A Case of Acute Withdrawal Symptoms Due to Unplanned Interruption of Buprenorphine Transdermal Patch: With a Discussion Including Social Aspects of Home Medical Care Patients

Introduction: Since the commercial availability of buprenorphine extended-release transdermal patches (BTDP) from the early 2010’s, the therapeutic indications for opioids have widely expanded to include chronic benign diseases. We report a case of a home health care patient with acute opioid withdrawal symptoms due to self-interruption of BTDP. Case: An 84-year-old man using home health care services due to worsening of lumbar spinal canal stenosis had been receiving analgesia with a BTDP, a mixed opioid agonist/antagonist analgesic, for the preceding five months. Since the patient's spouse thought that his pain and symptoms were gradually improving, she secretly replaced the BTDP with an NSAID patch without informing the patient. About 50 hours later, the patient experienced a variety of symptoms, including frequent urination with incontinence every five minutes, watery diarrhea, sweating, decreased blood pressure, discomfort in the feet, and insomnia. Evaluation of the Clinical Opiate Withdrawal Score (COWS) by the home health care physician indicated a score of 12, corresponding to mild withdrawal symptoms. About 12 hours after symptom onset, the severe abnormalities were barely noticeable and completely disappeared after two days. Conclusion: Few previous case reports have described withdrawal symptoms due to rapid discontinuation of BTDP. In addition to the medical considerations, we report the social issues associated with onset of the condition in a home environment. Opioid use for non-cancer pain requires medication management from a different perspective than that for cancer pain.

SUN's abdominal acupuncture for depression after methamphetamine withdrawal: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical effect of SUN 's abdominal acupuncture and conventional acupuncture in the treatment of depression after methamphetamine withdrawal.@*METHODS@#A total of 80 female patients with depression after methamphetamine withdrawal were randomly divided into an observation group (40 cases, 1 case dropped off) and a control group (40 cases, 2 cases dropped off). The control group was treated with conventional acupuncture at Baihui (GV 20), Yintang (GV 29), Taichong (LR 3), Shenmen (HT 7), Neiguan (PC 6), Danzhong (GV 17), and the observation group was treated with SUN 's abdominal acupuncture at area 1 of the abdomen and area 8 of the abdomen. Both groups were treated once a day, 30 min each time, 6 days as a course of treatment, 1 day rest between treatment courses, a total of 4 courses of treatment. The scores of withdrawal symptoms, Hamilton depression scale (HAMD), Pittsburgh sleep quality index (PSQI) scale and serum serotonin (5-HT) level were compared between the two groups before and after treatment.@*RESULTS@#After treatment, the scores of withdrawal symptoms, HAMD and the various scores and total score of PSQI scale in the two groups were all lower than before treatment (P<0.01), and the scores of withdrawal symptoms, HAMD and the sleep quality, time to fall asleep, sleep time scores and total score of PSQI in the observation group were lower than the control group (P<0.05, P<0.01). After treatment, the serum 5-HT level of the two groups was increased (P<0.01), and that in the observation group was higher than the control group (P<0.05).@*CONCLUSION@#SUN 's abdominal acupuncture can improve withdrawal symptom, depression and sleep quality, increase serum 5-HT content in treatment of depression after methamphetamine withdrawal, and has better effect than conventional acupuncture.

Chemical composition of Zhumeria majdae essential oil and its effects on the expression of morphine withdrawal syndrome and tolerance to the anticonvulsant effect of morphine on pentylenetetrazole-induced seizures in mice / Composição química do óleo essencial de Zhumeria majdae e seus efeitos na expressão da síndrome de abstinência de morfina e tolerância ao efeito anticonvulsivante da morfina em crises induzidas por pentilenotetrazol em camundongos

