dezocine and Pain

Dezocine, a synthetic opioid, introduced in 1970s as an analgesic, was redeveloped for relieving moderate to severe pain by Yangtze River Pharmaceutical Group in China in 2009. To date, dezocine occupies 45% of China's opioid analgesic market. Along with dezocine being a dominated painkiller, a certain amount of research was conducted to elucidate dezocine's action. In this review we summarize the current knowledge on the receptor, preclinical and clinical pharmacology of dezocine. Briefly, preclinical data show that dezocine is effective under varying pain conditions, particularly chronic neuropathic pain and cancer pain, through activation of opioid receptors, and inhibition of norepinephrine reuptake. Clinical data establish the effectiveness of dezocine either as a primary analgesic for postoperative pain management or a supplement for balanced analgesia. The receptor profile of dezocine is different from known pure μ agonists, and allows it to be used in combination with other opioids for additivity in efficacy or lower incidence of adverse effects.

Topics: Analgesics; Analgesics, Opioid; Bridged Bicyclo Compounds, Heterocyclic; Humans; Pain; Tetrahydronaphthalenes

The association between the efficacy and safety of dezocine injection and morphine injection for persistence of pain in patients with cancer had yielded controversial results. Therefore, we conduct a meta-analysis of existing observational published studies to assess the relationship between them among Chinese. We conducted a comprehensive research from the databases of PubMed, Web of Science, and Wan Fang Med Online for the related studies up to October 2016. Summary odds ratio (OR) with 95% confidence interval (95% CI) were calculated with the random effects model. Nine published studies comprising 333 dezocine injection patients and 321 morphine injection patients were included in this meta-analysis. Our results suggested that there was no statistical significance between dezocine injection and morphine injection at the case number of effective pain relief (EPR) [OR = 0.97, 95% CI (0.77-1.22),

Topics: Asian People; Bridged Bicyclo Compounds, Heterocyclic; China; Female; Humans; Male; Morphine; Neoplasms; Pain; Tetrahydronaphthalenes

The current experiment was carried out to explore the effects of dezocine combined with ropivacaine infiltration anesthesia on the anesthesia recovery time and pain factors of patients with open hepatectomy. A prospective randomized controlled method was used to select 92 patients with open liver cancer resection in our hospital from August 2017 to November 2019. The patients were divided into a study group (n=46) and a control group (n=46) using a computer-generated random number table. Both groups underwent general anesthesia, based on this, the study group was treated with ropivacaine infiltration anesthesia 10 minutes before skin incision, and dezocine was given intravenously 0.5 h before surgery, the control group was anesthetized with ropivacaine 10 minutes before the incision, and was given a saline injection 0.5 h before the operation. Compared the recovery of anesthesia (recovery time of spontaneous breathing, time to open eyes, time to extubation), the incidence of adverse reactions, and cellular immune function indicators (peripheral blood CD4+, CD4+/CD8+, NK cell levels), stress response indicators [serum blood glucose (Glu), norepinephrine (NE), adrenaline (E)], pain factors [serum dopamine (DA), neuropeptide Y (NPY), substance P (SP)] before induction of anesthesia (T0), completion of surgery (T1), 12 hours after surgery (T2), and 24 hours after surgery (T3) between the two groups, and the degree of pain (VAS score) at T2 and T3 were compared between the two groups. The levels of CD4+, CD4+/CD8+, and NK cells in peripheral blood at T1, T2, and T3 in the study group were higher than those in the control group (P<0.05); serum Glu, NE, and E levels in the study group at T1, T2, and T3 were lower than those in the control group (P<0.05); serum DA, NPY, and SP levels in the study group at T1, T2, and T3 were lower than those in the control group (P<0.05); the VAS scores of the study group at T2 and T3 were lower than those of the control group (P<0.05); the time of spontaneous breathing recovery, eyes opening and extubation in the study group were shorter than those in the control group (P<0.05); the incidence of restlessness (4.35%), transient hypertension (6.52%), and cough (2.17%) in the study group were lower than those in the control group (P<0.05). Dezocine and ropivacaine infiltration anesthesia can significantly shorten the recovery time of anesthesia and inhibit pain factor secretion in patients with open hepatectomy an

Topics: Aged; Anesthesia Recovery Period; Anesthesia, General; Bridged Bicyclo Compounds, Heterocyclic; Female; Humans; Liver; Male; Middle Aged; Pain; Pain Measurement; Ropivacaine; Stress, Physiological; Tetrahydronaphthalenes

