Dual μ-opioid receptor and norepinephrine reuptake mechanisms contribute to dezocine- and tapentadol-induced mechanical antiallodynia in cancer pain
| Autor: | Meng-Jing Zhao, Xin-Yan Li, Yong-Xiang Wang, Xue-Qi Tang, Muhammad Zaeem Ahsan, Xiao-Fang Mao, Evhy Apryani |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Tetrahydronaphthalenes medicine.drug_class Analgesic Receptors Opioid mu Bone Neoplasms Pharmacology Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Phentolamine Opioid receptor Naltrindole Cell Line Tumor medicine Animals Rats Wistar Serotonin and Noradrenaline Reuptake Inhibitors Injections Spinal Behavior Animal Dose-Response Relationship Drug business.industry Cancer Pain Bridged Bicyclo Compounds Heterocyclic Tapentadol Receptor antagonist Rats Dezocine Analgesics Opioid 030104 developmental biology Hyperalgesia Neuropathic pain Female business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | European Journal of Pharmacology. 876:173062 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2020.173062 |
| Popis: | Dezocine is an opioid analgesic widely used in China, occupying over 45% of the domestic market of opioid analgesics. We have recently demonstrated that dezocine produced mechanical antiallodynia and thermal antihyperalgesia through spinal μ-opioid receptor activation and norepinephrine reuptake inhibition in neuropathic pain. This study further explored the dual μ-opioid receptor and norepinephrine reuptake mechanisms underlying dezocine-induced mechanical antiallodynia in bone cancer pain, compared with tapentadol, the first recognized analgesic in this class. Dezocine and tapentadol, given subcutaneously, exerted profound mechanical antiallodynia in bone cancer pain rats in a dose-dependent manner, yielding similar maximal effects but different potencies: ED50s of 0.6 mg/kg for dezocine and 7.5 mg/kg for tapentadol, respectively. Furthermore, their mechanical antiallodynia was partially blocked by intrathecal injection of the specific μ-opioid receptor antagonist CTAP, but not κ-opioid receptor antagonists GNTI and nor-BNI or δ-opioid receptor antagonist naltrindole. Intrathecal administrations of the specific norepinephrine depletor 6-OHDA (but not the serotonin depletor PCPA) for three consecutive days and single injection of the α-adrenoceptor antagonist phentolamine/α2-adrenoceptor antagonist yohimbine partially blocked dezocine- and tapentadol-induced mechanical antiallodynia. Strikingly, the combination of CTAP and yohimbine nearly completely blocked dezocine- and tapentadol-induced mechanical antiallodynia. Our results illustrate that both dezocine and tapentadol exert mechanical antiallodynia in bone cancer pain through dual mechanisms of μ-opioid receptor activation and norepinephrine reuptake inhibition, and suggest that the μ-opioid receptor and norepinephrine reuptake dual-targeting opioids are effective analgesics in cancer pain. |
| Databáze: | OpenAIRE |
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