Role of Xingnaojing combined with naloxone in treating intracerebral haemorrhage: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Xingnaojing injection (XNJ) sharpen the mind and induce consciousness and are widely used in acute phases of intracerebral hemorrhage (ICH). Naloxone hydrochloride injection (NX) performs equally well and replace the effects of morphine-like substances to promote conscious awareness. The applications of XNJ combined with NX for ICH show some advantages compared with NX applied individually. The aim of this systematic review is to evaluate the effectiveness and safety of XNJ combined with NX for ICH. METHODS: Comprehensive searches were conducted in 8 medical databases (PubMed, Cochrane Library, Web of Science, Embase, CNKI, VIP, CBM and Wanfang database) from inceptions to October 2017 for randomized controlled trials (RCTs) that compared the applications of XNJ and NX with NX applied individually in ICH. Literature screening, assessing risk of bias and data extraction were conducted by 2 reviewers independently. According to the Cochrane Collaboration's RevMan5.3 software to perform the data analysis. RESULTS: 32 RCTs (3068 cases) were selected and the quality of studies were low. All trials compared XNJ and NX with NX applied individually. The overall meta-analysis results showed that XNJ combined with NX have significant effect on clinical efficacy (OR 3.78, 95% CI: 3.03-4.73; P < .00001), GCS score (MD 3.86, 95% CI: 3.46-4.25; P < .00001), coma duration (MD -5.59, 95% CI: -6.96 to -4.22; P < .00001), NIHSS score (MD -6.24, 95% CI: -8.05 to -4.42; P < .00001), Barthel Index score (MD 14.12, 95% CI: 6.7-21.54; P < .0002), cerebral hematoma volume (MD -6.05, 95% CI: -6.85 to -5.24; P < .00001) than NX applied individually. Adverse events reported in 4 studies and included mild discomfort symptoms. CONCLUSION: The effectiveness and safety of XNJ combined with NX for ICH cannot be determined due to the low quality of literature, publication bias and heterogeneity. More rigorous RCTs are necessary to verify the role of XNJ combined with NX in the treatment of ICH.

Experimental Research Showing the Reduction of Naloxone-Place Aversion by Oral Zinc Administration in Rats.

Previous studies showed the attenuation of both morphine-dependence and morphine-place preference by zinc. Conditioned place preference and aversion are experimental models frequently used to test the reward-stimulating, respectively the aversive effects induced by different stimuli or substances. Addictive substances usually induce place preference (exhibit reward-stimulating properties), while their antagonists determine place-avoidance (aversion). The present study aimed to assess the effect determined by zinc sulphate oral administration (2 and 4 mg/kg/day, 14 days, prior to habituation) on the place aversion induced by two naloxone doses (1.5 and 2.5 mg/kg/administration). The results show a robust, dose-dependent reduction of the aversion determined by both naloxone doses (the aversion induced by 1.5 mg/kg naloxone was reduced with 15%-the lower zinc dose and with 24%-the higher zinc dose; the aversion induced by 2.5 mg/kg naloxone was reduced with 16%-the lower zinc dose and with 29%-the higher zinc dose). This represents a new proof of the interactions between zinc and opioidergic system and a further argument for dietary zinc supplementation in patients on opioids for cancer-related chronic pain.

Yiguanjian cataplasm attenuates opioid dependence in a mouse model of naloxone-induced opioid withdrawal syndrome.

OBJECTIVE: To investigate the effect of Yiguanjian (YGJ) cataplasm on the development of opioid dependence in a mouse model of naloxone-induced opioid withdrawal syndrome. METHODS: One hundred Swiss albino mice, of equal male to female ratio, were randomly and equally divided into 10 groups. A portion (3 cm2) of the backside hair of the mice was removed 1 day prior to the experiment. Morphine (5 mg/kg) was intraperitoneally administered twice daily for 5 days. YGJ cataplasm was prepared and pasted on the bare region of the mice immediately before morphine administration on day 3 and subsequently removed at the end day 5. On day 6, naloxone (8 mg/kg) was intraperitoneally injected to precipitate opioid withdrawal syndrome. Behavioral observation was performed in two 30-min phases immediately after naloxone injection. RESULTS: The YGJ cataplasm significantly and dose-dependently attenuated morphine-naloxone- induced experimental opioid withdrawal, in terms of withdrawal severity score and the frequencies of jumping, rearing, forepaw licking, and circling behaviors. However, YGJ cataplasm treatment did not alter the acute analgesic effect of morphine. CONCLUSION: YGJ cataplasm could attenuate opioid dependence and its associated withdrawal symptoms. Therefore, YGJ cataplasm could serve as a potential therapy for opioid addiction in the future.

