实验性疼痛性糖尿病周围神经病变的常规、高频和差异靶向多路脊髓刺激:疼痛行为和中枢炎症平衡的作用。

IF 2.8 3区 医学 Q2 NEUROSCIENCES
Thomas J de Geus, Glenn Franken, Elbert A Joosten
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引用次数: 1

摘要

脊髓刺激(SCS)是缓解疼痛的糖尿病周围神经病变(PDPN)患者疼痛的最后手段。然而,SCS在PDPN中的有效性是有限的。新的脊髓刺激范例,如高频(HF)和差异靶点复用(DTM),可能会提高PDPN患者脊髓刺激镇痛的反应率和疗效,并被认为可以调节脊髓背角的炎症平衡和神经胶质反应。本研究的目的是在PDPN动物模型中研究Con-、HF-和DTM-SCS对疼痛行为和脊髓炎症平衡的影响。链脲佐菌素诱导的PDPN动物用Con-SCS(50Hz)、HF-SCS(1200Hz)或DTM-SCS(Con-和HF-SCS的组合)刺激48小时。使用Von Frey(VF)测试评估机械超敏反应,并使用机械冲突回避系统(MCAS)评估疼痛的动机方面。基于促炎和抗炎细胞因子(Tnf-α,Il-1ß,Il-4,Il-10)、小胶质细胞标记物(Itgam)、星形胶质细胞标记(Gfap)、T细胞标记物、小胶质增殖标记物(Irf8,Adgre1)和P2X4、p13 MAPK、BDNF信号标记物(P2X4,Mapk14,BDNF)的RNA表达,分析脊髓背侧的炎症平衡和神经胶质反应。结果表明,在PDPN动物中,与Sham-SCS相比,Con-、HF-和DTM-SCS在刺激48小时后显著降低了超敏反应,但同时不影响MCAS中的逃逸潜伏期。在分子水平上,与DTM-SCS和Sham-SCS相比,Con-SCS导致48小时后脊髓促炎细胞因子Tnf-α显著增加。总之,Con-SCS显示炎症平衡向促炎状态转变,而HF和DTM-SCS则将平衡向抗炎状态转变。这些发现表明,Con-SCS诱导PDPN疼痛缓解的潜在机制与HF和DTM-SCS诱导的不同。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Conventional, high frequency and differential targeted multiplexed spinal cord stimulation in experimental painful diabetic peripheral neuropathy: Pain behavior and role of the central inflammatory balance.

Conventional, high frequency and differential targeted multiplexed spinal cord stimulation in experimental painful diabetic peripheral neuropathy: Pain behavior and role of the central inflammatory balance.

Conventional, high frequency and differential targeted multiplexed spinal cord stimulation in experimental painful diabetic peripheral neuropathy: Pain behavior and role of the central inflammatory balance.

Conventional, high frequency and differential targeted multiplexed spinal cord stimulation in experimental painful diabetic peripheral neuropathy: Pain behavior and role of the central inflammatory balance.

Spinal cord stimulation (SCS) is a last resort treatment for pain relief in painful diabetic peripheral neuropathy (PDPN) patients. However, the effectivity of SCS in PDPN is limited. New SCS paradigms such as high frequency (HF) and differential target multiplexed (DTM) might improve responder rates and efficacy of SCS-induced analgesia in PDPN patients, and are suggested to modulate the inflammatory balance and glial response in the spinal dorsal horn. The aim of this study was to research the effects of Con-, HF- and DTM-SCS on pain behavior and the spinal inflammatory balance in an animal model of PDPN. Streptozotocin-induced PDPN animals were stimulated for 48 hours with either Con-SCS (50Hz), HF-SCS (1200Hz) or DTM-SCS (combination of Con- and HF-SCS). Mechanical hypersensitivity was assessed using Von Frey (VF) test and the motivational aspects of pain were assessed using the mechanical conflict avoidance system (MCAS). The inflammatory balance and glial response were analyzed in the dorsal spinal cord based on RNA expression of pro- and anti-inflammatory cytokines (Tnf-α, Il-1ß, Il-4, Il-10), a microglia marker (Itgam), an astrocyte marker (Gfap), a T-cell marker (Cd3d), microglia proliferation markers (Irf8, Adgre1) and P2X4, p13-MAPK, BDNF signaling markers (P2x4, Mapk14, Bdnf). The results show that Con-, HF-, and DTM-SCS significantly decreased hypersensitivity after 48 hours of stimulation compared to Sham-SCS in PDPN animals, but at the same time did not affect escape latency in the MCAS. At the molecular level, Con-SCS resulted in a significant increase in spinal pro-inflammatory cytokine Tnf-α after 48 hours compared to DTM-SCS and Sham-SCS. In summary, Con-SCS showed a shift of the inflammatory balance towards a pro-inflammatory state whilst HF- and DTM-SCS shifted the balance towards an anti-inflammatory state. These findings suggest that the underlying mechanism of Con-SCS induced pain relief in PDPN differs from that induced by HF- and DTM-SCS.

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来源期刊
Molecular Pain
Molecular Pain 医学-神经科学
CiteScore
5.60
自引率
3.00%
发文量
56
审稿时长
6-12 weeks
期刊介绍: Molecular Pain is a peer-reviewed, open access journal that considers manuscripts in pain research at the cellular, subcellular and molecular levels. Molecular Pain provides a forum for molecular pain scientists to communicate their research findings in a targeted manner to others in this important and growing field.
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