DKD Helios Klinik Wiesbaden, Department of Neurology, Aukammallee 33, 65191 Wiesbaden, Germany; University Medical Centre of the Johannes Gutenberg-University Mainz, Department of Neurology, Langenbeckstrasse 1, 55131 Mainz, Germany.
College of Science, Health, Engineering and Education, Murdoch University, Perth, Western Australia, Australia.
Auton Neurosci. 2021 Sep;234:102814. doi: 10.1016/j.autneu.2021.102814. Epub 2021 May 3.
Diabetic neuropathy (dNP) patients often suffer from severe neuropathic pain. It was suggested that alpha-1 adrenoceptor (α-AR) hyperresponsiveness contributes to pain in dNP. The aim of our study was to quantify α-AR expression using immunohistochemistry in skin biopsies of nine patients with painful diabetic neuropathy compared to 10 healthy controls. Additionally, the association between α-AR expression and activation with spontaneous and sympathetically maintained pain (SMP) induced by intradermal injection of the α-agonist phenylephrine was investigated. For control purposes the α-agonist clonidine was injected in a different session. We found that dermal nerve density was significantly lower in dNP than in controls. However, α-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 α-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 α-upregulation should be examined in further studies.
糖尿病性神经病变（dNP）患者常患有严重的神经病理性疼痛。有研究提示，α1 肾上腺素能受体（α-AR）的高反应性与 dNP 疼痛有关。我们的研究目的是使用免疫组织化学方法，定量检测 9 例伴有痛性糖尿病神经病变患者和 10 例健康对照者皮肤活检标本中的α-AR 表达。此外，还研究了 α-AR 表达和激活与皮内注射 α-激动剂苯肾上腺素引起的自发性和交感维持性疼痛（SMP）之间的关系。为了控制目的，在不同的时段内注射了 α-激动剂可乐定。我们发现，与对照组相比，dNP 患者的皮肤神经密度显著降低。然而，dNP 患者的皮肤血管和角质形成细胞上的 α-AR 表达明显高于对照组。皮肤神经也观察到类似的趋势，但未达到显著水平。皮内注射苯肾上腺素仅引起轻微疼痛，几分钟后即可缓解。在仅 1 例患者中，肾上腺素能诱发的疼痛持续超过 15 分钟，但没有患者符合 SMP 的标准（注射苯肾上腺素后疼痛增加，注射可乐定后疼痛减少）。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-AR 的高表达是一个重要的发现，因为这可能导致 dNP 的进展，并支持去神经结构的受体上调理论。应该在进一步的研究中检查这种 α-上调的意义。