Abstract Regarding the proven anticonvulsant effect of Zhumeria majdae essential oil (ZMEO) in previous studies we were prompted to investigate the ZMEO effects on the tolerance to the anticonvulsant effects of morphine and the morphine withdrawal syndrome. Tolerance to the morphine anticonvulsant effect was induced in mice by subcutaneous injection of 2.5 mg/kg of morphine for 4 days. Subsequent doses of ZMEO (20 mg/kg) were used to study the expression and development of morphine tolerance. Clonidine was used as the standard drug to inhibit the morphine withdrawal syndrome symptoms. To study the ZMEO effect on withdrawal syndrome, mice received appropriate morphine values for 4 days and on the fifth day, 60 min before administration of naloxone. The effective dose of ZMEO was determined and the number of jumps, stands and changes in the dry stool weight, as symptoms of withdrawal syndrome were evaluated. The dose of 20 mg/kg of ZMEO decreased the tolerance in development and expression groups significantly. Counting the number of jumping, standing and defecation were assessed 30 min after morphine and 1 h after the vehicle and clonidine. The dose of 40 mg/kg ZMEO decreased all the signs of withdrawal syndrome significantly. ZMEO was analyzed by GC/MS and linalool (53.1%) and camphor (23.8%) were characterized as the main components. The results suggest that ZMEO possesses constituent(s) that have activity against tolerance to the anticonvulsant effects of morphine and the morphine withdrawal symptoms.

Resumo Em relação ao efeito anticonvulsivante comprovado do óleo essencial de Zhumeria majdae (ZMEO) em estudos anteriores, fomos instigados a investigar os efeitos do ZMEO em relação à tolerância aos efeitos anticonvulsivantes da morfina e da síndrome de abstinência de morfina. A tolerância ao efeito anticonvulsivante da morfina foi induzida em camundongos por injeção subcutânea de 2,5 mg/kg de morfina por 4 dias. Doses subsequentes de ZMEO (20 mg/kg) foram utilizadas para estudar a expressão e o desenvolvimento da tolerância à morfina. A clonidina foi usada como droga padrão para inibir os sintomas da síndrome de abstinência da morfina. Para estudar o efeito do ZMEO na síndrome de abstinência, os camundongos receberam valores apropriados de morfina por 4 dias e, no 5º dia, 60 minutos antes da administração de naloxona. A dose efetiva de ZMEO foi determinada, e o número de saltos e de permanência e as alterações no peso das fezes secas, conforme os sintomas da síndrome de abstinência, foram avaliados. A dose de 20 mg/kg de ZMEO diminuiu significativamente a tolerância nos grupos de desenvolvimento e expressão. A contagem do número de saltos, permanência e defecação foi avaliada 30 minutos após a morfina e 60 minutos após o veículo e a clonidina. A dose de 40 mg/kg de ZMEO diminuiu significativamente todos os sinais da síndrome de abstinência. O ZMEO foi analisado por GC/MS, e linalol (53,1%) e cânfora (23,8%) foram caracterizados como os principais componentes. Os resultados sugerem que o ZMEO apresenta constituintes que possuem atividade contra a tolerância aos efeitos anticonvulsivantes da morfina e aos sintomas de abstinência da morfina.

SMOKING CESSATION – A PRACTICAL PARADIGM FOR DOCTORS

@#Helping people to stop smoking is a highly cost-effective and an important means of preventing cardiovascular disease such as ischemic heart disease and stroke. A doctor who fails to provide smoking cessation counselling to a patient who smokes is no better than a doctor who neglects to prescribe a cholesterol – lowering drug. Many smokers want to stop smoking, and others may be receptive to encouragement to stop. As doctors, we are in a unique position to help our patients stop smoking because our advice on health matters is trusted more than anyone else’s (or so we should hope to think). This article was first published in the Singapore Family Physician in 2008, and focuses on what a doctor should do with a patient who smokes. An additional update on alternatives to cigarettes has been added.

