Ballet S, Mauborgne A, Hamon M, Cesselin F, Collin E
NeuroPsychoPharmacologie Moléculaire, Cellulaire et Fonctionnelle, INSERM U288, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Synapse. 2000 Sep 15;37(4):262-72. doi: 10.1002/1098-2396(20000915)37:4<262::AID-SYN3>3.0.CO;2-6.
Previous studies showed that spinal opioidergic neurotransmission is markedly altered in the polyarthritic rat, a model of chronic inflammatory pain. Present investigations aimed at assessing possible changes in opioid-mediated control of the spinal outflow of met-enkephalin (ME) and dynorphin (DYN) in these animals. Intrathecal (i.t.) perfusion under halothane anesthesia showed that polyarthritis was associated with both a 40% decrease in the spinal outflow of ME-like material (MELM) and a 90% increase in that of DYNLM. Local treatment with the mu-opioid agonist DAGO (10 microM i.t.) inhibited equally (-30%) the MELM outflow in polyarthritic and control rats, whereas the delta agonist DTLET (10 microM i.t.) also reduced the peptide outflow in controls (-27%) but enhanced it in polyarthritic animals (+56%). On the other hand, both DAGO (10 microM i.t.) and DTLET (10 microM i.t.) decreased (-40 and -49%) DYNLM outflow in polyarthritic rats, but were inactive in controls. Finally, neither MELM outflow nor that of DYNLM were affected by the kappa-agonist U50488H (10 microM i.t.) in both groups of rats. In all cases, the changes due to active agonists could be prevented by specific antagonists which were inactive on their own except the kappa antagonist nor-binaltorphimine (10 microM i.t.) that decreased (-38%) DYNLM outflow in polyarthritic rats. These data indicate that functional changes in spinal opioid receptors may promote enkephalinergic neurotransmission and reduce dynorphinergic neurotransmission in polyarthritic rats, thereby contributing to the analgesic efficacy of opioids in inflammatory pain.
先前的研究表明，在慢性炎性疼痛模型——多关节炎大鼠中，脊髓阿片能神经传递发生了显著改变。目前的研究旨在评估这些动物中阿片介导的甲硫氨酸脑啡肽（ME）和强啡肽（DYN）脊髓传出控制的可能变化。在氟烷麻醉下进行鞘内（i.t.）灌注显示，多关节炎与ME样物质（MELM）脊髓传出减少40%以及DYNLM脊髓传出增加90%相关。用μ阿片激动剂DAGO（10μM，i.t.）进行局部治疗，在多关节炎大鼠和对照大鼠中对MELM传出的抑制程度相同（-30%），而δ激动剂DTLET（10μM，i.t.）在对照大鼠中也减少了肽的传出（-27%），但在多关节炎动物中却增强了肽的传出（+56%）。另一方面，DAGO（10μM，i.t.）和DTLET（10μM，i.t.）都使多关节炎大鼠的DYNLM传出减少（-40%和-49%），但在对照大鼠中无作用。最后，κ激动剂U50488H（10μM，i.t.）在两组大鼠中对MELM传出和DYNLM传出均无影响。在所有情况下，可以通过特异性拮抗剂阻止活性激动剂引起的变化，这些拮抗剂自身无活性，除了κ拮抗剂nor - binaltorphimine（10μM，i.t.）使多关节炎大鼠的DYNLM传出减少（-38%）。这些数据表明，脊髓阿片受体的功能变化可能促进多关节炎大鼠中的脑啡肽能神经传递并减少强啡肽能神经传递，从而有助于阿片类药物在炎性疼痛中的镇痛效果。
