Buritova J, Chapman V, Honoré P, Besson J M
Laboratoire de Physiopharmacologie du Système Nerveux INSERM U161 and EPHE, Paris, France.
Neuroscience. 1996 Jul;73(2):487-96. doi: 10.1016/0306-4522(96)00071-1.
In this pharmacological study we have assessed the effect of baclofen, a selective GABAB receptor agonist, on spinal expression of the immediate early gene c-Fos and the peripheral oedema evoked by a prolonged peripheral inflammation due to intraplantar carrageenan. Baclofen was administered intravenously 30 min before intraplantar injection of carrageenan in freely moving rats. Three hours after carrageenan the number of spinal c-Fos protein-like immunoreactive neurons and peripheral (ankle and paw) oedema were assessed. For the two series of experiments the total number of control carrageenan-evoked c-Fos protein-like immunoreactive neurons in segments L4-L5 of the spinal cord was 176 +/- 6 and 177 +/- 9 c-Fos protein-like immunoreactive neurons per section, for carrageenan control with intravenous and intraplantar saline, respectively. c-Fos protein-like immunoreactive neurons were predominantly located in laminae I-II and V-VI of the dorsal horn of the spinal cord in carrageenan controls receiving intravenous (68 +/- 3 and 69 +/- 2 c-Fos protein-like immunoreactive neurons, respectively) and intraplantar (62 +/- 4 and 71 +/- 5 c-Fos protein-like immunoreactive neurons, respectively) saline. Pre-administered systemic baclofen (0.05, 1.5 and 3 mg/kg i.v.) dose dependently reduced the total number of c-Fos protein-like immunoreactive neurons (81 +/- 3, 66 +/- 4 and 49 +/- 4% of control total number of c-Fos protein-like immunoreactive neurons, respectively), with strongest effects on the number of deep (74 +/- 3, 60 +/- 3 and 43 +/- 4% of control, respectively) as compared with superficial (90 +/- 4, 77 +/- 5 and 59 +/- 5% of control, respectively) c-Fos protein-like immunoreactive neurons. The effects of systemic baclofen on the carrageenan-induced spinal c-Fos expression and both the paw and ankle oedema were positively correlated (r = 0.479, P < 0.05 and r = 0.733, P < 0.001, respectively). Intraplantar baclofen (50 and 100 micrograms in 50 microliters of saline), simultaneously injected with intraplantar carrageenan, did not significantly influence carrageenan-evoked spinal c-Fos expression or ankle oedema. Despite the fact that the highest dose of intraplantar baclofen significantly reduced paw oedema (23 +/- 3% reduction of control paw oedema), our results are clearly in favour of a spinal site of action of systemic baclofen.
在本药理学研究中，我们评估了选择性GABAB受体激动剂巴氯芬对即刻早期基因c-Fos在脊髓中的表达以及由足底注射角叉菜胶引起的长时间外周炎症所诱发的外周水肿的影响。在自由活动的大鼠足底注射角叉菜胶前30分钟静脉注射巴氯芬。角叉菜胶注射3小时后，评估脊髓中c-Fos蛋白样免疫反应性神经元的数量以及外周（踝关节和爪）水肿情况。在两个系列的实验中，对于静脉注射生理盐水和足底注射生理盐水作为角叉菜胶对照的情况，脊髓L4-L5节段中角叉菜胶诱发的c-Fos蛋白样免疫反应性神经元的总数分别为每切片176±6个和177±9个c-Fos蛋白样免疫反应性神经元。在接受静脉注射（分别为68±3个和69±2个c-Fos蛋白样免疫反应性神经元）和足底注射（分别为62±4个和71±5个c-Fos蛋白样免疫反应性神经元）生理盐水的角叉菜胶对照中，c-Fos蛋白样免疫反应性神经元主要位于脊髓背角的I-II层和V-VI层。预先给予全身性巴氯芬（0.05、1.5和3mg/kg静脉注射）剂量依赖性地减少了c-Fos蛋白样免疫反应性神经元的总数（分别为对照c-Fos蛋白样免疫反应性神经元总数的81±3%、66±4%和49±4%），与浅层（分别为对照的90±4%、77±5%和59±5%）相比，对深层c-Fos蛋白样免疫反应性神经元数量的影响更强（分别为对照的74±3%、60±3%和43±4%）。全身性巴氯芬对角叉菜胶诱导的脊髓c-Fos表达以及爪和踝关节水肿的影响呈正相关（分别为r = 0.479，P < 0.05和r = 0.733，P < 0.001）。与足底注射角叉菜胶同时注射的足底巴氯芬（50微升生理盐水中含50和100微克），对角叉菜胶诱发的脊髓c-Fos表达或踝关节水肿没有显著影响。尽管足底巴氯芬的最高剂量显著减轻了爪水肿（对照爪水肿减少23±3%），但我们的结果明确支持全身性巴氯芬的脊髓作用部位。