The best methods for inducing analgesia and sedation for gastroscopy are still debated but finding an adequate regimen of sedation/analgesia is important. Stimulation of the larynx under sedation can cause reflex responses. Propofol with opioids has been recommended for gastroscopy sedation but the effects on cough reflex suppression remain unclear. This trial will evaluate the effects of propofol combined with small doses of dezocine, oxycodone, sufentanil or fentanyl for gastroscopy. We hypothesise that better performance may be obtained with a combination of propofol and oxycodone. We will observe the incidence and degree of reflex coughing and gagging under sedation when using propofol combined with one of the above drugs or propofol alone.. This will be a prospective, randomised, double-blind, controlled trial. ASA I-II level patients aged 18-65 years and scheduled for gastroscopy will be included. It is planned that 500 subjects will be randomised to intravenously receive 2-2.2 mg/kg propofol plus 0.5-0.8 μg/kg fentanyl (fentanyl group), 2-2.2 mg/kg propofol plus 0.05-0.08 μg/kg sufentanil (sufentanil group), 2-2.2 mg/kg propofol plus 0.04-0.05 mg/kg dezocine (dezocine group), 2-2.2 mg/kg propofol plus 0.04-0.05 mg/kg oxycodone (oxycodone group), or 2.4-3 mg/kg propofol plus 2-2.5 mL saline (control group) for sedation. The primary endpoint is the incidence and degree of reflex coughing and gagging. The secondary endpoints include the occurrence of discomfort or side effects, the use of jaw thrust, assisted ventilation or additional propofol, recovery time, duration of procedure and Steward score.. This study has been approved by the Institutional Ethics Committee for Clinical Research of Zhongda Hospital, Affiliated to Southeast University (No. 2015ZDSYLL033.0). The results of the trial will be published in an international peer-reviewed journal.. This study has been registered with the Chinese Clinical Trial Register (No. ChiCTR-ICR-15006952).. At the time of manuscript submission, the study was in the recruitment phase.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Antitussive Agents; Bridged Bicyclo Compounds, Heterocyclic; Conscious Sedation; Cough; Double-Blind Method; Drug Therapy, Combination; Female; Fentanyl; Gagging; Gastroscopy; Humans; Hypnotics and Sedatives; Male; Middle Aged; Pain; Propofol; Prospective Studies; Reflex; Research Design; Tetrahydronaphthalenes; Young Adult

The pharmacokinetic properties of dezocine were examined in 15 patients with acute or chronic pain. In 3 groups of 5 patients each, serum levels were determined at various intervals after single intravenous doses of 5, 10, and 20 mg. After these single doses, dezocine was very rapidly distributed (mean t1/2 alpha less than 2 minutes), and then rather rapidly eliminated (mean t1/2 beta about 4 hours); the apparent volume of distribution was large (mean Vz beta about 6 L/kg) as was the total clearance (mean CL about 1.5 L/h/kg). In 2 groups of 5 patients each, serum levels were determined after the first and third of 3 intravenous doses of 5 or 20 mg given at 3-hour intervals. The pharmacokinetic parameters after these multiple doses were consistent with those after the single doses. Although some observations were suggestive, there was no unequivocal evidence that the pharmacokinetics were dose-related. In 7 serum samples containing dezocine at concentrations ranging from 12.8 to 522 ng/mL, the mean (+/- SE) proportion of dezocine bound to protein was 91.6 +/- 0.8%.

Topics: Acute Disease; Analgesics, Opioid; Bridged Bicyclo Compounds, Heterocyclic; Chronic Disease; Cycloparaffins; Drug Administration Schedule; Female; Half-Life; Humans; Injections, Intravenous; Male; Metabolic Clearance Rate; Pain; Tetrahydronaphthalenes

Adult patients who had arthroscopic surgery under general anesthesia and requested postoperative pain relief were randomized to receive treatment in a double-blind protocol with 5 mg of intravenous dezocine (20 patients), morphine (22 patients), nalbuphine (18 patients), or saline (24 patients). At 10-min intervals, starting with the first dose of analgesic, patients could choose up to three additional doses of the primary treatment, or choose an alternative analgesic if the primary drug was unsatisfactory. One to four doses of morphine were given as the alternate treatment if the initial treatment was dezocine or nalbuphine, and one to four doses of dezocine were given if the initial treatment was saline or morphine. The proportion of patients treated successfully by the initial treatments (i.e., not requesting alternate treatment), with P value for difference from placebo treatment, were saline 25%, nalbuphine 33% (P = 0.048), morphine 54% (P = 0.04), and dezocine 75% (P = 0.003). Dezocine and morphine are more efficacious than nalbuphine in the management of early postoperative pain. As an alternate analgesic in this study, dezocine required fewer doses to achieve patient satisfaction and was thus more efficacious than morphine. The incidence of treatment-related, adverse effects was different from that of saline or other treatments only for nalbuphine-related pain or burning on injection and dezocine-related facial itching. With respect to analgesic actions and side effects, dezocine seems more like morphine than nalbuphine.