Time Course Of Cigarette Withdrawal Symptoms While Using Nicotine Patch During Ramadan / Jurnal Sains Kesihatan Malaysia

Previous studies explain the time course of withdrawal symptoms among smokers pre and post quit attempt, either withor without the help of medication. Studies showed that male Muslim smokers could quit smoking during Ramadan sincefasting relate to the changes in psychosomatic, daily activities and nicotine withdrawal symptoms. This study aimed toinvestigate the time course of withdrawal symptoms among smokers who used nicotine patch to quit smoking duringfasting in Ramadan. A total of 40 eligible Muslim males who tried to quit smoking was selected and provided with smokingcessation counseling for the duration of 8 to 10 weeks while on nicotine patch. Participants level of withdrawal symptomswas recorded by using nine items of Minnesota Nicotine Withdrawal Scale over a period of 60 days. Participant’s carbonmonoxide reading and body weight were measured within six months including pre and post-Ramadan fasting. Over fourweeks of the fasting month, the measured withdrawal symptoms such as urge to smoke (P ≤ 0.001), depressed mood (P≤ 0.001), irritability/frustration or anger (P ≤ 0.05), anxiety (P ≤ 0.05), difficulty concentrating(P ≤ 0.001), restlessness(P ≤ 0.001), difficulty going to sleep (P ≤ 0.001) and impatient (P ≤ 0.05) significantly decreased except appetite by theend of week 4. Time course analyses demonstrated that all outcome measures showed good effects during cessation infasting month. The point prevalence abstinence at first month of quitting was 67.5% which is higher in fasting month.This has shown positive clinical implications in managing smoking cessation program during Ramadan with the aid ofnicotine patch.

Chemical composition of Zhumeria majdae essential oil and its effects on the expression of morphine withdrawal syndrome and tolerance to the anticonvulsant effect of morphine on pentylenetetrazole-induced seizures in mice

Abstract Regarding the proven anticonvulsant effect of Zhumeria majdae essential oil (ZMEO) in previous studies we were prompted to investigate the ZMEO effects on the tolerance to the anticonvulsant effects of morphine and the morphine withdrawal syndrome. Tolerance to the morphine anticonvulsant effect was induced in mice by subcutaneous injection of 2.5 mg/kg of morphine for 4 days. Subsequent doses of ZMEO (20 mg/kg) were used to study the expression and development of morphine tolerance. Clonidine was used as the standard drug to inhibit the morphine withdrawal syndrome symptoms. To study the ZMEO effect on withdrawal syndrome, mice received appropriate morphine values for 4 days and on the fifth day, 60 min before administration of naloxone. The effective dose of ZMEO was determined and the number of jumps, stands and changes in the dry stool weight, as symptoms of withdrawal syndrome were evaluated. The dose of 20 mg/kg of ZMEO decreased the tolerance in development and expression groups significantly. Counting the number of jumping, standing and defecation were assessed 30 min after morphine and 1 h after the vehicle and clonidine. The dose of 40 mg/kg ZMEO decreased all the signs of withdrawal syndrome significantly. ZMEO was analyzed by GC/MS and linalool (53.1%) and camphor (23.8%) were characterized as the main components. The results suggest that ZMEO possesses constituent(s) that have activity against tolerance to the anticonvulsant effects of morphine and the morphine withdrawal symptoms.

Resumo Em relação ao efeito anticonvulsivante comprovado do óleo essencial de Zhumeria majdae (ZMEO) em estudos anteriores, fomos instigados a investigar os efeitos do ZMEO em relação à tolerância aos efeitos anticonvulsivantes da morfina e da síndrome de abstinência de morfina. A tolerância ao efeito anticonvulsivante da morfina foi induzida em camundongos por injeção subcutânea de 2,5 mg/kg de morfina por 4 dias. Doses subsequentes de ZMEO (20 mg/kg) foram utilizadas para estudar a expressão e o desenvolvimento da tolerância à morfina. A clonidina foi usada como droga padrão para inibir os sintomas da síndrome de abstinência da morfina. Para estudar o efeito do ZMEO na síndrome de abstinência, os camundongos receberam valores apropriados de morfina por 4 dias e, no 5º dia, 60 minutos antes da administração de naloxona. A dose efetiva de ZMEO foi determinada, e o número de saltos e de permanência e as alterações no peso das fezes secas, conforme os sintomas da síndrome de abstinência, foram avaliados. A dose de 20 mg/kg de ZMEO diminuiu significativamente a tolerância nos grupos de desenvolvimento e expressão. A contagem do número de saltos, permanência e defecação foi avaliada 30 minutos após a morfina e 60 minutos após o veículo e a clonidina. A dose de 40 mg/kg de ZMEO diminuiu significativamente todos os sinais da síndrome de abstinência. O ZMEO foi analisado por GC/MS, e linalol (53,1%) e cânfora (23,8%) foram caracterizados como os principais componentes. Os resultados sugerem que o ZMEO apresenta constituintes que possuem atividade contra a tolerância aos efeitos anticonvulsivantes da morfina e aos sintomas de abstinência da morfina.

