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BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2011

Open Access 01-12-2011 | Research article

Pain-related sensory innervation in monoiodoacetate-induced osteoarthritis in rat knees that gradually develops neuronal injury in addition to inflammatory pain

Authors: Sumihisa Orita, Tetsuhiro Ishikawa, Masayuki Miyagi, Nobuyasu Ochiai, Gen Inoue, Yawara Eguchi, Hiroto Kamoda, Gen Arai, Tomoaki Toyone, Yasuchika Aoki, Takekazu Kubo, Kazuhisa Takahashi, Seiji Ohtori

Published in: BMC Musculoskeletal Disorders | Issue 1/2011

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Abstract

Background

The exact mechanism of knee osteoarthritis (OA)-associated pain is unclear, whereas mixed evidence of inflammatory pain and neuropathic pain has been noted. We aimed to investigate pain-related sensory innervation in a monoiodoacetate (MIA)-induced model of OA.

Methods

Sixty of seventy female Sprague Dawley rats of six week-old underwent intra-articular MIA and fluorogold (FG) retrograde neurotracer injection into their right (ipsilateral) knee, while their left knees were treated with FG in saline as a control (contralateral knee). Other rats were treated with FG only bilaterally, and used as controls. Rats were evaluated for tactile allodynia using von Frey hairs. Proinflammatory mediators in the knee soft tissues, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and nerve growth factor (NGF), were quantified using ELISAs to evaluate inflammation in the knee after 1, 4, 7,14,21, and 28 days post injection:. Dorsal root ganglia (DRG) were immunostained for three molecules after 7,14,21, and 28 days post injection: calcitonin gene-related peptide (CGRP), a marker of inflammatory pain; and activating transcription factor-3 (ATF3) and growth associated protein-43 (GAP43), as markers for nerve injury and regenerating axons. The distribution of microglia in the spinal cord were also evaluated, because they have been reported to increase in neuropathic pain states. These evaluations were performed up to 28 days postinjection. P < 0.05 was considered significant.

Results

Progressive tactile allodynia and elevated cytokine concentrations were observed in ipsilateral knees. CGRP-immunoreactive (-ir) ipsilateral DRG neurons significantly increased, peaking at 14 days postinjection, while expression of FG-labeled ATF3-ir or ATF3-ir GAP43-ir DRG neurons significantly increased in a time-dependent manner. Significant proliferation of microglia were found with time in the ipsilateral dorsal horn.

Conclusions

Pain-related characteristics in a MIA-induced rat OA model can originate from an inflammatory pain state induced by the local inflammation initiated by inflammatory cytokines, and that state will be followed by gradual initiation of neuronal injury, which may induce the neuropathic pain state.
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Metadata
Title
Pain-related sensory innervation in monoiodoacetate-induced osteoarthritis in rat knees that gradually develops neuronal injury in addition to inflammatory pain
Authors
Sumihisa Orita
Tetsuhiro Ishikawa
Masayuki Miyagi
Nobuyasu Ochiai
Gen Inoue
Yawara Eguchi
Hiroto Kamoda
Gen Arai
Tomoaki Toyone
Yasuchika Aoki
Takekazu Kubo
Kazuhisa Takahashi
Seiji Ohtori
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2011
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/1471-2474-12-134

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