Alpha 1 adrenoceptor expression in skin, nerves and blood vessels of patients with painful diabetic neuropathy

T. Schlereth; N. Morellini; N.C.A.M. Lismont; C. Lemper; F. Birklein; P.D. Drummond

doi:10.1016/j.autneu.2021.102814

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Alpha 1 adrenoceptor expression in skin, nerves and blood vessels of patients with painful diabetic neuropathy

Journal article

Open access

Peer reviewed

Alpha 1 adrenoceptor expression in skin, nerves and blood vessels of patients with painful diabetic neuropathy

T. Schlereth, N. Morellini, N.C.A.M. Lismont, C. Lemper, F. Birklein and P.D. Drummond

Autonomic Neuroscience: Basic and Clinical, Vol.234, Article 102814

2021

DOI: https://doi.org/10.1016/j.autneu.2021.102814

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Abstract

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.

Details

Title: Alpha 1 adrenoceptor expression in skin, nerves and blood vessels of patients with painful diabetic neuropathy
Authors/Creators: T. Schlereth (Author/Creator) - Johannes Gutenberg University Mainz
N. Morellini (Author/Creator) - Murdoch University
N.C.A.M. Lismont (Author/Creator) - Johannes Gutenberg University Mainz
C. Lemper (Author/Creator) - Johannes Gutenberg University Mainz
F. Birklein (Author/Creator) - Johannes Gutenberg University Mainz
P.D. Drummond (Author/Creator) - Murdoch University
Publication Details: Autonomic Neuroscience: Basic and Clinical, Vol.234, Article 102814
Publisher: Elsevier
Identifiers: 991005543173907891
Copyright: © 2021 Published by Elsevier B.V.
Murdoch Affiliation: School of Allied Health
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.253 Nerve Disorders; 1.253.1411 Diabetic Neuropathy
Web Of Science research areas: Neurosciences
ESI research areas: Neuroscience & Behavior