Hospitalist management of vaso-occlusive pain crisis in patients with sickle cell disease using a pathway of care.

BACKGROUND: Patients with sickle cell disease (SCD) suffer from intermittent vaso-occlusive pain crises (VOCs). These crises lead to frequent hospitalizations, significant morbidity, and increased mortality risk. Care pathways can enhance efficiency and quality of care. Our study sought to evaluate the development and implementation of a care pathway for patients with SCD experiencing VOCs. METHODS: The University of North Carolina (UNC) Comprehensive Sickle Cell Program provides all levels of care for a large population of patients with sickle cell anemia. All patients admitted to UNC Hospitals with SCD VOCs from January 2009 through June 2011 were evaluated. During this time period, we also assessed sequential prospective cohorts during progressive phases of developing and implementing a quality improvement and pathway of care program for this patient population in our study. The developed pathway entailed geographic localization for VOC patients, a single group of faculty physicians caring for these patients, and early use of patient-controlled analgesia (PCA) to achieve pain control. Physicians from the UNC Hospital Medicine Program were responsible for the initiatives. Cohorts were compared to a baseline historical control. Outcomes of interest included patient length of stay (LOS) in the hospital, 30-day readmission rate, need for transfusion, incidence of acute chest syndrome, use of naloxone, and use of PCA. RESULTS: Compared with an historical baseline cohort, the development and implementation of a VOC care pathway for patients with SCD led to reduction in average hospital LOS by 1.44 days (P < 0.05) and an increase in use of PCAs (P < 0.05). Patient readmission rates, number of transfusions, incidence of acute chest syndrome, and use of naloxone did not significantly change. CONCLUSIONS: Hospitalist-led management of patients with SCD VOCs using a care pathway that emphasizes early, aggressive PCA-based pain control is associated with reduced hospital LOS. The LOS reduction seen in our study is clinically meaningful. Notably, other measures of patient outcomes and quality of care metrics did not change significantly, and some trended towards improvement.

Use of conventional, complementary, and alternative treatments for pain among individuals seeking primary care treatment with buprenorphine-naloxone.

UNLABELLED: Previous studies have not examined patterns of pain treatment use among patients seeking office-based buprenorphine-naloxone treatment (BNT) for opioid dependence. OBJECTIVES: To examine, among individuals with pain seeking BNT for opioid dependence, the use of pain treatment modalities, perceived efficacy of prior pain treatment, and interest in pursuing pain treatment while in BNT. METHODS: A total of 244 patients seeking office-based BNT for opioid dependence completed measures of demographics, pain status (ie, "chronic pain (CP)" [pain lasting at least 3 months] vs "some pain (SP)" [pain in the past week not meeting the duration criteria for chronic pain]), pain treatment use, perceived efficacy of prior pain treatment, and interest in receiving pain treatment while in BNT. RESULTS: In comparison with the SP group (N = 87), the CP group (N = 88) was more likely to report past-week medical use of opioid medication (adjusted odds ratio [AOR] = 3.2; 95% CI, 1.2-8.4), lifetime medical use of nonopioid prescribed medication (AOR = 2.2; 95% CI, 1.1-4.7), and lifetime use of prayer (AOR = 2.8; 95% CI, 1.2-6.5) and was less likely to report lifetime use of yoga (AOR = 0.2; 95% CI, 0.1-0.7) to treat pain. Although the 2 pain groups did not differ on levels of perceived efficacy of prior lifetime pain treatments, in comparison with the SP group, the CP group was more likely to report interest in receiving pain treatment while in BNT (P < 0.001). CONCLUSIONS: Individuals with pain seeking BNT for opioid dependence report a wide range of conventional, complementary, and alternative pain-related treatments and are interested (especially those with CP) in receiving pain management services along with BNT.

Effect of acupuncture on naloxone-precipitated withdrawal syndrome in morphine-experienced rats: the mediation of GABA receptors.

