Klein Caroline P, Sperotto Nathalia D M, Maciel Izaque S, Leite Carlos E, Souza Alessandra H, Campos Maria M
Postgraduate Program in Cellular and Molecular Biology, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Faculty of Pharmacy, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Neuropharmacology. 2014 Nov;86:57-66. doi: 10.1016/j.neuropharm.2014.05.043. Epub 2014 Jun 11.
This study investigated whether the spinal or systemic treatment with the lipid resolution mediators resolvin D1 (RvD1), aspirin-triggered resolvin D1 (AT-RvD1) and resolvin D2 (RvD2) might interfere with behavioral and neurochemical changes in the mouse fibromyalgia-like model induced by reserpine. Acute administration of AT-RvD1 and RvD2 produced a significant inhibition of mechanical allodynia and thermal sensitization in reserpine-treated mice, whereas RvD1 was devoid of effects. A similar antinociceptive effect was obtained by acutely treating animals with the reference drug pregabalin. Noteworthy, the repeated administration of AT-RvD1 and RvD2 also prevented the depressive-like behavior in reserpine-treated animals, according to assessment of immobility time, although the chronic administration of pregabalin failed to affect this parameter. The induction of fibromyalgia by reserpine triggered a marked decrease of dopamine and serotonin (5-HT) levels, as examined in total brain, spinal cord, cortex and thalamus. Reserpine also elicited a reduction of glutamate levels in total brain, and a significant increase in the spinal cord and thalamus. Chronic treatment with RvD2 prevented 5-HT reduction in total brain, and reversed the glutamate increases in total brain and spinal cord. Otherwise, AT-RvD1 led to a recovery of dopamine levels in cortex, and 5-HT in thalamus, whilst it diminished brain glutamate contents. Concerning pregabalin, this drug prevented dopamine reduction in total brain, and inhibited glutamate increase in brain and spinal cord of reserpine-treated animals. Our data provide novel evidence, showing the ability of D-series resolvins AT-RvD1, and mainly RvD2, in reducing painful and depressive symptoms allied to fibromyalgia in mice.
本研究调查了用脂质消退介质消退素D1（RvD1）、阿司匹林触发的消退素D1（AT-RvD1）和消退素D2（RvD2）进行脊髓或全身治疗是否会干扰利血平诱导的小鼠纤维肌痛样模型中的行为和神经化学变化。急性给予AT-RvD1和RvD2可显著抑制利血平处理小鼠的机械性异常性疼痛和热敏化，而RvD1则无此作用。用参比药物普瑞巴林急性处理动物也获得了类似的抗伤害感受作用。值得注意的是，根据不动时间评估，重复给予AT-RvD1和RvD2还可预防利血平处理动物的抑郁样行为，尽管长期给予普瑞巴林未能影响该参数。如在全脑、脊髓、皮质和丘脑中检测到的，利血平诱导纤维肌痛会引发多巴胺和5-羟色胺（5-HT）水平显著降低。利血平还导致全脑中谷氨酸水平降低，以及脊髓和丘脑中谷氨酸水平显著升高。用RvD2进行慢性治疗可防止全脑中5-HT水平降低，并逆转全脑和脊髓中谷氨酸水平的升高。否则，AT-RvD1可使皮质中的多巴胺水平和丘脑中的5-HT水平恢复，同时降低脑内谷氨酸含量。关于普瑞巴林，该药物可防止全脑中多巴胺水平降低，并抑制利血平处理动物脑和脊髓中谷氨酸水平的升高。我们的数据提供了新的证据，表明D系列消退素AT-RvD1，主要是RvD2，具有减轻小鼠纤维肌痛相关疼痛和抑郁症状的能力。
