Analgesic and anti-inflammatory activity of Cotinus coggygria Scop.extracts in vivo

Objective:To assess the analgesic and anti-inflammatory effects of standardized extract of Cotinus coggygria(C.coggygria)in different animal models.Methods:C.coggygria extracts(25,50,and 100 mg/kg)were administered to rats and mice(n=6)during hot plate,tail-flick,acetic acid-induced writhing,and formalin tests to determine its analgesic efficacy.The anti-inflammatory activity of C.coggygria extracts was evaluated by histamine and carrageenan-induced paw edema,cotton pellet-induced granuloma,and acetic acid-induced peritoneal capillary dye leakage tests.Results:C.coggygria extracts(50 and 100 mg/kg)significantly alleviated thermal and chemical-induced pain in rodents(P<0.05).It also demonstrated notable anti-inflammatory properties by mitigating histamine and carrageenan-induced paw edema,granuloma deposits,and vascular permeability(P<0.05).Moreover,C.coggygria extracts remarkably reduced TNF-α,IL-1β,IL-6,COX-2,and oxidative stress in rat paws(P<0.05).Carrageenan-induced histological aberrations in hind paw tissues were effectively(P<0.05)mitigated by treatment with C.coggygria extracts.Conclusions:C.coggygria Scop.extracts show analgesic and anti-inflammatory effects via inhibition of COX-2 and inflammatory and oxidative mediators.

Phytochemical and Pharmacological Study on the Dry Extract of Matricaria discoidea DC. herb and Its Amino Acids Preparations

Pineappleweed(Matricaria discoidea DC.,Asteraceae)herb is an essential oil containing raw material with spasmolytic and anti-inflammatory activity.It is also rich in phenolics,which may be used in pharmaceutical practice.This study aimed to investigate the phenolic and amino acid composition and the hyporific and analgesic effects of the M.discoidea aqueous-ethanolic extract and its amino acid modifications.In addition,we developed a polyethylene oxide gel formulation with M.discoidea extracts for the 3D-printed oral solid dosage preparations.In M.discoidea extracts,16 phenolic substances and 14 amino acids were established.The extract and its amino acid preparations revealed both analgesic and soporific activity in the studies with rodents.Amino acids enhanced these effects.Arginine,β-alanine,glycine,valine,and lysine potentiated the analgesic activity by 27%–64%,whileβ-alanine,glycine,and valine increased the soporific activity by 136%,176%,and 129%,respectively.The composition of the polyethylene oxide(PEO)printing gel with the M.discoidea extract was developed,and its printability was confirmed.The proposed 3D-printed medicines could be implemented for sleep disorders and painful conditions.

Pain management in chronic pancreatitis

Pain in chronic pancreatitis(CP)is difficult to manage.Many patients suffer from inadequate pain relief,completely incapacitating them in their daily activities.Historically,despite their well-known adverse effects,opioids have been the pillar of treatment regimens in painful CP.The management is now gradually evolving with a better understanding of the underlying pathophysiology of CP-related pain.Clinicians should follow a holistic approach to the management of CPassociated pain,which must involve lifestyle changes that are coupled with analgesic medications and other pain-relieving interventions.Furthermore,there is no easy cure for vanquishing CP-associated pain.Each patient must be evaluated on a case-by-case basis by a multidisciplinary team to decide which treatment option is best suited for that individual.

Anticancer,Anti-inflammatory,Analgesic,and Anxiolytic Effects of Koumine and Their Molecular Mechanisms

Koumine is an indole alkaloid monomer extracted from the Chinese herb Gelsemium elegans,which has a variety of pharmacological effects.This paper provides a comprehensive summary of the pharmacological effects and molecular mechanisms of koumine,with a particular emphasis on its mechanisms of action in the context of anticancer,anti-inflammatory,analgesic,and anxiolytic properties.The aim is to provide a theoretical foundation for further research and the application of koumine in clinical practice.

