一种红蜂胶提取物治银屑病、消炎及镇痛作用(英文)

AIM: To study the antipsoriatic, anti-inflammatory, and analgesic effects of ethanolic extract of red propolis. METHODS and RESULTS: This extract induced the formation of granular layer in the mouse tail test used as a model of psoriasis. Propolis 50 mg·kg-1 ig showed anti-inflammatory activity in the cotton-pellet granuloma assay in rats, in croton oil-induced edema in mice at a dose of 25 % (2.5μL), and in the peritoneal capillary permeability test in mice at a dose of 10 mg·kg-1. The extract (25 mg·kg-1 ig) showed analgesic effect in the model of acetic acid-induced writhings, whereas 40 mg·kg-1 was effective in the hot plate test in mice. CONCLUSION- Anti-inflammatory, analgesic, and antipsoriatic properties of Cuban red propolis were evident.     

Studies on the antinociception effect of melatonin and its mechanism in the rat

The antinociception effect of melatonin（Mel） and its mechanisms were studied on the trauma- pain model in the rat. A trauma - pain model was established in Wistar rats by combining right - hind limb amputation with 50℃ tail - flick test. The effects of Mel on central sensitization were studied through measuring the changes of the expression of c - fos （ an indicator of nociceptive transmission at the spinal level ） , subtance P（SP） and brain - derived neurotrophic factor （BDNF） in the spinal cord using immunohistochemistry. In addition, the contents of nitric oxide （NO） in brain and spinal tissues were also observed. The results showed that the immunoreactivity of BDNF and c - fos in spinal dorsal horn in injuried rats began to increase at the first day,     

The active alkaloids of Gelsemium elegans Benth are potent anxiolytics

OBJECTIVE To investigated whether acute subcutaneous administration of G.elegans alkaloids(eg,gelsemine,koumine,gelsevirine,gelsenicine) were capable of exerting anxiolytic and antidepressant effects in mouse models of these disorders.METHODS We used two mouse models of anxiety(elevated plus-maze and light-dark transition model),and two mouse models of depression(forced swim test and tail suspension test) to examine whether the G.elegans alkaloids are capable of attenuating anxiety-and depressive-like behaviors.RESULTS Gelsemine,koumine and gelsevirine exhibited potent anxiolytic effects in both the elevated plus-maze and the light-dark transition model.Gelsenicine,on the other hand,had no effect on the behavioural response in either of the anxiety models.None of the G.elegans alkaloids exerted antidepressant effects in the forced swim test and the tail suspension test.Importantly,none of the G.elegans alkaloids impaired spontaneous motor activities.CONCLUSION Gelsemine,koumine and gelsevirine might serve as potential candidates for the treatment of anxiety-related disorders in clinical trials with human patients.     

Antinociception of ciproxifan in mice and its central mechanisms

AIM To investigate the effects of ciproxifan (CPF), an H3 receptor antagnist, on modulation of pain transmission in mice and its central mechanism. METHODS The antinociceptive effect of CPF was observed in three hyperalgesic models of mice (hot plate test, writhing test and formalin test). At the same time, α-fluoromethylhistidine (α-FMH), a specific inhibitor of histidine decarboxylase(HDC), was used to determine whether histamine participate in this process. After formalin test, the levels of nitric oxide (NO) and prostaglandin E2 (PGE2) in brain, spinal and serum were assessed. Furthermore, the activation of neuronal nitric oxide synthase (nNOS) in brain and spinal cord was observed by immunohistology and Western blot in formalin test. RESULTS CPF produced antinociceptive effect inall of the three hyperalgesic models.     

Widespread enhancement of pain sensitivity in MRL/MpJ mice following infraorbital nerve transection