Opioid Withdrawal Symptoms after Conversion to Oral Oxycodone/Naloxone in Advanced Cancer Patients Receiving Strong Opioids / 한국호스피스완화의료학회지

PURPOSE: Oral naloxone is combined with oxycodone to alleviate or prevent opioid-induced constipation in cancer pain patients. However, there is still concern that oral naloxone may precipitate opioid withdrawal symptoms in patients on opioids. We retrospectively investigated clinical characteristics of cancer patients who experienced opioid withdrawal symptoms. METHODS: We reviewed medical records of all patients who were prescribed with oral oxycodone/naloxone at a tertiary cancer center from January 1, 2012 through December 31, 2016. Eligible patients were screened based on demographics, opioid and naloxone dosages, clinical manifestation and pain intensity. RESULTS: Among a total of 1,641 patients, 10 patients were selected. Seven patients were male, and the average age was 68.1 years. The median dose of naloxone that induced withdrawal symptoms was 20 mg. Most common withdrawal symptom was shivering (seven patients) followed by cold sweating (five), and muscle twitching (five). Other symptoms included restlessness, fever, dizziness, and yawning. Pain was exacerbated from the median intensity of numeric rating scale (NRS) 3 to NRS 6. CONCLUSION: Opioid withdrawal symptoms may occur when switching to oral oxycodone/naloxone for cancer patients who have been treated with other strong opioids. A prospective, multicenter study on this issue should be conducted in future.

Pharmacological activation of serotonin 5-HT2C receptor ameliorates naloxone-precipitated withdrawal in morphine-dependent mice / 中国药理学通报

Aim To explore the effect of pharmacolog-ical activation of serotonin 5-HT2C receptor (5-HT2C R) on naloxone-precipitated withdrawal in morphine-de-pendent mice. Method EthoVision Noldus video tracking system was used to record the effect of 5-HT2C R agonist WAY on locomotor activities and behavioral performances in mice.Results Selective 5-HT2C R ag-onist WAY (0.5,0.75 or 1 .0 mg·kg -1 ,i.p.)a-lone did not alter the locomotor activities as determined by distance traveled and velocity (all P values >0.05).Chronic morphine treatment induced depend-ence in mice as demonstrated by increases in distance traveled,velocity and jumping behavior.WAY (0.5, 0.75 or 1 .0 mg·kg -1 ,i.p.)and clonidine (0.2 mg ·kg -1 ,i.p.)significantly ameliorated naloxone-pre-cipitated withdrawal symptoms,including burrowing, jumping,body grooming,rearing,“wet dog”shakes, head shakes,face grooming,penile grooming,scratch (all P values <0.05).Conclusion Pharmacological activation of 5-HT2C R ameliorates naloxone-precipitated withdrawal symptoms in morphine-dependent mice.5-HT2C R may be a novel target to develop therapeutic ap-proach against morphine physical dependence,craving and relapsing.

Antipsychotic discontinuation syndrome following risperidone withdrawal: a case report from rural India.

Risperidone is an atypical antipsychotic agent used primarily to treat schizophrenia. It is a dopamine antagonist with antiserotonergic, antihistaminergic and antiadrenergic properties. Antipsychotic discontinuation symptoms have been described in the literature following abrupt or rapid reduction in the dose. This unusual case demonstrates that sudden withdrawal of even a modest dose of risperidone may cause significant discontinuation symptoms in susceptible individuals. Hence, there is a need for caution while taking a patient off antipsychotic medications in view of the vulnerable subgroup.

