Miranda Hugo F, Noriega Viviana, Zanetta Pilar, Prieto Juan Carlos, Prieto-Rayo Juan Carlos, Aranda Nicolás, Sierralta Fernando
J Biomed Sci. 2014 Jul 15;21(1):62. doi: 10.1186/s12929-014-0062-6.
Opioids have been used for the management of pain and coadministration of two opioids may induce synergism. In a model of tonic pain, the acetic acid writhing test and in a phasic model, the hot plate, the antinociceptive interaction between fentanyl, methadone, morphine, and tramadol was evaluated.
The potency of opioids in the writhing test compared to the hot plate assay was from 2.5 (fentanyl) to 15.5 (morphine) times, respectively. The ED50 was used in a fixed ratio for each of the six pairs of opioid combinations, which, resulted in a synergistic antinociception except for methadone/tramadol and fentanyl/tramadol which were additive, in the hot plate. The opioid antagonists naltrexone, naltrindole and nor-binaltorphimine, suggests that the synergism of morphine combinations are due to the activation of MOR subtypes with partially contribution of DOR and KOR, however fentanyl and methadone combinations are partially due to the activation of MOR and DOR subtypes and KOR lack of participation. The antinociceptive effects of tramadol combinations, are partially due to the activation of MOR, DOR and KOR opioid subtypes.
These results suggets that effectiveness and magnitude of the interactions between opioids are dependent on pain stimulus intensity.
阿片类药物已被用于疼痛管理，两种阿片类药物的联合使用可能会产生协同作用。在强直性疼痛模型（醋酸扭体试验）和阶段性疼痛模型（热板试验）中，评估了芬太尼、美沙酮、吗啡和曲马多之间的抗伤害感受相互作用。
与热板试验相比，阿片类药物在扭体试验中的效价分别为2.5（芬太尼）至15.5（吗啡）倍。对于六对阿片类药物组合中的每一对，均以固定比例使用半数有效剂量（ED50），结果除美沙酮/曲马多和芬太尼/曲马多在热板试验中为相加作用外，其余均产生协同抗伤害感受。阿片类拮抗剂纳曲酮、纳曲吲哚和去甲二氢吗啡酮表明，吗啡组合的协同作用是由于μ阿片受体（MOR）亚型的激活，同时δ阿片受体（DOR）和κ阿片受体（KOR）也有部分贡献，然而芬太尼和美沙酮组合部分是由于MOR和DOR亚型的激活，KOR未参与。曲马多组合的抗伤害感受作用部分是由于MOR、DOR和KOR阿片受体亚型的激活。
这些结果表明，阿片类药物之间相互作用的有效性和强度取决于疼痛刺激强度。
