Acid-sensing ion channel 3 expression in mouse knee joint afferents and effects of carrageenan-induced arthritis

Masahiko Ikeuchi; Sandra J Kolker; Kathleen A Sluka

doi:10.1016/j.jpain.2008.10.010

Back

Acid-sensing ion channel 3 expression in mouse knee joint afferents and effects of carrageenan-induced arthritis

Journal article

Open access

Peer reviewed

Acid-sensing ion channel 3 expression in mouse knee joint afferents and effects of carrageenan-induced arthritis

Masahiko Ikeuchi, Sandra J Kolker and Kathleen A Sluka

The journal of pain, Vol.10(3), pp.336-342

03/2009

DOI: 10.1016/j.jpain.2008.10.010

PMCID: PMC2675631

PMID: 19185546

Files and links (1)

url

https://doi.org/10.1016/j.jpain.2008.10.010View

Published (Version of record) Open Access

Abstract

Arthritis is associated with decreases in local pH. Of the acid-sensing ion channels (ASIC), ASIC3 is most sensitive to such a pH change, abundantly expressed in dorsal root ganglion (DRG), and critical for the development of secondary hyperalgesia. The purpose of this study was to investigate the upregulation of ASIC3, using an acute arthritic pain model in mice. We examined ASIC3 expression in DRG neurons innervating the knee joint with and without carrageenan-induced arthritis by means of retrograde labeling and immunohistochemistry. We also examined the difference of DRG phenotype between ASIC3+/+ and ASIC3-/- mice. ASIC3 immunoreactivity was present in 31% of knee joint afferents and dominantly in small cells. After joint inflammation, ASIC3-immunoreactive neurons significantly increased in number by 50%. Calcitonin gene-related peptide (CGRP) increased similarly in both ASIC3+/+ and ASIC3-/- mice. Soma size distribution of ASIC3-immunoreactive neurons without CGRP expression was shifted to smaller-diameter neurons. Our results suggest that ASIC3 plays an important role in acute arthritic pain. Specifically, we propose that ASIC3 upregulation along with CGRP and phenotypic change in ASIC3-immunoreactive neurons without CGRP are responsible for the development of secondary hyperalgesia after carrageenan-induced arthritis. This article shows that ASIC3 is upregulated along with CGRP in knee joint afferents and that there is a phenotypic change in ASIC3-immunoreactive nonpeptidergic neurons in an animal model of acute arthritis. Understanding the basic neurobiology after acute arthritis could lead to future new pharmacological management of arthritis.

Immunohistochemistry

Up-Regulation

Arthritis - physiopathology

Arthritis - metabolism

Gene Expression - genetics

Knee Joint - physiopathology

Pain - metabolism

Knee Joint - innervation

Arthritis - chemically induced

Sodium Channels - metabolism

Pain - etiology

Calcitonin Gene-Related Peptide - metabolism

Disease Models, Animal

Acute Disease

Acid Sensing Ion Channels

Mice, Inbred C57BL

Mice, Knockout

Animals

Analysis of Variance

Pain - physiopathology

Mice

Sodium Channels - genetics

Carrageenan

Neurons, Afferent - metabolism

Ganglia, Spinal - metabolism

Details

Title: Subtitle: Acid-sensing ion channel 3 expression in mouse knee joint afferents and effects of carrageenan-induced arthritis
Creators: Masahiko Ikeuchi - Physical Therapy and Rehabilitation Science Graduate Program, Pain Research Program, University of Iowa, Iowa City, Iowa, USA. ikeuchim@kochi-u.ac.jp
Sandra J Kolker
Kathleen A Sluka
Resource Type: Journal article
Publication Details: The journal of pain, Vol.10(3), pp.336-342
DOI: 10.1016/j.jpain.2008.10.010
PMID: 19185546
PMCID: PMC2675631
NLM abbreviation: J Pain
ISSN: 1526-5900
eISSN: 1528-8447
Publisher: United States
Grant note: AR053509 / NIAMS NIH HHS R01 AR053509-01A1 / NIAMS NIH HHS R01 AR053509 / NIAMS NIH HHS
Language: English
Date published: 03/2009
Academic Unit: Iowa Neuroscience Institute; Nursing; Anesthesia; Physical Therapy and Rehabilitation Science; Neuroscience and Pharmacology
Record Identifier: 9984040343702771

Metrics

31 Record Views

83 Times Cited - Web of Science