Topics: Adult; Aged; Ambulatory Surgical Procedures; Analgesics; Bridged Bicyclo Compounds, Heterocyclic; Cycloparaffins; Female; Humans; Male; Middle Aged; Morphine; Nalbuphine; Pain; Postoperative Period; Prospective Studies; Tetrahydronaphthalenes

Sixty hospitalized subjects with chronic moderate to severe pain as a result of advanced cancer were enrolled in a randomized, parallel, double-blind trial comparing single doses and multiple doses of intramuscular dezocine (10 mg) with butorphanol (2 mg) and placebo. During the initial 6-hour efficacy evaluation, analgesia was measured using verbal and visual scriptors and vital signs, and acute toxicity information was recorded. Subjects with initial pain relief entered the 7-day multidose portion of the trial, and efficacy and toxicity data were recorded daily. After the initial dose the peak analgesia of the active agents was similar, but the duration of analgesia was longer with dezocine. After multiple doses, dezocine was superior to butorphanol in terms of length of treatment. Dezocine had less toxicity than had butorphanol after both single and repeated doses, further suggesting that dezocine may be beneficial in managing chronic cancer pain. The described study design is unique in that it compares the analgesic efficacy and toxicity of several analgesics with placebo after both single and multiple doses in the same subject. This method may prove to be an alternative pain model to evaluate chronic cancer pain.

Topics: Adult; Aged; Aged, 80 and over; Analgesics; Bridged Bicyclo Compounds, Heterocyclic; Butorphanol; Chronic Disease; Clinical Trials as Topic; Cycloparaffins; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Morphinans; Neoplasms; Pain; Random Allocation; Tetrahydronaphthalenes

The relative performance of three analgesic rating scales--visual pain analog, verbal pain intensity, and verbal pain relief--was assessed in clinical trials with 1,497 patients and a variety of pain models. The scales correlated strongly with one another, with inconsistent and generally minimal differences in sensitivity. Overall, the verbal relief scale tended to be slightly more sensitive than the pain analog rating, which in turn showed a small advantage over the verbal pain intensity assessment. When the scores derived from the categorized ratings 1 hour after drug dosing (generally the time of peak effect) were analyzed, there was little difference whether a parametric or nonparametric approach was taken. When the cumulative measures of overall effect over 6 hours were considered, however, the nonparametric approach was decidedly more powerful. There was a similar pattern when the analog scores were analyzed. This unanticipated finding appears to be due to the cumulative measures (from all three scales) being more skewed toward the lower end of their respective ranges than are the 1-hour scores. A composite efficacy variable was defined, incorporating data from the three primary scales; this measure was found to be generally comparable in sensitivity to the individual scales and may be useful as a global summary of response. While our investigation provides evidence that any of the ratings considered will accurately reflect analgesic response, the verbal relief scale was the most sensitive and might be the best choice if a single measure is desired.

Topics: Bridged Bicyclo Compounds, Heterocyclic; Butorphanol; Clinical Trials as Topic; Cycloparaffins; Double-Blind Method; Humans; Morphinans; Morphine; Pain; Pain, Postoperative; Tetrahydronaphthalenes

A double-blind, placebo-controlled crossover trial was carried out in 20 hospitalized patients with continuous pain due to cancer to assess the analgesic effectiveness and tolerance of a single intramuscular injection of 10 mg dezocine. Subjective assessments of pain, made at hourly intervals over 4 hours, showed that dezocine produces a statistically significant greater and sustained relief of pain than did placebo. Only minor side-effects were reported.

Topics: Bridged Bicyclo Compounds, Heterocyclic; Bridged-Ring Compounds; Clinical Trials as Topic; Cycloparaffins; Humans; Neoplasms; Pain; Placebos; Tetrahydronaphthalenes