Quasi-Static, Poiseuille Flow of Analgesics from an Elastomeric Pump: Theoretical Determination of Infusion Times and Toxicity Conditions

Background: Elastomeric pumps (elastic balls into which analgesics or antibiotics can be inserted) push medicines through a catheter to a nerve or blood vessel. Since elastomeric pumps are small and need no power source, they fit easily into a pocket during infusion, allowing patient mobility. Elastomeric pumps are widely used and widely studied experimentally, but they have well-known problems, such as maintaining reliable flow rates and avoiding toxicity or other peak-and-trough effects. Objectives: Our research objective is to develop a realistic theoretical model of an elastomeric pump, analyze its flow rates, determine its toxicity conditions, and otherwise improve its operation. We believe this is the first such theoretical model of an elastomeric pump consisting of an elastic, medicine-filled ball attached to a horizontal catheter. Method: Our method is to model the system as a quasi-Poiseuille flow driven by the pressure drop generated by the elastic sphere. We construct an engineering model of the pressure exerted by an elastic sphere and match it to a solution of the one-dimensional radial Navier-Stokes equation that describes flow through a horizontal, cylindrical tube. Results: Our results are that the model accurately reproduces flow rates obtained in clinical studies. We also discover that the flow rate has an unavoidable maximum, which we call the “toxicity bump”, when the radius of the sphere approaches its terminal, unstretched value—an effect that has been observed experimentally. Conclusions: We conclude that by choosing the properties of an elastomeric pump, the toxicity bump can be restricted to less than 10% of the earlier, relatively constant flow rate. Our model also produces a relation between the length of time that the analgesic fluid infuses and the physical properties of the fluid, of the elastomeric sphere and the tube, and of the blood vessel into which the analgesic infuses. From these, we conclude that elastomeric pumps can be designed, using our simple model, to control infusion times while avoiding toxicity effects.

Analgesic Effect of Combined Spinal-Epidural Anesthesia and its Effect on TNF-α and CRP Levels in Elderly Patients with Hip Fracture During Surgical Treatment

Objective:To observe the analgesic effect of combined spinal and epidural anesthesia on older patients undergoing hip fracture surgery.Method:One hundred and twenty elderly hip fracture surgery patients treated in our hospital from January 2021 to December 2022 were selected and randomly divided into two groups,with 60 cases in the experimental group and 60 in the control group.The experimental group was given combined spinal-epidural anesthesia intervention measures,while the control group was given epidural anesthesia intervention measures.The analgesic effect,tumor necrosis factor-alpha(TNF-α),C-reactive protein(CRP)levels,and other observation indicators were analyzed after anesthesia intervention.Result:After the intervention,the analgesic effect and the evaluation results of the subjects in the experimental group were better than those in the control group(P<0.05);the obtained values of TNF-αand CRP levels in the experimental group were higher than those of the control group(P<0.05).Conclusion:The combined spinal-epidural anesthesia intervention demonstrated positive outcomes.The analgesic effect of patients during surgery and their inflammatory factor levels improved,which makes this intervention worthy of clinical application and promotion.

电针对佐剂性关节炎大鼠脾细胞IL-1和IL-2活性的影响

To seek for peripheral mechanism of electroacupuncture (EA) analgesia, observed effects of EA on activity of IL 1 and IL 2 in spleem cell in adjuvant arthritic (AA) rats of inflammatory pain model. METHODS Injected Freund’s complete adjuvant into the right hind paw of rats to produce AA model, stimulated Xuanzhong and Kunlun points with EA, adpoted H3 TdR and MTT methods to detect activity of IL 1 and SIL 2. RESULTS EA may raise activity of IL 1 and IL 2 in spleen cell in AA rats while Eaamalgesia. CONCLUSION The peripheral action of EA amalgesia on inflammatory pain is related to rising of IL 1 amd IL 2 activity.

Synthesis and analgesic activities studies on bispiperazinium (BPZ) salts

Selecting compound 97-9-G4 as lead compound, a series of bispiperazinittm salts 5a-h were designed, synthesized and evaluated for their analgesic activities. The results show that phenylethyl group of 97-9-G4 is a crucial pharmacophore; the intro- duction of electron-withdrawing group on benzene ring is favorable to the activity.

