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. 2022 Jan 9;14(1):e21059.
doi: 10.7759/cureus.21059. eCollection 2022 Jan.

Association Between the Accumulation of Pentosidine at the Sciatic Nerve and Cutaneous Hindpaw Hypersensitivity in a Rat Ovariectomy Model

Tomotaka Umimura  1 , Yawara Eguchi  1 , Sumihisa Orita  1   2 , Kazuhide Inage  1 , Koki Abe  1 , Masahiro Inoue  1 , Hideyuki Kinoshita  1 , Masaki Norimoto  1 , Masashi Sato  1 , Takashi Sato  1 , Masahiro Suzuki  1 , Satoshi Maki  1   2 , Takeo Furuya  1 , Seiji Ohtori  1
Affiliations

Association Between the Accumulation of Pentosidine at the Sciatic Nerve and Cutaneous Hindpaw Hypersensitivity in a Rat Ovariectomy Model

Tomotaka Umimura et al. Cureus. .

Abstract

Introduction Advanced glycation end-products (AGEs) have the potential to serve as biomarkers of aging and metabolic diseases; however, how their expression relates to clinical symptoms is not well defined. In this study, we sought to determine whether the accumulation of pentosidine, one type of AGE, at the peripheral nerve is associated with cutaneous pain or hypersensitivity caused by ovariectomy (OVX). Methods We assigned 12-week-old female Sprague Dawley rats into either the OVX group (n = 6) or the sham group (n = 6). Cutaneous hindpaw sensitivity to mechanical stimuli was measured with von Frey filaments, using Chaplan's adapted method, and the 50% withdrawal threshold was calculated. Then, the accumulation of pentosidine, which represents AGEs, was measured in sciatic nerve fibers after staining with an anti-pentosidine antibody. Results OVX rats showed significantly increased plantar hypersensitivity to mechanical stimuli compared to sham rats 8 weeks after OVX (P = 0.017). Pentosidine-positive sciatic nerves were detected at a higher rate in OVX rats than in sham rats (P = 0.035). The pentosidine positivity rate in sciatic nerve fibers showed a negative correlation with withdrawal threshold (P < 0.001). Conclusions This study showed that higher levels of pentosidine in sciatic nerve fibers are associated with higher plantar hypersensitivity. Accumulation of pentosidine at the sciatic nerve, caused by OVX, may result in cutaneous hindpaw hypersensitivity.

Keywords: advanced glycation end-products; cutaneous; hypersensitivity; ovariectomy; pain; pentosidine; rats; sciatic nerve.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Hindpaw hypersensitivity using the von Frey test
The ovariectomy group (OVX) shows significantly increased plantar hypersensitivity to mechanical stimuli, as shown by the withdrawal threshold, compared to sham controls 8 weeks after ovariectomy (P = 0.017; Mann–Whitney U test).
Figure 2
Figure 2. Representative images of pentosidine staining of sciatic nerves from ovariectomized (OVX) and sham rats
Pentosidine staining (brown color) is visualized with the anti-pentosidine antibody (Arrows). (A, B) Brown pentosidine staining is shown by an increased accumulation of pentosidine in sciatic nerves of OVX rats. (C, D) The sciatic nerves of sham rats have fewer pentosidine-positive nerves than the OVX group.
Figure 3
Figure 3. Pentosidine positivity rate of sciatic nerve fibers
Pentosidine-positive sciatic nerves are observed significantly more frequently in ovariectomized (OVX) rats than in sham rats (P = 0.035; Mann–Whitney U test).
Figure 4
Figure 4. Relationship between withdrawal threshold and pentosidine positivity rate of sciatic nerve fibers
The pentosidine positivity rate of sciatic nerve fibers shows a negative correlation with the withdrawal threshold (P < 0.001).
See this image and copyright information in PMC

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