The aim of this study was to explore the effects of dezocine combined with dexmedetomidine on adverse reactions and inflammatory factors in patients undergoing hyperthermic intraperitoneal chemotherapy (HIPEC) after intestinal surgery and its protective effect on the heart in the perioperative period.. A total of 80 patients treated with HIPEC after intestinal surgery in our hospital from September 2018 to December 2019 were enrolled as research subjects. All patients were evenly divided into two groups using a random number table. As to analgesia and sedation during treatment, dezocine was injected intramuscularly at 30 min before treatment in the control group. Meanwhile, dezocine combined with dexmedetomidine was given in the same way in the observation group. Adverse reactions and changes in numeric rating scale (NRS) pain score during intervention were compared between the two groups. The changes in the levels of inflammatory and myocardial injury-related factors, and vascular endothelial function and regeneration ability among cardiovascular indicators at 12 h after intervention were compared as well. Additionally, the correlations of left ventricular mass index (LVMI) with the changes in the levels of inflammatory factor high-sensitivity C-reactive protein (hs-CRP), myocardial injury-related factor lactic dehydrogenase (LDH), vascular endothelial function indicator endothelin-1 (ET-1) and cardiovascular regeneration ability index vascular endothelial growth factor (VEGF) were analyzed.. Compared with control group, the total prevalence rate of severe pain, respiratory depression, nausea and vomiting, diarrhea, and muscle rigidity during intervention was significantly reduced in the observation group (p<0.05). NRS pain score at 1, 4, 8 and 12 h after intervention decreased remarkably in the observation group compared with the control group (p<0.05). Meanwhile, the levels of inflammatory factors tumor necrosis factor-α (TNF-α) and hs-CRP, and myocardial injury-related factors LDH and creatine kinase MB (CKMB) as well as ET-1 at 12 h after intervention declined remarkably in observation group compared with control group (p<0.05). However, the levels of nitric oxide (NO), VEGF and basic fibroblast growth factor (bFGF) rose significantly in the observation group (p<0.05). Besides, LVMI was positively correlated with hs-CRP and LDH, whereas was negatively associated with ET-1 and VEGF (p<0.05).. In HIPEC, dezocine combined with dexmedetomidine used for sedation and analgesia is able to effectively reduce adverse reactions and relieve inflammatory responses in vivo, exerting a cardio-protective effect.

Topics: Bridged Bicyclo Compounds, Heterocyclic; C-Reactive Protein; Dexmedetomidine; Digestive System Surgical Procedures; Humans; Hyperthermic Intraperitoneal Chemotherapy; Pain; Perioperative Period; Tetrahydronaphthalenes; Vascular Endothelial Growth Factor A

To investigate the application value and safety of peripheral prostate nerve block (PPNB) combined with dezocine in transrectal prostate biopsy.. Using a random number table, we divided 97 patients undergoing prostate biopsy in our hospital from October 2018 to October 2020 into an experimental group (n = 49) and a control group (n = 48), the former anesthetized by PPNB combined with dezocine and the latter by PPNB only. We compared the hemodynamic indexes before operation, during puncturing and at 5 minutes after operation, the pain scores during the movement of the probe in the rectum, at puncturing and at 5 minutes after surgery, and the adverse reactions to anesthesia between the two groups of patients.. The heart rate was significantly lower in the experimental group than in the control during puncturing and at 5 minutes after operation (P < 0.05), while the mean arterial pressure (MAP) and blood oxygen saturation (SpO2) were remarkably higher in the former than in the latter group during puncturing (P < 0.05). The Visual Analogue Scale (VAS) score for pain was markedly lower in the experimental group than in the control during the movement of the probe in the rectum, at puncturing and at 5 minutes after surgery (P < 0.05). There was no statistically significant difference in the total incidence rate of adverse reactions to anesthesia between the two groups (P > 0.05).. PPNB combined with dezocine for prostate biopsy is more conducive to maintaining the stability of the patient's hemodynamics, and has a good analgesic effect and a high safety.

Topics: Anesthetics, Local; Biopsy; Humans; Lidocaine; Male; Nerve Block; Pain; Prostate

MicroRNAs (miRNAs) play important roles in drug tolerance and regulating pain. The purpose of the present study is to explore the regulatory mechanism of miR-124-3p on dezocine tolerance against pain in a rat model. The expression of miR-124-3p and TRAF6 in spinal cord of rats was detected by quantitative reverse-transcription PCR. The paw withdrawal latency (PWL) and maximal potential efficiency % of rats were detected by PWL assay. The levels of IL-1β and TNF-α in spinal cord tissues of rats were measured by ELISA assay. The interaction between TRAF6 and miR-124-3p was predicted by TargetScan software (http://www.targetscan.org) and confirmed by the dual-luciferase reporter assay. The protein level of TRAF6 was determined by western blot. MiR-124-3p expression was highly downregulated in a dezocine-resistant model. MiR-124-3p overexpression could alleviate dezocine tolerance in rats. TRAF6 expression was significantly upregulated in a dezocine-resistant model. MiR-124-3p targeted TRAF6 and TRAF6 was negatively modulated by miR-124-3p. In addition, overexpression of TRAF6 could reverse the inhibitory effects of miR-124-3p on dezocine tolerance. Overexpression of miR-124-3p alleviates dezocine tolerance against pain via regulating TRAF6 in a rat model, providing a possible solution to address dezocine tolerance in clinical.

