitro-2-oxoindolin-3-ylideneamino) benzoate (1), ethyl 4-[(1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino)] benzoate (2), and 4-[(1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino)] benzohydrazide (3) yielded the lowest values of total energy and heat of formation, and had higher stability than other molecules.

Potential role of Tamoxifen as a secondary analgesic for chemotherapy induced neuropathic pain

Pharmacological modulation of TRPV1 receptor is a promising way of producing analgesia in neuropathic pain models. in the present study we investigated the effect of Tamoxifen, PCK inhibitor ,on thermal hyperalgesia in rats after sciatic nerve injury induced by vincristine. Vincristine administration decreased the withdrawal latencies assessed by tail immersion and hot plate tests ,also it increased the level of inflammatory mediators , spinal NO and serum TNFα levels. Tamoxifen ,administered orally every 2 days one hour before vincristine injection till 7 times, resulted in the increase in withdrawal latencies compared to that of vincristine, also showed a decrease in spinal NO and serum TNFα levels. these findings suggested that TRPV1 receptor has a potential role in vincristine induced painful neuropathy and open the door for tamoxifen to be used as secondary analgesic in painful neuropathies.

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.

English

The berry of&nbsp;Solanum aculeastrum&nbsp;is used among other remedies, for treating inflammatory-related ailments in South Africa. The aqueous extract of the fresh berries at 25, 50 and 75 mg/kg body weight was evaluated for anti-inflammatory and analgesic effects in rats using histamine and carrageenan-induced paw oedema, as well as formalin and tail immersion tests. The result of the phytochemical screening indicated that the berries possess alkaloids, saponins, phenolics, flavonoids, cardenolides and dienolides. Oral administration of the extract significantly reduced the formation of oedema induced by carrageenan and histamine after 3 h. The extracts also prolonged the reaction time in the tail immersion-induced pain 60 min after administration. In addition, the extract significantly suppressed the nociceptive response in the early and late phases of the formalin-induced pain in a dose-dependent manner, with more pronounced effect on the late phase. These results also compared well with those of indomethacin, the reference drug used in this study. This study therefore gives credence to the traditional uses of&nbsp;S. aculeastrum&nbsp;in the treatment of certain conditions associated with inflammatory pain. &nbsp; Key words:&nbsp;Solanum aculeastrum,&nbsp;anti-inflammatory, analgesic

Neonatal DSP-4 Treatment Modifies Antinociceptive Effects of the CB1-Receptor Agonist Methanandamide in Adult Rats

To study the influence of the central noradrenergic system on antinociceptive effects mediated by the CB1-receptor agonist methanandamide, intact rats were contrasted with rats in which noradrenergic nerves were largely destroyed shortly after birth with the neurotoxin DSP-4 [N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (50 mg/kg sc × 2, P1 and P3); zimelidine (10 mg/kg sc, 30 min pretreatment, selective serotonin reuptake inhibitor). When rats attained 10 weeks of age, monoamine and their metabolite concentrations were determined in the frontal cortex, thalamus, and spinal cord by an HPLC/ED method. Antinociceptive effects after methanandamide (10 mg/kg ip) apply were evaluated by a battery of tests. In addition, immunohistochemistry and densitometric analysis of the cannabinoid CB1 receptor in the rat brain was performed. DSP-4 lesioning was associated with a reduction in norepinephrine content of the frontal cortex (>90 %) and spinal cord (>80 %) with no changes in the thalamus. Neonatal DSP-4 treatment produced a significant reduction in the antinociceptive effect of methanandamide in the tail-immersion test, hot-plate test and writhing tests. In the paw pressure and formalin hind paw tests results were ambiguous. These findings indicate that the noradrenergic system exerts a prominent influence on analgesia acting via the cannabinoid system in brain, without directly altering CB1 receptor density in the brain.

Ameliorative effect of Vernonia cinerea in vincristine-induced painful neuropathy in rats

The present study was designed to investigate the antinociceptive potential of Vernonia cinerea (VC) on vincristine-induced painful neuropathy in rats. A chemotherapeutic agent, vincristine (50 μg/kg intraperitoneally for 10 consecutive days), was administered for the induction of neuropathic pain in rats. The painful behavioral changes were assessed using hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests to assess the degree of hyperalgesic and allodynic pain sensation in paw and tail. Tissue biomarker changes including thiobarbituric acid reactive substances (TBARSs), reduced glutathione (GSH) and total calcium levels were estimated in sciatic nerve tissue samples to assess the degree of oxidative stress. Histopathological changes were also observed in transverse sections of rat sciatic nerve tissue. Ethanolic extract of VC leaves and pregabalin were administered for 14 consecutive days from day 0 (day of surgery). Pregabalin served as a positive control in the present study. Vincristine administration resulted in a significant reduction in painful behavioral changes along with a rise in the levels of TBARS, total calcium and decrease in GSH levels when compared with the normal control group. Furthermore, significant histopathological changes were also observed. Pretreatment with VC significantly attenuated vincristine-induced development of painful behavioral, biochemical and histological changes in a dose-dependent manner, which is similar to that of pregabalin-pretreated group. The attenuating effect of VC in vincristine-induced nociceptive painful sensation may be due to its potential of antioxidative, neuroprotective and calcium channel inhibitory action.

Evaluation of the In Vivo Anti‐Inflammatory and Analgesic Activity of a Highly Water‐Soluble Aspirin Conjugate

Glucose-aspirin (GA) was synthesized by conjugating aspirin (ASA) to the 3-carbon of glucose to produce a stable water-soluble aspirin derivative. The in vivo activities were compared with those of aspirin. The mouse tail flick assay showed that at 120 min., both aspirin and GA showed the maximum possible effect, and the higher dose (200 mg/kg) generally had less of an effect than the lower dose (100 mg/kg). Per cent inhibition of paw oedema was 63% and 69% for ASA and GA at 100 mg/kg, respectively. In the tail immersion test, the increase in reaction time was significantly greater with GA as compared to aspirin (100 mg/kg) at 60 min. In conclusion, there was significant anti-inflammatory and analgesic activity for GA at the doses studied under the experimental conditions.