Role of spinal neuronal ERK5/CREB signaling pathway in withdrawal responses in morphine-dependent rats / 中华麻醉学杂志

Objective To evaluate the role of spinal neuronal extracellular signal-regulated protein kinases 5/cAMP response element binding protein (ERK5/CREB) signaling pathway in withdrawal responses in morphinedependent rats.Methods Ninety-six adult male Sprague-Dawley rats in which intrathecal catheters were successfully placed,weighing 200-250 g,were randomly divided into 4 groups (n =24 each):normal control group (group A),morphine withdrawal group (group B),dimethyl sulfoxide (DMSO) + morphine withdrawal group (group C) and ERK5 inhibitor BIX02188 + morphine withdrawal group (group D).Morphine dependence (MD) was induced by increasing doses of subcutaneous morphine for 6 days.The initial dose of morphine was 10 mg/kg once a day and was increased by 10 mg/kg once a day from 2nd to 5th days until 50 mg/kg on 6th day in B,C and D groups.Morphine withdrawal response (MW) was induced by intraperitoneal naloxone 4 mg/kg at 4 h after last morphine administration in B,C and D groups.In addition,BIX02188 10 μg and 1％ DMSO 10 μl were injected intrathecally at 1 h before naloxone injection in D and C groups,respectively.MW and morphine withdrawal-induced hyperalgesia were scored.The rats were then sacrificed after hyperalgesia was scored and the spinal cord was removed for determination of CREB and phosphorylated CREB (p-CREB) expression.Results Compared with group A,MW and hyperalgesia scores were significantly increased and the expression of p-CREB was up-regulated in B,C and D groups.Compared with group B,MW and hyperalgesia scores were significantly decreased and the expression of p-CREB was down-regulated in D group,and no significant change was found in group C.Conclusion The spinal neuronal ERK5/CREB signaling pathway is involved in withdrawal responses in morphine-dependent rats.

Roles of spinal N-methyl-D-aspartic acid receptor-extracellular signal-regulated protein kinase 5 signaling pathway in naloxone-induced withdrawal response in morphine-dependent rats / 中华行为医学与脑科学杂志

Objective To investigate the roles of spinal N-methyl-D-aspartic acid receptor-extracellular signal-regulated protein kinases 5 signaling pathway in naloxone-induced withdrawal response in morphine-dependent rats.Methods Ninety-six adult male SD rats weighting 230-250 g were randomly divided into 4 groups:control group,withdrawal group,DMSO group and MK801 group.Rats were subcutaneously injected with morphine.On day 6,rats were injected with naloxone (intraperitoneal) to precipitate morphine withdrawal syndromes.To identify the function of NMDAR-ERK5 signaling pathway in morphine withdrawal,morphine withdrawal-like behavior test and western blot technique were used in this research.The scores of morphine withdrawal symptom,morphine withdrawal-induced allodynia and the activation of ERK5 in spinal cord were observed after intrathecal injection of MK801.Results There was no withdrawal symptoms and withdrawal-induced allodynia in group A after intraperitoneal injection of naloxone.Compared with group A,withdrawal score (45.2±7.3),score of withdrawal-induced allodynia (14.4±3.7) of group B,withdrawal score (44.7±6.2),score of withdrawal-induced allodynia (13.2±2.7) of group C and withdrawal score (28.3±1.6),score of withdrawal-induced allodynia (5.9± 1.1) of group D were significantly increased (P＜ 0.05).Compared with group C,the total withdrawal score (28.3 ± 1.6),score of withdrawal-induced allodynia (5.9± 1.1) of group D were significantly decreased (P＜0.05).Compared with group A,the expression of spinal p-ERK5 of group B (12848±621) and group C (12579±396) were significantly increased (P＜0.05).Compared with group C,the expression of spinal p-ERK5 of group D (5 123±546) was significantly decreased (P＜0.05).Condusion The signaling pathway of spinal N-methyl-D-aspartic acid receptor-extracellular signal-regulated protein kinases 5 contributes to naloxone-induced withdrawal response in morphine-dependent rats.