Repeated morphine administration increases extracellular dopamine levels in the nucleus accumbens, which results in behavioral sensitization that can be suppressed by acupuncture at Shenmen (HT7) points. The present study was conducted to investigate the effects of acupuncture at HT7 on morphine withdrawal syndrome as well as to explore the role of GABA receptors in mediating the effects of HT7 acupuncture. We induced morphine withdrawal by injecting naloxone to rats that self-administer morphine and evaluated the effects of acupuncture and/or GABA receptor antagonists on their withdrawal symptoms. Acupuncture at HT7, but not at the control point LI5, significantly decreased symptoms of morphine withdrawal. HT7 inhibition of the withdrawal syndrome was blocked by pretreatment with either the GABA(A) receptor antagonist bicuculline or the GABA(B) antagonist SCH 50911. These findings suggest that the effects of acupuncture on suppression of morphine withdrawal syndrome are mediated, at least in part, through GABA receptors.

Predictors of buprenorphine-naloxone dosing in a 12-week treatment trial for opioid-dependent youth: secondary analyses from a NIDA Clinical Trials Network study.

INTRODUCTION: The present investigation examines baseline patient characteristics to predict dosing of buprenorphine-naloxone, a promising treatment for opioid addiction in youths. METHODS: This study of 69 opioid-dependent youths is a secondary analysis of data collected during a National Institute on Drug Abuse (NIDA) Clinical Trials Network study. Outpatients aged 15-21 were randomized to a 12-week buprenorphine-naloxone dosing condition (including 4 weeks of taper). Predictors of dosing included sociodemographic characteristics (gender, race, age, and education), substance use (alcohol, cannabis, cocaine, and nicotine use), and clinical characteristics (pain and withdrawal severity). RESULTS: Most (75.4%) reported having either "some" (n=40, 58.0%) or "extreme" (n=12, 17.4%) pain on enrollment. Maximum daily dose of buprenorphine-naloxone (19.7 mg) received by patients reporting "extreme" pain at baseline was significantly higher than the dose received by patients reporting "some" pain (15.0mg) and those without pain (12.8 mg). In the adjusted analysis, only severity of pain and withdrawal significantly predicted dose. During the dosing period, there were no significant differences in opioid use, as measured by urinalysis, by level of pain. CONCLUSION: These data suggest that the presence of pain predicts buprenorphine-naloxone dose levels in opioid-dependent youth, and that patients with pain have comparable opioid use outcomes to those without pain, but require higher buprenorphine-naloxone doses.

A prolonged protein kinase C-mediated, opioid-related antinociceptive effect of st John's Wort in mice.

UNLABELLED: The antinociceptive profile of St. John's Wort (SJW) was investigated in mice in a condition of acute thermal and chemical pain, together with the mechanism that might underlie this effect. A dried extract of SJW induced a prolonged antinociception that persisted for 120 minutes after administration. The thermal antinociception was prevented by naloxone and by the protein kinase C (PKC) activator PMA, whereas the chemical antinociception was prevented by PMA, remaining naloxone insensitive. A chloroform (CHL) and a methanol (MET) fraction, obtained to investigate the involvement of the SJW main components, hyperforin and hypericin/flavonoid, respectively, increased pain threshold with a time course comparable to the dried extract. The CHL antinociception was prevented by naloxone, whereas the MET antinociception was antagonized by PMA. Purified hyperforin and hypericin showed an antinociceptive efficacy comparable to CHL and MET, respectively. Conversely, flavonoids were devoid of any effect. The administration of yohimbine and atropine did not modify SJW, CHL and MET antinociception. These results indicate that both CHL and MET fractions mediate the SJW-induced antinociception. In particular, the presence of hypericin was fundamental to induce both thermal and chemical antinociception through the inhibition of the PKC activity, whereas hyperforin selectively produced a thermal opioid antinociception. PERSPECTIVE: This article presents evidence of a persistent thermal and chemical antinociception of SJW that is mainly mediated by PKC-inhibiting mechanisms. These findings identify important targets for a longer-acting activation of endogenous pain systems and should potentially help clinicians who seek safe, tolerable, and prolonged treatments for pain relief.

Effects of aqueous, methanolic and chloroform extracts of rhizome and aerial parts of Valeriana officinalis L. on naloxone-induced jumping in morphine-dependent mice.

