Braz J, Beaufour C, Coutaux A, Epstein A L, Cesselin F, Hamon M, Pohl M
Institut National de la Santé et de la Recherche Médicale U288, NeuroPsychoPharmacologie Moléculaire, Cellulaire, et Fonctionnelle and Service de Rhumatologie, Hôpital Pitié-Salpêtrière, 75013 Paris, France.
J Neurosci. 2001 Oct 15;21(20):7881-8. doi: 10.1523/JNEUROSCI.21-20-07881.2001.
Rheumatoid arthritis is characterized by erosive inflammation of the joints, new bone proliferation, and ankylosis, leading to severely reduced locomotion and intense chronic pain. In a model of this disease, adjuvant-induced polyarthritis in the rat, neurons involved in pain transmission and control undergo plastic changes, especially at the spinal level. These changes affect notably neurons that contain opioids, such as enkephalins deriving from preproenkephalin A (PA) precursor protein. Using recombinant herpes simplex virus containing rat PA cDNA, we enhanced enkephalin synthesis in sensory neurons of polyarthritic rats. This treatment markedly improved locomotion and reduced hyperalgesia. Furthermore, the progression of bone destruction slowed down, which is the most difficult target to reach in the treatment of patients suffering from arthritis. These data demonstrate the therapeutic efficacy of enkephalin overproduction in a model of systemic inflammatory and painful chronic disorder.
类风湿性关节炎的特征是关节出现侵蚀性炎症、新骨增生和关节强直，导致运动能力严重下降和剧烈的慢性疼痛。在这种疾病的一个模型中，即大鼠佐剂诱导性多关节炎模型，参与疼痛传递和控制的神经元会发生可塑性变化，尤其是在脊髓水平。这些变化尤其影响含有阿片类物质的神经元，例如源自前脑啡肽原A（PA）前体蛋白的脑啡肽。我们使用含有大鼠PA cDNA的重组单纯疱疹病毒，增强了多关节炎大鼠感觉神经元中脑啡肽的合成。这种治疗显著改善了运动能力并减轻了痛觉过敏。此外，骨破坏的进程减缓，而这是关节炎患者治疗中最难实现的目标。这些数据证明了在全身性炎症和疼痛性慢性疾病模型中，脑啡肽过量产生的治疗效果。
