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Alpha 1 adrenoceptor expression in skin, nerves and blood vessels of patients with painful diabetic neuropathy
Autonomic Neuroscience ( IF 2.7 ) Pub Date : 2021-05-03 , DOI: 10.1016/j.autneu.2021.102814
Tanja Schlereth 1 , Natalie Morellini 2 , Noémie C A M Lismont 3 , Cassandra Lemper 3 , Frank Birklein 3 , Peter D Drummond 2
Affiliation  

Diabetic neuropathy (dNP) patients often suffer from severe neuropathic pain. It was suggested that alpha-1 adrenoceptor (α1-AR) hyperresponsiveness contributes to pain in dNP. The aim of our study was to quantify α1-AR expression using immunohistochemistry in skin biopsies of nine patients with painful diabetic neuropathy compared to 10 healthy controls. Additionally, the association between α1-AR expression and activation with spontaneous and sympathetically maintained pain (SMP) induced by intradermal injection of the α1-agonist phenylephrine was investigated. For control purposes the α2-agonist clonidine was injected in a different session.

We found that dermal nerve density was significantly lower in dNP than in controls. However, α1-AR expression was significantly greater on cutaneous blood vessels and keratinocytes of dNP patients than controls. A similar trend, which failed to reach significance, was observed for dermal nerves. Intradermal injection of phenylephrine induced only minor pain, which resolved after a few minutes. Adrenergically evoked pain persisted for more than 15 min in only one patient, but none of the patients fulfilled the criteria for SMP (pain increase after injection of phenylephrine and decrease after clonidine).

In conclusion, our results imply that SMP does not occur in dNP. However, elevated expression of α1-AR on keratinocytes and dermal blood vessels is an important finding, since this could contribute to dNP progression and supports the theory of receptor up-regulation of denervated structures. The implications of this α1-upregulation should be examined in further studies.



中文翻译:

疼痛性糖尿病神经病变患者皮肤、神经和血管中 Alpha 1 肾上腺素能受体的表达

糖尿病性神经病变 (dNP) 患者经常遭受严重的神经性疼痛。有人提出 α1 肾上腺素能受体 (α 1 -AR) 高反应性导致 dNP 疼痛。我们研究的目的是使用免疫组织化学对 9 名患有疼痛性糖尿病神经病变的患者与 10 名健康对照者的皮肤活检中的 α 1 -AR 表达进行量化。此外,研究了 α 1 -AR 表达和激活与皮内注射 α 1 -激动剂去氧肾上腺素诱导的自发性和交感神经维持性疼痛 (SMP)之间的关联。为了对照目的,α 2 -激动剂可乐定在不同的疗程中注射。

我们发现 dNP 中的真皮神经密度明显低于对照组。然而,dNP患者的皮肤血管和角质形成细胞上的α 1 -AR表达显着高于对照组。在真皮神经中观察到了类似的趋势,但未能达到显着性。去氧肾上腺素皮内注射仅引起轻微疼痛,几分钟后缓解。只有一名患者的肾上腺素诱发的疼痛持续超过 15 分钟,但没有一名患者符合 SMP 的标准(注射去氧肾上腺素后疼痛增加,可乐定后疼痛减轻)。

总之,我们的结果表明 SMP 不会发生在 dNP 中。然而,角质形成细胞和真皮血管上α 1 -AR 的表达升高是一个重要发现,因为这可能有助于 dNP 进展并支持去神经结构受体上调的理论。这种 α 1 -上调的含义应在进一步的研究中进行检查。

更新日期:2021-05-05
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