N-[反式-2-(3,4-~3H-吡咯基)-环己基]-N-甲基-3,4-二氯-苯乙酰胺盐酸盐的合成

N-[反式-2-(1-吡咯基)环己基]-N-甲基-3,4-二氯-苯乙酰胺盐酸盐(简称U-50488H(K-I))是近年来报道的高选择性的K-阿片受体激动剂,动物实验结果表明:该化合物具有较强的镇痛活性,且成瘾性较低,呼吸抑制较弱,无吗啡样副作用的新型麻醉镇痛剂。为研究它的药理作用,我们用氚标记了U-50488(K-I)。合成该化合物开始原料是N-甲基-反式-2-(1-△~3-吡咯啉基)环己基胺,按一般还原法以氧化铂为催化剂,通氚进行氚化反应,未经分离与3,4一二氯苯乙酸在二环己基碳二亚胺(DCC)存在下进行缩合脱水反应,生成N-[反式-2-(3,4-~3H-吡咯基)环己基]-N-甲基-3,4-二氯-苯乙酰胺,再用氯化氢乙醚处理,制得了氚化的U-50488(K-I)。合成途径如下:

Comparison of the analgesic effects between electro-acupuncture and moxibustion with visceral hypersensitivity rats in irritable bowel syndrome

AIM To observe whether there are differences in the effects of electro-acupuncture(EA) and moxibustion(Mox) in rats with visceral hypersensitivity. METHODS EA at 1 m A and 3 m A and Mox at 43?℃ and 46?℃ were applied to the Shangjuxu(ST37, bilateral) acupoints in model rats with visceral hypersensitivity. Responses of wide dynamic range neurons in dorsal horns of the spinal cord were observed through the extracellular recordings. Mast cells(MC) activity in the colons of rats were assessed, and 5-hydroxytryptamine(5-HT), 5-hydroxytryptamine 3 receptor(5-HT3R) and 5-HT4Rexpressions in the colons were measured.RESULTS Compared with normal control group, responses of wide dynamic range neurons in the dorsal horn of the spinal cord were increased in the EA at 1 m A and 3 m A groups(1 m A: 0.84 ± 0.74 vs 2.73 ± 0.65, P < 0.001; 3 m A: 1.91 ± 1.48 vs 6.44 ± 1.26, P < 0.001) and Mox at 43?℃ and 46?℃ groups(43?℃: 1.76 ± 0.81 vs 4.14 ± 1.83, P = 0.001; 46?℃: 5.19 ± 2.03 vs 7.91 ± 2.27, P = 0.01). MC degranulation rates and the expression of 5-HT, 5-HT3 R and 5-HT4 R in the colon of Mox 46?℃ group were decreased compared with model group(MC degranulation rates: 0.47 ± 0.56 vs 0.28 ± 0.78, P < 0.001; 5-HT: 1.42 ± 0.65 vs 7.38 ± 1.12, P < 0.001; 5-HT3R: 6.62 ± 0.77 vs 2.86 ± 0.88, P < 0.001; 5-HT4R: 4.62 ± 0.65 vs 2.22 ± 0.97, P < 0.001). CONCLUSION The analgesic effects of Mox at 46?℃ are greater than those of Mox at 43?℃, EA 1 m A and EA 3 m A.

Drainage after total thyroidectomy or lobectomy for benign thyroidal disorders

Objective: This prospective randomized clinical trial was conducted to evaluate the necessity of drainage after total thyroidectomy or lobectomy for benign thyroidal disorders. Methods: A total of 116 patients who underwent total thyroidectomy or lobectomy for benign thyroidal disorders were randomly allocated to be drained or not. Operative and postoperative outcomes including operating time, postoperative pain assessed by visual analogue scale (VAS), total amount of intramuscular analgesic administration, hospital stay, complications, necessity for re-operation and satisfaction of patients were all assessed. Results: The mean operating time was similar between two groups (the drained and non-drained groups). The mean VAS score was found to be significantly low in the non-drained group patients in postoperative day (POD) 0 and POD 1. The mean amount of intramuscular analgesic requirement was significantly less in the non-drained group. One case of hematoma, two cases of seroma and three cases of transient hypoparathyroidism occurred in the non-drained group, whereas one case of hematoma, two cases of seroma, two cases of wound infections and two cases of transient hypoparathyroidism occurred in the drained group. No patient needed re-operation for any complication. The mean hospital stay was significantly shorter and the satisfaction of patients was superior in the non-drained group. Conclusion: These findings suggest that postoperative complications cannot be prevented by using drains after total thyroidectomy or lobectomy for benign thyroid disorders. Furthermore, the use of drains may increase postoperative pain and the analgesic requirement, and prolong the hospital stay. In the light of these findings, the routine use of drains might not be necessary after thyroid surgery for benign disorders.