OBJECTIVE Neuropathic pain in humans may spread to regions beyond the area innervated by the injured nerve.This study aims to verify the appearance of wide-spread neuropathic pain following infraorbital nerve transection and investigate the mechanisms underlying wide-spread pain.METHODS The infraorbital nerve of male MRL/MPJ mice was transected(ION-T) to induce trigeminal neuralgia under isoflurane anesthesia.The sensitivities to tactile and heat stimuli of different body parts including the vibrissal pads,hindpaws,and tail were tested after surgery.Activation of microglia in the dorsal horn at levels of medulla(MDH) and L4/L5(SDH) were measured by immunohistochemistry.RESULTS Compared to sham-operated mice,injured mice showed significantly mechanical allodynia,heat allodynia and hyperalgesia in the ipsilateral vibrissal pad,and extraterritorially in the contralateral vibrissal pad,bilateral hindpaws and tail.There was a negative correlation between the evoked pain in denervated area and extraterritorial areas.Microglia in the MDH of injured mice were significantly activated 3 d postoperatively.However,the activation of microglia in L4/L5 SDH occurred until 7 d postoperatively.Moreover,intraperitoneal injection of minocycline inhibited the wide-spread pain abnormalities in the vibrissal pads,hindpaws,and tail.CONCLUSION These results indicate the appearance of wide-spread neuropathic pain following infraorbital nerve transection.Microglia activation may be involved in the mechanisms of this phenomenon.     

Possible involvement of the opioid receptor gene expression in the mechanisms of the analgesic action of melatonin

In the present study, we attempt to analyse the potential involvement of the opioid receptor gene expression in the mechanisms of the analgesic action of melatonin. A trauma-pain model was established in Wistar rats by combining right - hind limb amputation with 50℃ tail - flick test. Antinociception was determined by tail-flick latency to hot waster at 50℃. Melatonin produced the antinociceptive effect in dose-dependent manner after i. p or i. c.v. administration Injected i. c. v. to rats, naloxone（10μg） obviously antagonized the antinociceptive effect induced by i.p. melatonin.     

3,4-二氯-N-甲基-N-[反式-2-(1-△3-吡咯啉基)环己基]-苯乙酰胺盐酸盐的合成及其镇痛活性的研究

3, 4-Dichloro-N-methyl-N-[trans-2- (1-△³-pyrrolinyl)-cyclohexyl]-benzenacetamide hydrochloride (K-Ⅱ) was synthesized from N-methyl-7-azabicyclo [4.1.0] heptane by treatment with 2,5-dihydropyrrole to give N-[trans-2(1-△³-pyrrolinyl)-cyclohexyl]-N-methylamine which was amidated with 3,4-dichlorophenyl-acetic acid. K-Ⅱ is an analogue of U-50488 H(K-Ⅰ), a known kappa receptor agonist.The results of animal tests showed that K-Ⅱ is 3 times as potent as K-Ⅰ as an analgesic in the mouse hot plate test and 5 times in the mouse writhing test and that the affinity of K-Ⅱ for kappa receptor may be higher than that of K-Ⅰ. The general behavioural effects of these two agents are similar in mice.     

鞘内注射大麻酚类抑制大鼠脊髓内有毒刺激引起的Fos蛋白样免疫反应及其与吗啡的比较(英文)

AIM: To determine whether cannabinoids suppressnoxious stimulu-evoked Fos protein-like immunoreac-tivity (FLI) through direct actions at the spinal level.METHODS: Rats were implanted with intrathecal(ith) catheters at least one week prior to evaluation inthe formalin test. Effects of the cannabinoid agonist,CP55,940 (80 μg ith) on formalin pain and FLI in ratspinal cord were compared with that of the prototypicnarcotic analgesic, morphine (20 μg ith). CP55, 940suppressed pain behavior and FLI induced by intra-plantar formalin. The cannabinoid suppressed Fos inthe neck region of the dorsal horn and in the ventralhorn,but not in the nucleus proprius. The efficacy ofthe cannabinoid in suppressing FLI in these laminae and     

阿片样物质介导多潘立酮和西沙必利对小鼠的镇痛作用

To study the anti-nociceptive effect of domper-idone and cisapride in mice. METHODS: Initially, the effect of these drugs on motor activity was tested using rotarod. The anti-nociception was tested using chemical and mechanical assay. In the chemical assay, the number of abdominal constrictions either in the saline treated animals or in the domperidone/cisapride (1, 5, or 10 mg/kg either po or ip) treated mice, were recorded for a period of 30 min after acetic acid challenge (10 mLAg, of 0.6 % acetic acid ip). In the tail clip assay, the time taken by the mouse to make attempts to dislodge the bulldog clamp placed at the tail (reaction time) was recorded with a cut off time of 30 s. The role of opioid pathways was examined by pretreating the animals with naloxone (1 mg/kg, ip) 30 min prior to domperidone and cisapride. RESULTS: Domperidone and cisapride, both reduced the number of abdominal constrictions when given orally or intraperitoneally. Domperidone (5 mg/kg) inhibited it to the extent of 57.0 % a     

