Legangneux E, Mora J J, Spreux-Varoquaux O, Thorin I, Herrou M, Alvado G, Gomeni C
Department of Psychiatry, University of Caen, France.
Rheumatology (Oxford). 2001 Mar;40(3):290-6. doi: 10.1093/rheumatology/40.3.290.
Primary fibromyalgia syndrome (PFS) is a chronic disorder commonly seen in rheumatological practice. The pathophysiological disturbances of this syndrome, which was defined by the American College of Rheumatology in 1990, are poorly understood. This study evaluated, in 30 patients, the hypothesis that PFS is a pain modulation disorder induced by deregulation of serotonin metabolism.
To compare platelet [(3)H]imipramine binding sites and serotonin (5-HT) levels in plasma-rich platelets (PRP) of PFS patients with those of matched healthy controls and to compare the levels of biogenic amine metabolites in the cerebrospinal fluid (CSF) of PFS patients with those of matched controls.
Platelet [(3)H]imipramine binding sites were defined by two criteria, B(max) for their density and K(d) for their affinity. PRP 5-HT and CSF metabolites of 5-HT (5-hydroxyindoleacetic acid, 5-HIAA), norepinephrine (3-methoxy, 4-hydroxy phenylglycol, MHPG) and dopamine (homovanillic acid, HVA) were assayed by reversed-phase high-performance liquid chromatography with coulometric detection.
[(3)H]Imipramine platelet binding was similar (P=0.43 for B(max) and P=0.30 for K(d)) in PFS patients (B(max)=901+/-83 fmol/mg protein, K(d)=0.682+/-0.046) and in matched controls (B(max)=1017+/-119 fmol/mg protein, K(d)=0.606+/-0.056). PRP 5-HT was significantly higher (P=0.0009) in PFS patients (955+/-101 ng/10(9) platelets) than in controls (633+/-50 ng/10(9) platelets). When adjusted for age, the levels of all CSF metabolites were lower in PFS patients. The CSF metabolite of norepinephrine (MHPG) was lower (P:=0.003) in PFS patients (8.33+/-0.33 ng/ml) than in matched controls (9.89+/-0.31 ng/ml) and 5-HIAA was lower (P=0.042) in PFS female patients (22.34+/-1.78 ng/ml) than in matched controls (25.75+/-1.75 ng/ml). For HVA in females, the difference between PFS patients (36.32+/-3.20 ng/ml) and matched controls (38.32+/-2.90 ng/ml) approached statistical significance (P=0.054).
Changes in metabolites of CSF biogenic amines appear to be partially correlated to age but remained diagnosis-dependent. High levels of PRP 5-HT in PFS patients were associated with low CSF 5-HIAA levels in female patients but were not accompanied by any change in serotonergic uptake as assessed by platelet [(3)H]imipramine binding sites. These findings do not allow us to confirm that serotonin metabolism is deregulated in PFS patients.
原发性纤维肌痛综合征(PFS)是一种在风湿病临床实践中常见的慢性疾病。1990年美国风湿病学会定义的该综合征的病理生理紊乱尚不清楚。本研究对30例患者进行评估,以验证PFS是一种由血清素代谢失调引起的疼痛调节障碍这一假说。
比较PFS患者富含血浆血小板(PRP)中的血小板[³H]丙咪嗪结合位点和血清素(5-HT)水平与匹配的健康对照者,并比较PFS患者脑脊液(CSF)中生物胺代谢产物水平与匹配对照者。
血小板[³H]丙咪嗪结合位点通过两个标准定义,即密度的B(max)和亲和力的K(d)。PRP中的5-HT以及CSF中的5-HT代谢产物(5-羟吲哚乙酸,5-HIAA)、去甲肾上腺素(3-甲氧基,4-羟基苯乙二醇,MHPG)和多巴胺(高香草酸,HVA)采用反相高效液相色谱法并通过库仑检测进行测定。
PFS患者(B(max)=901±83 fmol/mg蛋白,K(d)=0.682±0.046)和匹配对照者(B(max)=1017±119 fmol/mg蛋白,K(d)=0.606±0.056)的血小板[³H]丙咪嗪结合相似(B(max)的P=0.43,K(d)的P=0.30)。PFS患者(955±101 ng/10⁹血小板)的PRP 5-HT显著高于对照者(633±50 ng/10⁹血小板)(P=0.0009)。调整年龄后,PFS患者所有CSF代谢产物水平较低。PFS患者(8.33±0.33 ng/ml)的去甲肾上腺素CSF代谢产物(MHPG)低于匹配对照者(9.89±0.31 ng/ml)(P=0.003),PFS女性患者(22.34±1.78 ng/ml)的5-HIAA低于匹配对照者(25.75±1.75 ng/ml)(P=0.042)。对于女性患者的HVA,PFS患者(36.32±3.20 ng/ml)与匹配对照者(38.32±2.90 ng/ml)之间的差异接近统计学意义(P=0.054)。
CSF生物胺代谢产物的变化似乎部分与年龄相关,但仍依赖于诊断。PFS患者PRP 5-HT水平高与女性患者CSF 5-HIAA水平低相关,但如通过血小板[³H]丙咪嗪结合位点评估,血清素摄取未发生任何变化。这些发现不允许我们证实PFS患者血清素代谢失调。