Topics: Analgesics; Animals; Bridged Bicyclo Compounds, Heterocyclic; Disease Models, Animal; Drug Tolerance; Gene Expression Regulation; Male; MicroRNAs; Pain; Rats; Rats, Sprague-Dawley; Tetrahydronaphthalenes; TNF Receptor-Associated Factor 6

Topics: Adult; Analgesics, Opioid; Antiemetics; Bridged Bicyclo Compounds, Heterocyclic; Dexamethasone; Female; Humans; Injections, Intravenous; Male; Middle Aged; Pain; Pain Measurement; Perineum; Postoperative Nausea and Vomiting; Pruritus; Tetrahydronaphthalenes; Treatment Outcome

The aim of this study was to observe the analgesic effects of the combination of dezocine and butorphanol on postoperative cognitive function in elderly patients. Forty elderly patients undergoing upper abdominal surgeries or thoracotomies with general anesthesia were randomly divided into the dezocine and butorphanol group or the butorphanol group (20 patients per group). A visual analog scale was used to evaluate analgesia and the degree of malignant vomiting. The Ramsay scoring method was used to evaluate sedation. The Mini-Mental State Examination (MMSE) was used to evaluate cognitive function. Forty-eight hours after the operation, the pain score of the dezocine and butorphanol group (means ± SD, 1.75 ± 0.44) was lower than that of the butorphanol group (2.25 ± 0.79; P < 0.05), and the nausea and vomiting score of the dezocine and butorphanol group (0) was lower than that of the butorphanol group (0.70 ± 1.30; P < 0.05). Six hours after the operation, the sedative score of the butorphanol group (3.75 ± 0.79) was higher than that of the dezocine and butorphanol group (2.15 ± 0.75; P < 0.05). Compared to 1 day before the operation, the MMSE scores of both groups decreased 6 h after the operation, and the MMSE score of the butorphanol group (15.00 ± 2.00) was lower than that of the dezocine and butorphanol group (20.95 ± 1.54; P < 0.05). Dezocine and butorphanol analgesia had transient effects on postoperative cognitive function in elderly patients, and the effect of the combination was superior than butorphanol only.

Topics: Aged; Aged, 80 and over; Anesthesia, Intravenous; Bridged Bicyclo Compounds, Heterocyclic; Butorphanol; Cognition; Female; Humans; Hypnotics and Sedatives; Male; Pain; Postoperative Complications; Tetrahydronaphthalenes; Thoracotomy

We examined the effects of several opioids that vary in intrinsic efficacy at the mu-opioid receptor alone and in combination with morphine in a rat warm water tail withdrawal procedure using 50 degrees C and 52 degrees C water (i.e., low- and high-stimulus intensities). Morphine, levorphanol, dezocine, and buprenorphine produced dose-dependent increases in antinociception using both stimulus intensities. Butorphanol produced maximal levels of antinociception at the low, but not at the high, stimulus intensity, whereas nalbuphine failed to produce antinociception at either stimulus intensity. For cases in which butorphanol and nalbuphine failed to produce antinociception alone, these opioids dose-dependently antagonized the effects of morphine. When levorphanol, dezocine, and buprenorphine were combined with morphine, there was a dose-dependent enhancement of morphine's effects. Similar effects were obtained at the low-stimulus intensity when butorphanol was administered with morphine. In most cases, the effects of these combinations could be predicted by summating the effects of the drugs when administered alone. These results indicate that the level of antinociception produced by an opioid is dependent on the intrinsic efficacy of the drug and the stimulus intensity. Furthermore, the level of antinociception produced by the opioid, not necessarily the opioids' intrinsic efficacy, determines the type of interaction among opioids.. Compared with high-efficacy opioids, lower efficacy opioids produce lower levels of pain relief, especially in situations of moderate to severe pain. When opioids are given in combination, the effects can only be predicted on the basis of the antinociception obtained when the drugs are administered alone.

Topics: Analgesics, Opioid; Animals; Bridged Bicyclo Compounds, Heterocyclic; Buprenorphine; Butorphanol; Cycloparaffins; Dose-Response Relationship, Drug; Drug Combinations; Levorphanol; Morphine; Nalbuphine; Narcotics; Nociceptors; Pain; Physical Stimulation; Rats; Rats, Long-Evans; Receptors, Opioid, mu; Tetrahydronaphthalenes