Postoperative analgesia using dezocine alleviates depressive symptoms after colorectal cancer surgery: A randomized, controlled, double-blind trial

Zhao, Peng; Wu, Zhuoxi; Li, Chunrui; Yang, Guanlin; Wang, Kai; Wang, Mingming; Feng, Lijuan; Duan, Guangyou; Li, Hong

doi:10.1371/journal.pone.0233412

Cited by 17 publications

(11 citation statements)

References 42 publications

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“…Dezocine has been found to inhibit both the serotonin and norepinephrine uptake transporters [1]. This led to the investigation and discovery that dezocine has antidepressant activity in patients treated post-operatively for pain [22]. Anti-depressant activity of dezocine was also verified in a rodent model [23].…”

Section: Discussionmentioning

confidence: 99%

Dezocine is a Biased Ligand without Significant Beta-Arrestin Activation of the mu Opioid Receptor

Grothusen¹,

Lin²,

Jin³

et al. 2022

Transl Perioper & Pain Med

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Dezocine is an opioid that was used in clinical practice for acute pain management in the US (1986US ( to 2011 and is currently in use in China. It is not listed as a controlled substance in the US due to no reported cases of addiction. Dezocine is a partial agonist at the mu opioid receptor (MOR); however, it is unclear whether dezocine can activate both the G protein pathway and the beta-arrestin pathway. In this study we hypothesized that dezocine does not activate the beta-arrestin pathway, which could be the potential molecular mechanism by which dezocine is not addictive or at least less addictive than other classic opioids. Both morphine, a MOR full agonist and buprenorphine, a partial MOR agonist similar to dezocine, were used for comparison purposes. The major side effects of dezocine in clinical usage are its gastrointestinal side effects and first pass effects; therefore, we explored the possibility of administering dezocine intranasally in rodents to demonstrate the feasibility of intranasal administration for new clinical usage purposes. With proper formulation it is possible to administer dezocine intranasally to achieve a high concentration in the brain in the rodent model. The results indicate that dezocine does not activate the betaarrestin pathway in MOR. Intranasal delivery of dezocine achieves a much higher medication concentration in the blood and brain as compared to intraperitoneal injection. It also persists a longer time before it falls below detection in the blood. This study provides a possible explanation of why dezocine is not addictive or at least less addictive than other commonly used opioids. This study also demonstrates that intranasal administration offers an alternative strategy for its potential clinical applications. MethodsAll the chemicals used in this study were commercially obtained and were either analytical or pharmaceutical grade with more than 98% purity. Nanodezocine (dezocine complexed with 2-hydroxypropylγ-cyclodextrin) is a patented formulation produced in our laboratory [9]. HTLA cells, an HEK293 cell line stably expressing a tTA-dependent luciferase reporter and a beta-arrestin-TEV fusion gene, were kindly provided by the laboratory of Bryan L. Roth MD, PhD at the University of North Carolina at Chapel Hill [10]. The animal protocols were approved by the Institutional

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Section: Discussionmentioning

confidence: 99%

Dezocine is a Biased Ligand without Significant Beta-Arrestin Activation of the mu Opioid Receptor

Grothusen¹,

Lin²,

Jin³

et al. 2022

Transl Perioper & Pain Med

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“…Dezocine is a potent opioid analgesic with both exciting and antagonistic effects ( 12 ). On the one hand, dezocine mainly achieves analgesic and sedative effects by exciting K receptors distributed in the brain, spinal cord, and brain stem ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

Comparative Study of Dezocine and Ketorolac Tromethamine in Patient-Controlled Intravenous Analgesia of Laparoscopic Cholecystectomy

et al. 2022

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PurposeThis study aimed to observe the application value of dezocine and ketorolac tromethamine in patient-controlled intravenous analgesia (PCIA) of patients undergoing laparoscopic cholecystectomy (LC).MethodsA total of 154 patients who underwent LC surgery in our hospital and received PCIA after surgery from September 2020 to September 2021 were selected, they were divided into group A (n = 77) and group B (n = 77). Group A was given dezocine and group B was given ketorolac tromethamine. The analgesia, sedation, comfort, and adverse reactions of the two groups were closely observed at 4, 8, 12, and 24 h after surgery.ResultsAt 4, 8, 12, and 24 h after surgery, the visual analog scale scores in group B were lower than those in group A (P < 0.05). At 4, 8, 12, and 24 h after surgery, the Ramsay scores in group B were higher than those in group A (P < 0.05). At 4, 8, 12, and 24 h after surgery, there was no significant difference in Bruggrmann comfort scale scores between the two groups (P > 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05).ConclusionBoth dezocine and ketorolac tromethamine have high clinical application value in patients who underwent LC surgery and received PCIA, with higher patient comfort and fewer adverse reactions. But compared with dezocine, ketorolac tromethamine can achieve better sedative and analgesic effects, which is worthy of clinical promotion.

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“…74 Zhao et al also confirmed this finding in patients after colon cancer surgery. 75 These results suggest that dezocine has an antidepressant effect both in cancer patients undergoing surgery and in pregnant women undergoing cesarean section. An experimental study has found that dezocine exerts antidepressant-like effects in mice through the involvement of 5-HT1A and κ opioid receptors.…”

Section: Dezocine Has Potential To Regulate the Clinical And Biologic...mentioning

confidence: 94%

Dezocine Has the Potential to Regulate the Clinical and Biological Features of Tumors

Hu¹,

Liu²,

Qiu³

et al. 2022

DDDT

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Cancer is the second leading cause of death following ischemic heart disease in the world and the primary clinical, social and economic burden. Surgical resection is the main measure for the treatment of the vast majority of solid tumors. However, the recurrence and metastasis of tumors occur at different periods after surgery in many cases undergoing radical tumor surgery, which is the main cause of death of tumor patients. Moreover, tumor patients are prone to suffer from mental depression, which may increase the morbidity and mortality of tumors. Tumors have a series of clinical biological signs with the following five main features: postoperative pain and cancerous pain; suppression of antitumor immunity; angiogenesis in tumors; proliferation, growth and metastasis of tumors; and mental depression. Surgery is the first treatment in the majority of cancer patients with solid tumors. Opioids are required for anesthesia and postoperative analgesia. For cancerous pain control, patients undergo surgery, and their quality of life of is improved. However, traditional opioids, such as morphine, may inhibit antitumor immunity, induce vascular growth of tumors and promote the proliferation, invasion and migration of cancer cells, and traditional opioids can induce a risk of somatic dependence. However, studies have found that not all opioids share the effects of immunosuppression, tumor proliferation promotion and angiogenesis induction. Dezocine, a novel opioid with specific pharmacological mechanisms, has been demonstrated to regulate the five clinical and biological features of tumors. We reviewed the preclinical and clinical studies of dezocine on postoperative pain and cancer pain in tumor patients as well as the immune system, tumor angiogenesis, tumor proliferation, tumor growth, tumor metastasis and mental depression. We proposed that dezocine may be the best choice of opioids for anesthesia and analgesia in cancer patients.

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Postoperative analgesia using dezocine alleviates depressive symptoms after colorectal cancer surgery: A randomized, controlled, double-blind trial

Cited by 17 publications

References 42 publications

Dezocine is a Biased Ligand without Significant Beta-Arrestin Activation of the mu Opioid Receptor

Dezocine is a Biased Ligand without Significant Beta-Arrestin Activation of the mu Opioid Receptor

Comparative Study of Dezocine and Ketorolac Tromethamine in Patient-Controlled Intravenous Analgesia of Laparoscopic Cholecystectomy

Dezocine Has the Potential to Regulate the Clinical and Biological Features of Tumors

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