Acute-Withdrawal Restless Legs Syndrome Following Abrupt Cessation of Short-Term Tramadol

We report a young man who had received tramadol for pain control and experienced an uncomfortable sensation in both legs immediately after tramadol withdrawal that worsened at rest and at night, and which could be relieved only by moving the legs. He suffered from insomnia and paced up and down in his house every night. Readministration of tramadol dramatically resolved his symptoms of restless legs syndrome (RLS), but they reappeared after tramadol withdrawal. Tramadol was therefore replaced with ropinirole, which was discontinued after several weeks, and there was no recurrence of his RLS symptoms. This patient appeared to have developed tramadol-withdrawal-induced RLS, and this case report emphasizes the importance of monitoring for withdrawal-type symptoms like RLS when tramadol intake is being stopped.

Management of benzodiazepine dependence and toxicity.

The key target of this review is to compare the efficacies of the different adjuncts and methods used in the management of benzodiazepine dependence (tolerance and withdrawal) and poisoning. A systemic review of randomized controlled trials was carried out to determine which method of adjuvant therapy can be best used to overcome the withdrawal symptoms exhibited during benzodiazepine discontinuation. In addition, different tapering methods employed have also been presented in this review. Zolpidem in combination with cognitive behavioural therapy with a parallel gradual taper after conversion to long half-life Benzodiazepine seems to be a promising method among the several analysed. Finally the efficacies of the two available methods to combat benzodiazepine toxicity, namely flumazenil and naloxone have been discussed and compared.

Effect of inhibition of spinal extracellular signal-regulated protein kinase 5 on morphine withdrawal in rats with morphine dependence / 中华行为医学与脑科学杂志

Objective To investigate the roles of spinal extracellular signal-regulated protein kinases 5 (ERK5) on morphine withdrawal in rats.Methods Ninety-six male and adult SD rats weighting 230-250 g were randomly divided into saline-naloxone-DMSO group (group A),saline-naloxone-BIX02188 group (group B),morphine-naloxone-DMSO group (group C) and morphine-naloxone-BIX02188 group (group D).To set up morphine dependent model,rats were subcutaneously injected with morphine in the increasing dosage method.On day 6,4 h after the injection of morphine,rats were injected with naloxone (intraperitoneal) to precipitate morphine withdrawal syndrome.The scores of morphine withdrawal symptom and morphine withdrawal-induced allodynia were observed after intrathecal injection of ERK5 inhibitor BIX02188.Result There were not withdrawal symptoms and withdrawal-induced allodynia in group A and B after intraperitoneal injection of naloxone.Compared with group A,teeth chatting (7.5± 1.1),wet dog shacks (4.6± 0.7),jump (5.3± 0.7),abnormal position (8.9± 1.9),diarrhea (7.1 ± 1.6),salivation (2.8±0.6),weight loss (7.9±0.9),total withdrawal score (44.8±5.9),score of withdrawalinduced allodynia (14.6±2.4) of group C and teeth chatting (3.1±0.5),wet dog shacks (1.5±0.4),jump (2.2± 0.5),abnormal position (7.9± 1.6),diarrhea (1.8±0.5),salivation (2.8±0.9),weight loss (3.7±0.6),total withdrawal score (23.1± 1.3) and score of withdrawal-induced allodynia (3.5± 1.1) of group D were significantly increased (P＜0.05).Compared with group C,teeth chatting (3.1±0.5),wet dog shacks (1.5±0.4),jump (2.2±0.5),diarrhea (1.8±0.5),weigbt loss (3.7±0.6) and total withdirawal score (23.1±1.3),score of withdrawal-induced allodynia (3.5±1.1) of group D were significantly decreased (P＜0.05).But there was not significant change in abnoral position (7.9±1.6) and salivation (2.8±0.9).Conclusion Inhibition of the activation of spinal cord ERK5 can significantly alleviate withdrawal symptoms of morphine dependent rats by intrathecal injection BIX02188.