Gabapentin effectively alleviates pain sensitization and regulates CACNA2D1 expression in postherpetic neuralgia rats北大核心CSCD

Aim To identify the molecular target of gabapentin in the treatment of postherpetic neuralgia(PHN). Methods The molecular target of gabapentin for PHN was analyzed by network pharmacology and molecular docking and confirmed by coprecipitation test. Rats were randomly divided into control group, model group, model+50 mg·kg-1 gabapentin group, model+100 mg·kg-1 gabapentin group, and model+200 mg·kg-1 gabapentin group, with nine rats in each group. The pain-related behaviors of the rats were measured at different time points. The mRNA and protein expressions of CACNA2D1, Bax, and Bcl-2 in rat spinal cord were determined by immunofluorescence, Western blot, and qPCR. Results CACNA2D1 was the target gene of gabapentin that determined via network pharmacology, molecular docking, and co-precipitation tests. After modeling, mechanical pain threshold and thermal pain threshold significantly decreased, and the number of apoptotic GABA cells significantly increased. However, after intraperitoneal injection of 50, 100, and 200 mg·kg-1 gabapentin, mechanical pain threshold and thermal pain threshold significantly increased(P<0.05), and the number of apoptotic GABA cells significantly decreased(P<0.01). Immunofluorescence and Western blot results showed that compared with the model group, with the increase of gabapentin concentration, the positive expression rate of Bax significantly decreased, and the positive expression rate of Bcl-2 and CACNA2D1 significantly increased. The mRNA expression levels of Bax, Bcl-2 and CACNA2D1 detected by qPCR were consistent with the results of immunofluorescence and Western blot. Conclusions Gabapentin up-regulates the expression of target protein CACNA2D1, inhibits the proapoptotic protein Bax, and promotes the expression of apoptotic inhibitor Bcl-2. © 2023 Publication Centre of Anhui Medical University. All rights reserved.     

生长抑素及其拮抗剂对小鼠吗啡镇痛的影响

AIM: To study the effects of somatostatin (SST) and its antagonist cyclo-(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr [Bzl]) (SSA) on morphine-induced analgesia. METHODS: The pain assays were the hot plate and the tail flick test. RESULTS: SST or SSA per se administered intracerebrally at the doses of 0.1 and 1 mg/mouse did not change the pain threshold of mice both in the hot plate and in the tail flick test. However, at the higher dose (10 mg/mouse), SST and SSA decreased the pain threshold in the tail flick test only. SST and SSA administered at the dose of 0.1 mg/mouse did not change morphine-induced analgesia. By contrast, SST and SSA at the doses of 1 and 10 mg/mouse reduced morphine analgesia effects both in the hot plate as well as in the tail flick test. CONCLUSION: Our results indicate that SSA as well as SST may be useful in studying pain mechanisms.     

半胱胺对小鼠疼痛感受的影响

INTRODUCTION Cysteamine (β-mercaptoethylamine) is a thiol com-pound whose biological activities have recently receivedgreat attention, and that can be found in animals whenacetyl coenzyme A is hydrolized by pantethinase.Clinically it has been used in the treatment ofacetaminophen poisoning and in the treatment ofnephropathic cystinosis. It was reported that cys-teamine depletes somatostatin in the stomach, duodenum,pancreas, gut and hypothalamus of rat. Cysteaminewas also found to deplete somatostatin in the brain     

精氨酸及精氨酸脱羧酶抗体对痛阈及吗啡镇痛作用的影响(英文)

