Miclescu Adriana A, Svahn Martin, Gordh Torsten E
Multidisciplinary Pain Clinic, Uppsala University Hospital, Uppsala, Sweden.
Multidisciplinary Pain Clinic, Uppsala University Hospital, Uppsala, Sweden ; Pain Research, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
J Pain Res. 2015 Jul 15;8:387-97. doi: 10.2147/JPR.S84685. eCollection 2015.
This study was carried out in patients with neuropathic pain in order to assess the analgesic effects and changes in protein biomarkers after the administration of methylene blue (MB), a diaminophenothiazine with antioxidant and anti-inflammatory properties, and with inhibitory effects on nitric oxide.
Ten patients with chronic refractory neuropathic pain were randomized to receive either MB (10 mg/mL Methylthioninium chloride) 2 mg/kg (MB group) or MB 0.02 mg/kg (control group) infused over 60 minutes. Sensory function and pain (Numerical Rating Scale) were evaluated at baseline and at 60 minutes after the start of the infusion. The patients kept a pain diary during the next 24 hours and for the following 4 days. Plasma and urinary concentrations of 8-isoprostane-prostaglandin F2α (8-iso-PGF2α) and plasma protein biomarkers prior to and after the infusions were measured with radioimmunoassay and with proximity extension assay.
A decrease of the Numerical Rating Scale at 60 minutes in comparison with baseline was observed in the MB (P=0.047) group. The decrease was significant between the MB and the control group on the day of and day after MB infusion (P=0.04 and P=0.008, respectively). There was no difference in systemic protein expressions between groups except for prolactin (PRL) (P=0.02). Three patients demonstrated diminished dynamic mechanical allodynia.
MB decreased the pain levels in patients with chronic therapy-resistant neuropathic pain on the first 2 days after administration. Known as an endocrine modulator on the anterior pituitary gland, MB infusion produced a decrease of PRL. The detailed role of PRL effects in chronic neuropathic pain remains undetermined.
本研究针对神经性疼痛患者开展，旨在评估亚甲蓝（MB）给药后的镇痛效果及蛋白质生物标志物变化。亚甲蓝是一种具有抗氧化、抗炎特性且对一氧化氮有抑制作用的二氨基吩噻嗪。
10例慢性难治性神经性疼痛患者被随机分为两组，分别接受60分钟内输注2mg/kg的MB（10mg/mL亚甲蓝氯）（MB组）或0.02mg/kg的MB（对照组）。在输注开始前及开始后60分钟评估感觉功能和疼痛程度（数字评分量表）。患者在接下来的24小时及随后4天记录疼痛日记。采用放射免疫分析法和邻近延伸分析法测量输注前后血浆和尿液中8-异前列腺素F2α（8-iso-PGF2α）的浓度以及血浆蛋白质生物标志物。
MB组在输注60分钟时数字评分量表较基线有所下降（P = 0.047）。在MB输注当天及输注后一天，MB组与对照组之间的下降差异显著（分别为P = 0.04和P = 0.008）。除催乳素（PRL）外（P = 0.02），两组间全身蛋白质表达无差异。3例患者的动态机械性异常性疼痛减轻。
MB在给药后的头两天降低了慢性治疗抵抗性神经性疼痛患者的疼痛水平。作为一种对垂体前叶的内分泌调节剂，MB输注导致PRL降低。PRL在慢性神经性疼痛中的具体作用仍未确定。