Role of extracellular signal-regulated protein kinase 5 in spinal cord in withdrawal responses in morphine-dependent rats / 中华麻醉学杂志

Objective To evaluate the role of extracellular signal-regulated protein kinase 5 (ERK5) in the spinal cord in withdrawal responses in morphine-dependent rats.Methods Ninety-six adult male SpragueDawley rats in which intrathecal catheters were successfully placed,weighing 200-250 g,were randomly divided into 4 groups (n =24 each) using a random number table:normal saline group (group A),withdrawal group (group B),dimethyl sulfoxide (DMSO) group (group C) and ERK5 inhibitor BIX02188 group (group D).Morphine dependence (MD) was induced by increasing doses of subcutaneous morphine for 6 days.The initial dose of morphine was 10 mg/kg once a day and was increased by 10 mg/kg once a day from the 2nd to 5th days until 50 mg/kg on the 6th day in B,C and D groups.Morphine withdrawal response (MW) was induced by intraperitoneal naloxone 4 mg/kg at 4 h after last morphine administration in B,C and D groups.In addition,BIX02188 and 1％ DMSO 10 μl were injected intrathecally at 1 h before naloxone injection in D and C groups,respectively.MW and morphine withdrawal-induced hypemlgesia were scored.The rats were then sacrificed after hyperalgesia was scored and the spinal cord was removed for determination of ERK5 and phosphorylated ERK5 (p-ERK5) expression.Results Compared with group A,MW and hyperalgesia scores were significantly increased and the expression of pERK5 was up-regulated in B,C and D groups (P ＜ 0.05).Compared with group B,MW and hyperalgesia scores were significantly decreased and the expression of p-ERK5 was down-regulated in D group (P ＜ 0.05),and no significant change was found in group C (P ＞ 0.05).Conclusion ERK5 in the spinal cord is involved in withdrawal responses in morphine-dependent rats.

Effect of Salvia mildorrhiza extracts on formation of morphine physical dependence in mice and its possible mechanism / 中草药

Objective: To observe the action of Salvia miltiorrhiza extracts (SmE2, liposoluble constituents) on the formation of physical dependence induced by morphine in mice and the effects of SmE2 on the production of cyclic adenosine monophosphate (cAMP) and nitric oxide (NO) in brain of morphine-dependent mice. Methods: Morphine-dependent mice model was established by sc injection of morphine at a gradual increasing dosage. The effect of SmE2 on the withdrawal symptoms induced by Naloxone in morphine-dependent mice was observed. cAMP and NO content in brain were determined through radioimmunoassay and nitrate reductase, respectively. Results: SmE2 (80 mg/kg) could remarkably reduce the withdrawal symptoms in morphine-dependent mice. The cAMP concentration in brain showed no obvious change in morphine-dependent mice treated with SmE2, but NO content in brain could significantly be reduced. Conclusion: SmE2 has effect on relieving the withdrawal symptoms in morphine-dependent mice with down-regulation of NO content in brain as possible mechanism.

