Analysis of Macrophages and Peptidergic Fibers in the Skin of Patients With Painful Diabetic Polyneuropathy. Issue 1 (11th January 2022)

• Record Type: Journal Article
• Authors: Gylfadottir, Sandra Sif; Itani, Mustapha; Kristensen, Alexander Gramm; Tankisi, Hatice; Jensen, Troels Staehelin; Sindrup, Søren H.; Bennett, David; Nyengaard, Jens Randel; Finnerup, Nanna Brix; Karlsson, Pall
• Is Part Of: Neurology. Volume 9:Issue 1(2022)
• Publication Date: 2022-01-11
• Subjects: Neuroimmunology -- Periodicals; Neurology -- Periodicals; 616.8
• DOI: 10.1212/NXI.0000000000001111
• Languages: English
• ISSNs: 2332-7812

Abstract

Abstract : Background and Objectives: The mechanisms of pain in patients with diabetic polyneuropathy are unknown. Studies have suggested a role of inflammation and increased neuropeptides peripherally in pain generation. This study examined the possible skin markers of painful diabetic polyneuropathy (P-DPN): macrophages, substance P (SP), and calcitonin gene-related peptide (CGRP). Methods: The participants were included from a large Danish cross-sectional clinical study of type 2 diabetes. We diagnosed definite diabetic polyneuropathy using the Toronto criteria and used the Neuropathic Pain Special Interest Group classification for defining P-DPN. We included 60 skin biopsies from patients with diabetic polyneuropathy—30 with P-DPN and 30 with nonpainful diabetic polyneuropathy (NP-DPN)—and 30 biopsies from healthy controls of similar age and sex. The biopsies were stained using PGP 9.5, IbA1, and SP and CGRP primary markers. Results: There was increased macrophage density in patients with P-DPN (8.0%) compared with that in patients with NP-DPN (5.1%, p < 0.001), and there was increased macrophage density in patients with NP-DPN (5.1%) compared with that in healthy controls (3.1%, p < 0.001). When controlling for neuropathy severity, body mass index, age, and sex, there was still a difference in macrophage density between patients with P-DPN and patients with NP-DPN. Patients with P-DPN had higher median nerve fiber length density (274.5 and 155 mm −2 for SP and CGRP, respectively) compared with patients with NP-DPN (176 and 121 mm −2 for SP and CGRP, respectively, p = 0.009 and 0.04) and healthy controls (185.5 and 121.5 mm −2 for SP and CGRP, respectively), whereas there was no difference between patients with NP-DPN and controls without diabetes ( p = 0.64 and 0.49, respectively). The difference between P-DPN and NP-DPN for SP and CGRP was significant only in female patients, although a trend was seen in male patients. Discussion: The findings point to a possible involvement of the innate immune system in the pathogenesis of neuropathic pain in patients with DPN, although markers of activated macrophages were not measured in this study.