Increased miR-132-3p expression is associated with chronic neuropathic pain.
Increased miR-132-3p expression is associated with chronic neuropathic pain.
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DOI：
10.1016/j.expneurol.2016.06.025
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发表时间：
2016-09
影响因子：
5.3
通讯作者：
Sorkin LS
中科院分区：
文献类型：
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作者：
Leinders M;Üçeyler N;Pritchard RA;Sommer C;Sorkin LS
神经免疫平衡的改变在慢性神经病理性疼痛的病理生理学中起主要作用。microRNA（miRNA）可以调节免疫和神经过程，并且可以作为慢性疼痛发展和维持的主开关。我们开始分析miR-132- 3 p的作用，首先在周围神经病患者中，其次在神经性疼痛动物模型中。我们首先通过测量30名患者和30名健康对照的白色血细胞（WBC）中的miR-132- 3 p水平来确定其表达，然后基于临床诊断在81名患有疼痛或无痛炎性或非炎性神经病变的患者的腓肠神经活检中确定其表达。我们发现与健康对照相比，神经病患者的WBC中miR-132- 3 p表达增加2.6倍（p<0.001）。与没有疼痛的那些相比，在来自患有神经性疼痛的神经病患者的腓肠神经活检中，miR-132- 3 p表达也略微上调（1.2倍; p<0.001）。这些有希望的发现在神经病理性疼痛的动物模型，备用神经损伤模型（SNI）中进一步研究。为此目的，在大鼠的背根神经节和脊髓中测量miR-132- 3 p表达水平。随后，用miRNA拮抗剂或模拟物对miR-132- 3 p表达进行间接调节，并评估诱发的疼痛和疼痛厌恶。脊髓miR-132- 3 p水平在SNI后10天最高，这是建立持续性异常性疼痛的时间（p<0.05）。通过鞘内（i.t.）导管剂量依赖性地逆转了机械性异常性疼痛（P<0.001），并消除了位置逃避回避范式中的疼痛行为（P<0.001）。鞘内注射miR-132- 3 p模拟物可剂量依赖性地诱导幼稚大鼠的疼痛行为（p<0.001）。总之，这些结果表明miR-132- 3 p在慢性神经性疼痛中的促伤害感受作用。
Alterations in the neuro-immune balance play a major role in the pathophysiology of chronic neuropathic pain. MicroRNAs (miRNA) can regulate both immune and neuronal processes and may function as master switches in chronic pain development and maintenance. We set out to analyze the role of miR-132-3p, first in patients with peripheral neuropathies and second in an animal model of neuropathic pain. We initially determined miR-132-3p expression by measuring its levels in white blood cells (WBC) of 30 patients and 30 healthy controls and next in sural nerve biopsies of 81 patients with painful or painless inflammatory or non-inflammatory neuropathies based on clinical diagnosis. We found a 2.6 fold increase in miR-132-3p expression in WBC of neuropathy patients compared to healthy controls (p<0.001). MiR-132-3p expression was also slightly up-regulated in sural nerve biopsies from neuropathy patients suffering from neuropathic pain compared to those without pain (1.2 fold; p<0.001). These promising findings were investigated further in an animal model of neuropathic pain, the spared nerve injury model (SNI). For this purpose miR-132-3p expression levels were measured in dorsal root ganglia and spinal cord of rats. Subsequently, miR-132-3p expression was pharmacologically modulated with miRNA antagonists or mimetics, and evoked pain and pain aversion were assessed. Spinal miR-132-3p levels were highest 10 days after SNI, a time when persistent allodynia was established (p<0.05). Spinal administration of miR-132-3p antagonists via intrathecal (i.t.) catheters dose dependently reversed mechanical allodyina (p<0.001) and eliminated pain behavior in the place escape avoidance paradigm (p<0.001). Intrathecal administration of miR-132-3p mimetic dose-dependently induced pain behavior in naïve rats (p<0.001). Taken together these results indicate a pro-nociceptive effect of miR-132-3p in chronic neuropathic pain.