Changes in Blood Superoxide Dismutase Activities after Alcohol Withdrawal

OBJECTIVES: The aims of this study were to evaluate changes in plasma superoxide dismutase(SOD) activities in alcohol depedence, to fine out variables to influence on the SOD activities, and finally to identify the correlation of SOD activities with the alcohol-associated cognitive disorders. METHODS: For 24 male alcoholics and 21 healthy male controls, plasma SOD activities were measured by spectrophotometry on 1-2 wks after alcohol withdrawal. Structured interviews and laboratory tests were also performed. RESULTS: 1) Upon comparing SOD activities between controls and alcoholics, the SOD activities were significantly(p<0.01) lower in alcoholics(0.308+/-0.140 units/mL) than in healthy controls(0.313+/-0.086 units/mL). 2) Upon comparing SOD activities according to the presence of alcohol-related cognitive disorders, the SOD activities were significantly(p<0.05) lower in alcoholics with cognitive disorders(0.247+/-0.049 units/mL) than in alcoholics without cognitive disorders(0.317+/-0.148 units/mL). 3) Upon comparing SOD activities according to the presence of alcoholic polyneuropathy or alcohol withdrawal seizure, the SOD activities showed no significant differences between alcoholics with polyneuropathy or epilepsy and those without. 4) Upon analyzing variables influencing on the SOD activities in alcoholics, the SOD activities had the negative correlation with hemoglobin(gamma=-0.433) and severity of alcohol withdrawal symptoms(gamma=-0.375). 5) Upon comparing variables according to the presence of alcohol-related cognitive disorders, the occurrence of alcoholic polyneuropathy(p<0.05) and blood phosphorus concentrations(p<0.01) were significantly higher in alcoholics with cognitive disorders than those without. 6) Upon analyzing an association between SOD activities and variables in alcoholics with cognitive disorders, the SOD activities were positively correlated with the onset age(gamma=0.995), and negatively correlated with the severity of alcohol withdrawal symptoms(gamma=-0.996). CONCLUSIONS: Lower SOD activities in alcohol dependence suggested alcohol-associated cognitive disorders and alcohol withdrawal symptoms might be caused by oxidative stress.

Efficacy of Huoxiangzhengqi Oral Liquid and Tablet of Radix et Caulis Acanthopanacis Senticosi on withdrawal symptoms from heroin / 中成药

AIM:To observe the therapeutic efficacy of Huoxiangzhengqi Oral Liquid (Herba Agastaches seu Pogostemi, Radix Angelicae Dahuricae, Rhizoma Atractylodis, Rhizoma Pinelliae, Pericarpium Citri Reticulatae, Pericarpium Arecae) and Tablet of Radix et Caulis Acanthopanacis Senticosi on the withdrawal symptoms from heroin. METHODS: 143 cases were randomly divided into three groups, namely control group (n=44), treating group A (n=48) and B (n=51). They were detoxified by using Lofexidine Hydrochloride Tablet (LFX) for 12d, and then, the control group took an imitate preparation, the treating group A took Huoxiangzhengqi Oral Liquid and Tablet of Radix et Caulis Acanthopanacis Senticosi for 60d, But group B took Huoxiangzhengqi Oral Liquid and Tablet of Radix et Caulis Acanthopanacis Senticosi from the time when detoxification began. And then, 10d after the two treating groups stopped taking Huoxiangzhengqi Oral Liquid and Tablet of Radix et Caulis Acanthopanacis Senticosi, the protracted abstinent syndromes of the three group were observed and scored for 7d. One year later, the drug re abusing case of the three groups were investigated through urinoscopy. RESULTS: The scores of the protracted abstinent symptoms of the three groups were distinctively different. The scores of the treating group were lower than those of the treating group A ( P

Effect of Sildenafil on Morphine Withdrawal Symptoms in Mice / 中国心理卫生杂志

Objective: To observe the effect of phophodiesterase 5 (PDE5) inhibitor, sildenafil on morphine withdrawal symptoms in mice. Method: A physical morphine dependent model in mice was established by subcutaneous injection of morphine in gradually increasing doses. After interperitoneal injection of naloxone (0.2mg/kg), withdrawal symptoms including jumping in 15 min, jumping latent period and weight loss were scored to evaluate the response intensity of morphine withdrawal. The effect of sildenafil (15mg/kg, 30mg/kg and 60mg/kg) was observed. Using nitrate reductase method to detect NO (nitric oxide) content in the blood and brain of mice. Result: Morphine withdrawal symptoms were aggravated by 3 different dosage of sildenafil and assumed good dose-dependent manner. NO content in blood increased after 30mg/kg sildenafil, which had no effect on NO content in brain of mice. Conclusion: Morphine withdrawal symptoms can be aggravated by sildenafil, which has also influence on blood content of NO, but has no influence on NO content in brain.