Analgesic and anti-inflammatory activities of Passiflora foetida L.

Objective:To investigate the analgesic and anti-inflammatory activities of ethanol extract of Passiflora foetida(P.foetida) leaves.Methods:Ethanol extract of P.foetida leaf was evaluated for analgesic action by acetic acid-induced writhing and hot plate method in albino mice.The anti-inflammatory property of ethanolic leaf extract was tested by carrageenan induced acute paw edema and histamine induced acute paw edema in rats.Results:The dose 200 mg/kg of P. foetida leaf extract exhibited highest significant analgesic activity[(13.50±0.43) min]at a reaction time of 20 min in hot plate method in mice.The ethanol extract of leaf dose 100 mg/kg produced a highly significant anti inflammatory effect[(1.302±0.079) mL]in rats.Conclusions:It is very clear that P.foetida also has analgesic and anti-inflammatory activities for the pharmaceuticals.

Analgesic,anti-inflammatory and anti-diarrheal activities of ethanolic leaf extract of Typhonium trilobatum L.Schott

Objective:To explore the efficacy of ethanolic leaf extract of Typhonium trilobatum L.Schott in treating diarrhea,pain and inflammation using experimental models.Methods:In the present study,acetic acid-induced writhing,xylene-induced ear edema and castor oil-imluced diarrlieal model were used to evaluate the analgesic,anti-inflammatory and anti-diarrheal activities,respectively.Acute toxicity test was carried out to fix the safe doses of the plant extract.Results:The plant extract demonstrated a significant inhibition of writhing(P<0.01)compared with the control group in acetic acid-induced writhing test in mice.The extract also significantly inhibited the xylene induced ear edema formation(P<0.05).In anti-diarrheal test,the extract significantly decreased the frequency of defecation and increased the mean latent period(P<0.0l)in castor oil-induced diarrheal model mice at the doses of 250 and 500 mg/kg body weight.Conclusions:These results suggest that the extract possesses significant analgesic,anti-inflammatory and anti-diarrheal activities that support to the ethnopharmacologicl uses of this plant.

Controlled-Release Oxycodone Alone or Combined with Gabapentin for Management of Malignant Neuropathic Pain

Objective： To evaluate the analgesic efficacy of controlled-release （CR） oxycodone and gabapentin in malignant neuropathic pain （NP）. Methods： Patients with malignant NP were enrolled and baseline pain intensity （PI） was recorded. They initially took one week CR oxycodone and were allocated to two different groups at day 8 by reevaluated PI. Patients with mild pain went to CR oxycodone mono-therapy group （OO group） and took another two weeks CR oxycodone. Others went to （CR oxycodone combined gabapentin group （OG group） and received additional gabapentin. Daily doses and side effects were recorded. Results： Fifty-eight （92.06%） of the 63 enrolled patients completed the initial week＇s therapy. Twenty-two （37.93%） went to OO group and PI significantly reduced at day 15 （2.00 vs. 2.62, P=0.004）, but not improved at day 22 （1.90 vs. 2.00, P=0.54）. Thirty-six （62.07%） patients went to OG group and PI was significantly reduced at day 15 （4,47 vs. 2.94, P〈0.001）, but not improved at day 22 （2.94 vs. 2.75, P=0.136）. Mean daily dose （MDD） of CR oxycodone at day 8 was 62.64 mg. It was significantly increased at days 15 and 22 （71.43 mg vs. 62.64 rag, P=0.021; 81.90 mg vs. 71.43 mg, P=0.004） in OO group. MDD of gabapentin was significantly increased at day 22 compared to day 15 （862.50 mg vs. 993.75 mg, P〈0.001）. Constipation was occurred in 13.64% of the patients in OO group and 14.26 % in OG group. Conclusion： Malignant NP may be well controlled by oxycodone mono-therapy. Early combination with gabapentin is sensible when pain is not satisfactory relieved by oxycodone alone. The side effects of them are manageable.

