Dual μ-opioid receptor and norepinephrine reuptake mechanisms contribute to dezocine- and tapentadol-induced mechanical antiallodynia in cancer pain

Mao, Xiao-Fang; Ahsan, Muhammad Zaeem; Apryani, Evhy; Tang, Xue-Qi; Zhao, Min; Li, Xinyan; Wang, Yongxiang

doi:10.1016/j.ejphar.2020.173062

Cited by 12 publications

(14 citation statements)

References 60 publications

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“… 16 , 17 Dezocine is a partial μ receptor agonist and partial κ receptor agonist, which can inhibit the uptake of serotonin and epinephrine, similar to tramadol, and may have a similar protective effect on immunity. 32 , 33 Studies have found that dezocine can up-regulate the level of IL-12 and down-regulate the level of IL-10 in human umbilical cord blood dendritic cells, 34 improve the proliferation and cytotoxicity of CD8 + cells, promote the maturation of BMDC, and inhibit tumor metastasis in rats. 35 , 36 …”

Section: Introductionmentioning

confidence: 99%

“…protective effect on immunity. 32,33 Studies have found that dezocine can up-regulate the level of IL-12 and downregulate the level of IL-10 in human umbilical cord blood dendritic cells, 34 improve the proliferation and cytotoxicity of CD8 + cells, promote the maturation of BMDC, and inhibit tumor metastasis in rats. 35,36 Wang et al found that the postoperative analgesic effect for breast cancer patients is slightly better with sufentanil than with dezocine.…”

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confidence: 99%

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Effects of Dezocine and Sufentanil on Th1/Th2 Balance in Breast Cancer Patients Undergoing Surgery

Hu¹,

Liu²,

Wu³

et al. 2021

DDDT

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Background: It is very important for breast cancer patients undergoing surgery to choose an opioid that has little effect on the immune system. The aim of this study is to compare the effects of dezocine or sufentanil on postoperative pain and Th1/Th2 balance in patients undergoing breast cancer surgery. Methods: Data from 92 breast cancer patients from January 2019 to July 2020 at Foshan Second People's Hospital (Guangdong, China) were analyzed. Sufentanil (SF) was used in group SF (n = 44) and dezocine (DE) in group DE (n = 48). The Visual Analog Scale (VAS) scores were assessed, and the percentages of Th1 cells and Th2 cells in peripheral blood were detected before anesthesia and at 2, 12, 24, and 48 hours after surgery. Results: There was no significant difference in the VAS scores between the two groups at 2, 24, and 48 hours after surgery (P > 0.05). The VAS scores at 12 hours after surgery in group DE were significantly lower than those in group SF with a statistically significant difference (P < 0.05). The percentage of Th1 cells in group DE at 2, 12, 24, and 48 hours after surgery was significantly lower than that in group SF (P < 0.05). The percentage of Th2 cells in group DE at 2, 12, 24, and 48 hours after surgery was significantly lower than that in group SF (P < 0.05). The Th1/Th2 ratio at 2, 12, 24, and 48 hours after surgery was significantly higher in group DE than that in group SF (P < 0.05). Conclusion: Dezocine for anesthesia induction and postoperative analgesia can maintain the balance of Th1/Th2 more stable than, with the same analgesia efficacy as, sufentanil during the early postoperative period in breast cancer patients undergoing surgery.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Effects of Dezocine and Sufentanil on Th1/Th2 Balance in Breast Cancer Patients Undergoing Surgery

Hu¹,

Liu²,

Wu³

et al. 2021

DDDT

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“…Cancer pain is a mix pain and cancer patients usually suffer from nociceptive pain and neuropathic pain (Gutgsell et al, 2003). The agonism of μ‐receptors governs acute nociceptive pain, whereas activation of κ‐receptors alleviates chronic neuropathic pain (Mao et al, 2020; Moon et al, 2016; Sounvoravong et al, 2004; Sun et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Protopanaxadiol alleviates neuropathic pain by spinal microglial dynorphin A expression following glucocorticoid receptor activation

Shoaib

Ahmad

Wang

2021

British J Pharmacology

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Background and Purpose: New remedies are required for the treatment of neuropathic pain due to insufficient efficacy of available therapies. This study provides a novel approach to develop painkillers for chronic pain treatment.Experimental Approach: The rat formalin pain test and spinal nerve ligation model of neuropathic pain were used to evaluate antinociception of protopanaxadiol. Primary cell cultures, immunofluorescence staining, and gene and protein expression were also performed for mechanism studies.Key Results: Gavage protopanaxadiol remarkably produces pain antihypersensitive effects in neuropathic pain, bone cancer pain and inflammatory pain, with efficacy comparable with gabapentin. Long-term PPD administration does not induce antihypersensitive tolerance, but prevents and reverses the development and expression of morphine analgesic tolerance. Oral protopanaxadiol specifically stimulates spinal expression of dynorphin A in microglia but not in astrocytes or neurons.

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“…This effect presented no signs of tolerance, and the authors surmised that dezocine could be considered an alternative medication for treating NP ( Wu et al, 2019 ). Moreover, a recent study reported that subcutaneous injection of dezocine inhibited NP in patients with cancer in a time-dependent manner ( Mao et al, 2020 ). However, the effect of dezocine in treating NP is not fully clear.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of RAPGEF3 enhances the therapeutic effect of dezocine in treatment of neuropathic pain

Xue

Song

et al. 2021

Genet. Mol. Biol.

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Pain is a significant problem worldwide that affects the quality of life of patients. Dezocine is a non-addictive analgesic drug with kappa-opioid antagonist activity and has been successfully used to alleviate of postoperative pain. In addition, dezocine has an analgesic effect similar to that of morphine, alleviating moderate to severe pain. Rap guanine nucleotide exchange factor 3 (RAPGEF3) is a guanine nucleotide exchange factor for GTPases Rap1 and Rap2, which could enhance the activity of Rap1 to promote cell adhesion and axon regeneration, as well as promote neurite extension by interacting with nerve growth factors. Here, we first observed that overexpression of RAPGEF3 increased cell viability, as shown by a CCK-8 assay, and recovered brain function in rats. The expression of inflammation-related factors at the mRNA level was detected using qPCR, and the concentration of these factors in a cultured cell medium and rat serum samples were decreased as shown by ELISA after RAPGEF3 overexpression. Through western blotting, we further found that pro-inflammatory proteins were decreased, and these effects might be mediated by inhibition of the Ras/p-38 MAPK signaling pathway. Taken together, we speculated that RAPGEF3overexpression enhances the therapeutic effect of dezocine on neuropathic pain by inhibiting the inflammatory response through inhibition of the Ras/p-38 MAPK signaling pathway.

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Dual μ-opioid receptor and norepinephrine reuptake mechanisms contribute to dezocine- and tapentadol-induced mechanical antiallodynia in cancer pain

Cited by 12 publications

References 60 publications

Effects of Dezocine and Sufentanil on Th1/Th2 Balance in Breast Cancer Patients Undergoing Surgery

Effects of Dezocine and Sufentanil on Th1/Th2 Balance in Breast Cancer Patients Undergoing Surgery

Protopanaxadiol alleviates neuropathic pain by spinal microglial dynorphin A expression following glucocorticoid receptor activation

Overexpression of RAPGEF3 enhances the therapeutic effect of dezocine in treatment of neuropathic pain

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