目的进一步阐明胍丁胺对阿片药理作用的影响。方法采用小鼠醋酸扭体法、小鼠热辐射甩尾法、小鼠热板法评价了精氨酸及精氨酸脱羧酶抗体对痛阈、吗啡镇痛及其耐受作用的影响。结果在小鼠醋酸扭体实验中,脑室注射精氨酸能剂量依赖性地抑制小鼠扭体次数,最大抑制率达84 %。在小鼠热辐射甩尾模型中,精氨酸不影响小鼠的甩尾时间,但能剂量依赖性地增强吗啡的镇痛作用,使吗啡2 .5 mg·kg-1的最大可能镇痛百分率从23 %增加到71 %。此外,在小鼠热辐射甩尾实验中,精氨酸能抑制吗啡100 mg·kg-1所诱导的急性耐受。精氨酸上述作用可被咪唑啉受体拮抗剂咪唑克生(3mg·kg-1,ip)所抑制。在小鼠热辐射甩尾实验和小鼠55℃热板实验中,精氨酸脱羧酶抗体能抑制吗啡镇痛,并能加重吗啡所致的耐受。结论上述结果提示,精氨酸及精氨酸脱羧酶在痛阈、吗啡镇痛及吗啡依赖形成过程中具有重要作用。     

Stress-induced analgesia and morphine responses are changed in catechol-O-methyltransferase-deficient male mice

Catechol-O-methyltransferase (COMT) polymorphisms modulate pain and opioid analgesia in human beings. It is not clear how the effects of COMT are mediated and only few relevant animal studies have been performed. Here, we used old male Comt gene knock-out mice as an animal model to study the effects of COMT deficiency on nociception that was assessed by the hot plate and tail flick tests. Stress-induced analgesia was achieved by forced swim. Morphine antinociception was measured after 10 mg/kg of morphine subcutaneously. Morphine tolerance was produced with subcutaneous morphine pellets and withdrawal provoked with subcutaneous naloxone. In the hot plate test, morphine-induced antinociception was significantly greater in the COMT knock-out mice, compared to the wild-type mice. This may be due to increased availability of opioid receptors as suggested by previous human studies. In the tail flick test, opioid-mediated stress-induced analgesia was absent and morphine-induced analgesia was decreased in COMT knock-out mice. In the hot plate test, stress-induced analgesia developed to all mice regardless of the COMT genotype. There were no differences between the genotypes in the baseline nociceptive thresholds, morphine tolerance and withdrawal. Our findings show, for the first time, the importance of COMT activity in stress- and morphine-induced analgesia in mice. COMT activity seems to take part in the modulation of nociception not only in the brain, as suggested earlier, but also at the spinal/peripheral level.     

Chronic treatment with antidepressant drugs and the analgesia induced by 5-methoxy-N,N-dimethyltryptamine: attenuation by desipramine

The effect of chronic and acute oral or intraperitoneal treatment with the antidepressant drugs, desipramine, amitriptyline, alaproclate and iprindole, upon pain thresholds in the tail flick, hot plate and shock titration tests of nociception in saline- and 5-MeODMT-treated rats was studied. Chronic desipramine treatment increased the pre-test tail flick latencies. In the saline-treated rats, chronic oral desipramine treatment increased tail flick latencies, whereas chronic oral amitriptyline treatment decreased tail flick latencies. In 5-MeODMT-treated rats, chronic oral desipramine treatment attenuated the effects of 5-MeODMT (1 mg/kg) in all three tests of nociception, whereas chronic amitriptyline caused a potentiation in the tail flick and hot plate tests. Chronic oral iprindole treatment attenuated 5-MeODMT-induced analgesia in the hot plate test. Chronic intraperitoneal desipramine treatment attenuated 5-MeODMT analgesia in the tail flick and shock titration tests. In a different chronic treatment experiment, oral desipramine treatment attenuated 5-MeODMT analgesia in the tail flick test and zimeldine did for both the tail flick and hot plate tests, whereas mianserin potentiated 5-MeODMT-induced analgesia in both the tail flick and hot plate tests. In the saline-treated rats, acute treatment with all four drugs, desipramine, amitriptyline, iprindole and alaproclate, elevated the shock thresholds, whereas in 5-MeODMT-treated rats, desipramine and amitriptyline elevated shock thresholds. Two main conclusions can be drawn: chronic desipramine caused a quite consistent attenuation of 5-MeODMT-induced analgesia and the effects of acute treatment differed strongly from that of the chronic treatment. The effects of chronic administration with these antidepressants were compared with other findings using different measures of behavioural and receptor function.     

Effect of homotaurine in experimental analgesia tests.