Analgesic and anti-inflammatory activities of the ethanol extract of the leaves of Helianthus Annus in Wistar rats

Objective:To investigate the anti-inflammatory and analgesic effects of the ethanol extract of leaves of Helianthus annus L.(H.annus) in acclimatized Wistar rats.Methods:It was undertaken using the albumin induced paw edema model of inflammation as well as both the hotplate and tail immersion analgesic test methods.Doses of the extract tested in experimental rats were 0.5 g/kg,2 g/kg and 4 g/kg while negative and positive control rats received distilled water and indomethacin respectively.Results:It was shown that treatment with the tested doses of the extract effectively inhibited paw edema induced by egg albumin.This effect was comparable if not better than the observations made in rats treated with 10 mg/kg of indomethacin orally.Treatment with the extract was also observed to have significantly increased the mean tolerance time of rats to thermal noxious stimuli compared to control animals that had distilled water and appeared to be more effective than 10 mg/kg of indomethacin treatment.Conclusions: These observations confirmed the presence of a strong anti-inflammatory and anti-noiciceptive activity in the ethanol extract of the leaves of H.annus and therefore validated the folkloric use of the leaves of this plant in treatment of pro-inflammatory,post traumatic situations.

Pharmacological and biomedical properties of sea anemones Paracondactylis indicus,Paracondactylis sinensis,Heteractis magnifica and Stichodactyla haddoni from East coast of India

Objective:To explore the biomedical and pharmacological activity of Paracondactylis indicus (P.indicus).Paracondactylis sinensis(P.sinensis).Heteraclis magnified(H.magnified) and Stichadactyla haddoni(S.haddoni).Methods:The live sea anemones were kept inside the glass howl along with some amount of distilled water in an ice container for 15 min.During stress Condition,nemalocysts released from the tentacles were collected and centrifuged al 5 000 rpm for 15 min.The supernatant were collected ill separate cleaned beakers for lyophilisation.Results: The protein content of crude extracts was 15.2.28.7.18.2 and 35.4μg/mL.In hemolytic assay,the P.indicus was sensitive(16.842 HT/mg) on chicken blood but P.sinensis was less sensitive(1.114 HT/mg) on chicken and goal blood.Whereas H.magnified and S.haddoni showed hemolysis (0.879.0.903 HT/mg and 56.263.0.451 HT/mg) in chicken and goat blood.In antimicrobial assay, the methanol extract of P.indicus showed maximum inhibition zone of 9.7 mm against S.typhii and P.sinensis showed 9.8 mm against K.pneumonia in methanol and ethanol extracts.Whereas the H.magnified and S.haddoni showed maximum of 10 mm against S.typhii.K.pneumonia in methanol and ethanol extracts.Conclusions:The high toxic sea anemones may also contain some biologically active agents which has haemolytic,analgesic and anti-infilamatory activity.

Analgesic effect of parecoxib combined with ropivacaine in patients undergoing laparoscopic hepatectomy

BACKGROUND Currently, there is no uniform standard for analgesia during laparoscopic hepatectomy. Most of the analgesia schemes adopt epidural analgesia after laparotomy. Although the analgesia is effective, it has a great impact on the recovery of patients after laparoscopic hepatectomy and is not completely suitable for analgesia after laparoscopic hepatectomy. Although multimodal perioperative analgesia can significantly relieve postoperative pain, there is no relevant study of parecoxib combined with ropivacaine for post-laparoscopic hepatectomy analgesia.AIM To study the analgesic effect of the preoperative intravenous injection of parecoxib combined with long-acting local anesthetic ropivacaine for incision infiltration in patients undergoing laparoscopic hepatectomy.METHODS Forty-eight patients undergoing laparoscopic hepatectomy were randomly divided into a combined group (parecoxib combined with ropivacaine) and a control group. The visual analogue scale (VAS) at rest and during movement was used to compare the analgesic effect of the two groups. Meanwhile, the cumulative sufentanil, the recovery time for enterokinesia, the length of postoperative hospital stay, and the adverse reactions (nausea and vomiting)were recorded and compared between the two groups.RESULTSThe change tendency in VAS scores for both groups was similar after operation.At rest, the VAS scores of the combined group were significantly lower than those of the control group at 0, 6, 12, 24 and 36 h, and during movement, the VAS scores of the combined group were significantly lower than those of the control group at 0, 6, 12, and 24 h. The recovery time for enterokinesia in the combined group was 2.9 d, which was significantly shorter than that in the control group.The cumulative sufentanil in the combined group decreased significantly at 24,36, and 48 h after operation.CONCLUSION Preoperative intravenous injection of parecoxib combined with ropivacaine for incision infiltration is a simple and effective method for postoperative analgesia in laparoscopic hepatectomy, which could relieve pain and promote recovery.

