Silva M, Martins D, Charrua A, Piscitelli F, Tavares I, Morgado C, Di Marzo V
Departamento de Biologia Experimental, Faculdade de Medicina, Universidade do Porto, Portugal; I3S - Instituto de Inovação e investigação em Saúde, Universidade do Porto, Portugal.
I3S - Instituto de Inovação e investigação em Saúde, Universidade do Porto, Portugal; Departmento de Doenças Renais, Urológicas e Infecciosas, Faculdade de Medicina, Universidade do Porto, Portugal.
Neuropharmacology. 2016 Aug;107:49-57. doi: 10.1016/j.neuropharm.2016.03.007. Epub 2016 Mar 8.
The involvement of transient receptor vanilloid type-1 (TRPV1) channels in pain modulation by the brain remains understudied. The rostroventromedial medulla (RVM) plays a key role in conveying to the spinal cord pain modulatory influences triggered in higher brain centres, with co-existence of inhibitory (antinociceptive) and facilitatory (pronociceptive) effects. In spite of some reports of TRPV1 expression in the RVM, it remains unknown if endovanilloid signalling plays a direct role in local pain modulation. Here we used a model of diabetic neuropathy, the streptozotocin (STZ)-diabetic rat, to study the role of endovanilloid signalling in RVM-mediated pain modulation during chronic pain. Four weeks after diabetes induction, the levels of TRPV1 mRNA and fatty acid amide hydrolase (FAAH), a crucial enzyme for endovanilloid catabolism, in the RVM of STZ-diabetic rats were higher than control. The RVM of STZ-diabetic rats presented decreased levels of several TRPV1 endogenous ligands, namely anandamide (AEA), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). Administration of capsaicin (a TRPV1 agonist) into the RVM decreased nociceptive behavioural responses in the inflammatory phase of the formalin test (phase 2). These findings suggest that diabetic neuropathy induces plastic changes of RVM endovanilloid signalling, indicating that TRPV1 may be a putative target for pain modulation in this chronic pain condition.
瞬时受体香草酸亚型1（TRPV1）通道在大脑疼痛调节中的作用仍未得到充分研究。延髓头端腹内侧区（RVM）在将高级脑中枢触发的疼痛调节影响传递至脊髓方面起着关键作用，同时存在抑制性（抗伤害感受性）和易化性（促伤害感受性）作用。尽管有一些关于RVM中TRPV1表达的报道，但内源性香草酸信号是否在局部疼痛调节中起直接作用仍不清楚。在这里，我们使用糖尿病性神经病变模型——链脲佐菌素（STZ）诱导的糖尿病大鼠，来研究内源性香草酸信号在慢性疼痛期间RVM介导的疼痛调节中的作用。糖尿病诱导四周后，STZ糖尿病大鼠RVM中TRPV1 mRNA和脂肪酸酰胺水解酶（FAAH，内源性香草酸分解代谢的关键酶）的水平高于对照组。STZ糖尿病大鼠的RVM中几种TRPV1内源性配体的水平降低，即花生四烯酸乙醇胺（AEA）、棕榈酰乙醇胺（PEA）和油酰乙醇胺（OEA）。向RVM注射辣椒素（一种TRPV1激动剂）可降低福尔马林试验炎症期（第2期）的伤害性行为反应。这些发现表明，糖尿病性神经病变会诱导RVM内源性香草酸信号的可塑性变化，表明TRPV1可能是这种慢性疼痛状态下疼痛调节的一个假定靶点。
