Ketamine-Induced Potentiation of Morphine Analgesia in Rat Tail-Flick Test : Role of Opioid-, α_2-Adrenoceptors and ATP-Sensitive Potassium Channels(Pharmacology)

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概要

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• Ketamine is known to improve opioid efficacy, reduce postoperative opioid requirement and oppose opioid associated pain hypersensitivity and tolerance. However, the mechanisms underlying these beneficial effects are not clear. This study investigated the effects of ketamine at a non-analgesic dose (30mg/kg, i.p.) on analgesia induced by morphine (2.5, 5.0, 7.5mg/kg, s.c.), using rat tail-flick test as an animal model of acute pain. Further, the role of opioid-, α_2-adrenoceptors and ATP-sensitive potassium channels was examined on the potentiating effect of ketamine. Male rats received morphine alone at 5.0 and 7.5 but not at 2.5mg/kg showed a dose-related increase in tail-flick latencies. The combination of morphine and ketamine resulted in dose-related increase in morphine analgesia, both on the intensity as well as on duration. The ketamine-induced potentiation of morphine (7.5mg/kg) analgesia was unaffected by glibenclamide (3mg/kg, s.c.) and only partially blocked by yohimbine (2mg/kg, i.p.), but more completely abolished by naloxone (2mg/kg, i.p.). Both morphine (5.0mg/kg) and ketamine (30mg/kg) alone did not evoke catalepsy in rats but on combination produced a synergistic effect, which was however, abolished by naloxone pretreatment. In the open-field test, while morphine (5.0mg/kg) caused a depressant effect, ketamine (30mg/kg) enhanced the locomotor activity. Nevertheless, in combination potentiated the morphine's depressant effect on locomotion, which was also antagonized by naloxone. These results indicate that ketamine at a non-analgesic dose can potentiate morphine analgesia, induce catalepsy and cause locomotor depression, possibly involving an opioid mechanism. This potentiation, although favorable in acute pain management, may have some adverse clinical implications.

• 公益社団法人日本薬学会の論文
• 2006-01-01

著者

• Santos Flavia

  Department Of Physiology And Pharmacology Post-graduate Programme In Medical Sciences Faculty Of Med

• Rao Vietla

  Departament Of Physiology And Pharmacology Federal University Of Ceara (fm)

• CAMPOS Adriana

  Departament of Physiology and Pharmacology, Federal University of Ceara (FM)

• Campos Adriana

  Departament Of Physiology And Pharmacology Federal University Of Ceara (fm)

• Santos Flavia

  Departament Of Physiology And Pharmacology Federal University Of Ceara (fm)

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