Sedation and monitoring for gastrointestinal endoscopy

The safe sedation of patients for diagnostic or therapeutic procedures requires a combination of properly trained physicians and suitable facilities.Additionally,appropriate selection and preparation of patients,suitable sedative technique,application of drugs,adequate monitoring,and proper recovery of patients is essential.The goal of procedural sedation is the safe and effective control of pain and anxiety as well as to provide an appropriate degree of memory loss or decreased awareness.Sedation practices for gastrointestinal endoscopy(GIE) vary widely.The majority of GIE patients are ambulatory cases.Most of this procedure requires a short time.So,short acting,rapid onset drugs with little adverse effects and improved safety profiles are commonly used.The present review focuses on commonly used regimens and monitoring practices in GIE sedation.This article is to discuss the decision making process used to determine appropriate pre-sedation assessment,monitoring,drug selection,dose of sedative agents,sedation endpoint and post-sedation care.It also reviews the current status of sedation and monitoring for GIE procedures in Thailand.

Extracellular signal-regulated kinase, substance P and neurokinin-1 are involved in the analgesic mechanism of herb-partitioned moxibustion

Herb-partitioned moxibustion can effectively mitigate visceral pain, a major symptom in inflammatory bowel disease, but the analgesic lnechanism is still unclear. Moreover, extracellular signal-regulated kinase, substance P, and neurokinin-1 are involved in formation of central hyperalgesia. Thus, we postulated that the analgesic effect of herb-partitioned moxibustion may be associated with these factors. Accordingly, in this study, we established an inflammatory bowel disease visceral pain model in rat by enema with a mixed solution of 5% trinitrobenzenesulfonic acid and 50% ethanol. Bilateral Tianshu （ST25） and Qihai （CV6） points were selected for herb-partitioned moxi- bustion. Our results showed that herb-partitioned moxibustion improved visceral pain and down-regulated extracellular signal-regulated kinase, substance P, and neurokinin-1 protein and mRNA expression in dorsal root ganglia. These results indicate that down-regulation of extracellular signal-regulated kinase, substance E and neurokinin-1 protein and mRNA may be a central mechanism for the analgesic effect of herb-partitioned moxibustion.

Hyperammonemia,brain edema and blood-brain barrier alterations in prehepatic portal hypertensive rats and paracetamol intoxication

AIM:To study the blood-brain barrier integrity,brain edema, animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication. METHODS:Adults male Wistar rats were divided into four groups.Group Ⅰ:sham operation;Ⅱ:Prehepatic portal hypertension,produced by partial portal vein ligation;Ⅲ: Acetaminophen intoxication and Ⅳ:Prehepatic portal hypertension plus acetaminophen.Acetaminophen was administered to produce acute hepatic injury.Portal pressure,liver serum enzymes and ammonia plasma levels were determined.Brain cortex water content was registered and trypan blue was utilized to study blood brain barrier integrity.Reflexes and behavioral tests were recorded. RESULTS:Portal hypertension was significantly elevated in groups Ⅱ and Ⅳ.Uver enzymes and ammonia plasma levels were increased in groups Ⅱ,Ⅲ and Ⅳ.Prehepatic portal hypertension (group Ⅱ),acetaminophen intoxication (group Ⅲ) and both (group Ⅳ) had changes in the blood brain-barrier integrity (trypan blue) and hyperammonemia.Cortical edema was present in rats with acute hepatic injury in groups Ⅲ and Ⅳ.Behavioral test (rota rod) was altered in group Ⅳ. CONCLUSION:These results suggest the possibility of another pathway for cortical edema production because blood brain barrier was altered (vasogenic) and hyperammonemia was registered (oltotoxic).Group Ⅳ,with behavioral altered test,can be considered as a model for study at an early stage of portal-systemic encephalopathy.