In the present study, the effects of rhizomes and aerial parts extracts of Valeriana officinalis L. on morphine dependence in mice have been investigated. Animals were treated subcutaneously with morphine (50, 50 and 75 mg/kg) three times daily (10 am, 1 pm and 4 pm) for 3 days, and a last dose of morphine (50 mg/kg) was administered on the fourth day. Withdrawal syndrome (jumping) was precipitated by naloxone (5 mg/kg) which was administered intraperitoneally 2 hours after the last dose of morphine. To study the effects of the aqueous, methanolic and chloroform extracts of both aerial parts and rhizome of the V. officinalis L. on naloxone-induced jumping in morphine-dependent animals, 10 injections of morphine (three administrations each day) for dependence and a dose of 5 mg/kg of naloxone for withdrawal induction were employed. Intraperitoneal injection of different doses (1, 5, 25 and 50 mg/kg) of aqueous, methanolic and chloroform extracts of the rhizome of V. officinalis L. 60 minutes before naloxone injection decreased the jumping response dose-dependently. Pre-treatment of animals with different doses (1, 5, 25, 50 and 100 mg/kg) of aqueous and methanolic extracts of aerial parts of V. officinalis L. 60 minutes before naloxone injection caused a significant decrease on naloxone-induced jumping. The chloroform extract of the aerial parts of V. officinalis L. did not show any significant changes on jumping response in morphine-dependent animals. It is concluded that the extracts of V. officinalis L. could affect morphine withdrawal syndrome via possible interactions with inhibitory neurotransmitters in nervous system.

Inpatient initiation of buprenorphine maintenance vs. detoxification: can retention of opioid-dependent patients in outpatient counseling be improved?

Buprenorphine-naloxone is an office-based opioid agonist released in 2003 in the United States for the maintenance of heroin- and other opioid-dependent patients. Concern has been raised that the medication will distract or otherwise inhibit patients from participating in a holistic recovery program or abstinence-based counseling. Using a retrospective chart review, the first thirty opioid-dependent patients induced on buprenorphine maintenance therapy in an inpatient detoxification unit were compared to thirty age- and gender-matched patients who underwent detoxification (with a tramadol taper) and referral to intensive outpatient treatment. The clinical outcomes were a comparison of completion rates for an intensive outpatient program (IOP) and retention in treatment after twelve weeks of aftercare therapy. Patients induced on buprenorphine maintenance over three days had similar relief of withdrawal symptoms to patients detoxified from opioids over five days with tramadol. Patients maintained on buprenorphine had a markedly increased initiation of IOP and remained in outpatient treatment longer than patients who were detoxified (8.5 wks vs. 0.4 wks, p < 0.001). This study indicates that induction and maintenance on buprenorphine may be more effective than detoxification for engaging and retaining patients in abstinence-based comprehensive outpatient addiction treatment.

Cross-generalization of an EtOH "hangover" cue to endogenously and exogenously induced stimuli.

Twenty male Sprague-Dawley rats were trained in a two-choice food-reinforced drug discrimination task (10 min sessions) using the state-dependent interoceptive stimulus attributes of ethanol's (EtOH) delayed or rebound effects (EDE) versus "normal" basal homeostasis. Cross-generalization tests were conducted with 0.18 mg/kg naloxone injected after three days of three injections per day of either SAL or 10 mg/kg morphine. Naloxone failed to generalize to the EDE-state after chronic saline; however, the precipitated morphine withdrawal state produced complete generalization to the EDE training cue. Daily tests were conducted after 8 h photoperiod phase-shifts. An 8 h phase-advance, equivalent to a west-to-east intercontinental night-time flight in humans, produced a biphasic, graded, increase in EDE-appropriate responding, which peaked on the second day after the phase-advance and recovered by the fourth day. The 8 h phase-delays failed to engender significant EDE-appropriate responding. These data provide evidence for the subjective similarity between EtOH hangover, opiate withdrawal states, and the physiological disruption induced by circadian phase-advances.

Reversible, titrated deep sedation for major office surgery.

We have operated upon 446 consecutive patients in the office, using the controlled titrated method of sedation which we have described. We believe the results are superior to the methods in more common use. A major factor in choosing a narcotic as our one basic drug was the availability of a safe, swift, and effective antidote to it.