1. The possible antinociceptive action of GABA A receptor agonist homotaurine, has been studied through a battery of chemical (acetic acid) and thermal (hot plate, tail flick and tail immersion) tests in rats and mice. 2. The aminoacid was used at the following doses 22.25; 55.62 and 111.24 mg/kg i.p. and 50-100 micrograms i.c.v.; and measurements were made at the time of and at 5, 15 and 30 min after drug administration. 3. Homotaurine exhibited a significantly antinociceptive effect in all the above mentioned test except hot plate and when administered i.c.v. in the tail flick test. 4. The antinociceptive effect in the chemical test was dose and time dependent. 5. In the tail immersion test, latency time for withdrawal of the tail was significantly increased with the dose of 55.62 mg/kg at 15 min and 111.24 mg/kg at 30 min. 6. In the tail flick test the antinociceptive effect was dose dependent at 15 and 30 min. 7. From the above results the implication of peripheral and spinal mechanisms in the antinociceptive effect of homotaurine may be concluded.     

天蟾胶囊镇痛作用的实验研究

目的：考察天蟾胶囊对大鼠、小鼠的镇痛作用。方法：采用小鼠醋酸扭体反应、小鼠热板法镇痛试验、大鼠甩尾法镇痛试验及对大鼠三叉神经痛的镇痛实验。结果：天蟾胶囊能显著抑制小鼠热板、扭体反应及大鼠甩尾反应，提高大鼠三叉神经痛阈。给药起效时间约30min，作用峰值在给药后120min。天蟾胶囊的镇痛效果随剂量的加大而增强，但该药的早期作用(药后15～60min)弱于阳性对照药哌替啶。结论：天蟾胶囊对实验大鼠、小鼠具有明显的镇痛作用。     

Complete Blockade and Attenuation of 5–Hydroxytryptamine Induced Analgesia Following NA Depletion in Rats and Mice

Abstract: The effect of pretreatment with the noradrenaline neurotoxin, N–2–chloroethyl–N–ethyl–2–bromobenzylamine (DSP4), upon the analgesia induced by various doses of 5–hydroxytryptamine (5–HT) was examined in rats and mice. DSP4 treatment (2 × 50 mg/kg, intraperitoneally) of rats caused a complete blockade of 5–HT induced analgesia in the tail–flick, hot–plate and shock titration tests. DSP4 treatment (1 × 50 mg/kg, intraperitoneally) of mice caused a partial blockade of 5–HT induced analgesia in the hot–plate test, but no significant blockade in the tail–flick test. These results are discussed with regard to serotonergicnoradrenergic interactions and the species discrepancy in nociceptive testing     

Attenuation of pethidine-induced antinociception by zimelidine, an inhibitor of 5-hydroxytryptamine reuptake

1 The effect of selective inhibition of 5-hydroxytryptamine (5-HT) re-uptake by fluoxetine and zimelidine on morphine- and pethidine-induced antinociception was studied in rats. The hot plate (55 degrees C) and tail flick test procedures for measurement of analgesia were employed to assess antinociception. 2 Pretreatment with fluoxetine and zimelidine potentiated the antinociceptive effect of morphine (4.5 mg/kg, as base); zimelidine was without effect on a lesser dose of morphine (3.0 mg/kg, as base). 3 Pretreatment with zimelidine but not fluoxetine, significantly attenuated pethidine-induced antinociception (24 mg/kg, as base) and prevented the expression of pethidine-induced antinociception at a lesser 10 mg/kg (as base) dose of pethidine. 4 These and other results support (a) a role for 5-HT in the expression of morphine-induced antinociception, and (b) a different mode of antinociceptive action of morphine and pethidine. The role of 5-HT in pethidine-induced antinociception remains unclear.     

The effect of diazepam on nociception in mice

The antinociceptive properties of diazepam were evaluated in mice, using four different pain tests and different doses of the drug (0.2, 0.5, 1.0 and 2.0 mg/kg). In the tail flick test and the increasing temperature hot plate test there were no effects. In the formalin test reduced licking was observed for the highest dose of diazepam. However, this dose also induced clear sedation possibly causing the reduced licking response. In the constant temperature hot plate test a hyperalgesia was found for all doses tested. This hyperalgesia was not observed in animals adapted to the test apparatus, suggesting that the "hyperalgesic" effect of diazepam may be due to reduced stress analgesia. The serum concentrations of the drug were comparable to therapeutic levels in humans. It was concluded that the sedative and anxiolytic effects of diazepam may influence the results of nociceptive tests, but the drug has probably no effect on nociception in itself.