Journal article
ASIC1 and ASIC3 Play Different Roles in the Development of Hyperalgesia After Inflammatory Muscle Injury
The journal of pain, Vol.11(3), pp.210-218
2010
DOI: 10.1016/j.jpain.2009.07.004
PMID: 20015700
Abstract
Acid-sensing ion channels (ASICs) respond to acidosis that normally occurs after inflammation. We examined the expression of
ASIC1,
ASIC2, and
ASIC3 mRNAs in lumbar dorsal root ganglion neurons before and 24 hours after carrageenan-induced muscle inflammation. Muscle inflammation causes bilateral increases of
ASIC2 and
ASIC3 but not
ASIC1 (neither
ASIC1a nor
ASIC1b) mRNA, suggesting differential regulation of
ASIC1 versus
ASIC2 and
ASIC3 mRNA. Similar mRNA increases were observed after inflammation in knockout mice:
ASIC2 mRNA increases in
ASIC3-/- mice;
ASIC2 and
ASIC3 mRNAs increase in
ASIC1-/- mice. Prior behavioral studies in
ASIC3-/- mice showed deficits in secondary hyperalgesia (increased response to noxious stimuli outside the site of injury) but not primary hyperalgesia (increased response to noxious stimuli at the site of injury). In this study, we show that
ASIC1-/- mice do not develop primary muscle hyperalgesia but develop secondary paw hyperalgesia. In contrast, and as expected,
ASIC3-/- mice develop primary muscle hyperalgesia but do not develop secondary paw hyperalgesia. The pharmacological utility of the nonselective ASIC inhibitor A-317567, given locally, was tested. A-317567 reverses both the primary and the secondary hyperalgesia induced by carrageenan muscle inflammation. Thus, peripherally located ASIC1 and ASIC3 play different roles in the development of hyperalgesia after muscle inflammation.
This study shows changes in ASIC mRNA expression and behavioral hyperalgesia of C57Bl/6 (wild type), ASIC1-/-, and ASIC3-/- mice before and after the induction of muscle inflammation. A-317567 was effective in reversing hyperalgesia in these animals, suggesting the potential of ASICs as therapeutic targets for muscle inflammatory pain.
Details
- Title: Subtitle
- ASIC1 and ASIC3 Play Different Roles in the Development of Hyperalgesia After Inflammatory Muscle Injury
- Creators
- Roxanne Y Walder - Physical Therapy and Rehabilitation Science, Pain Research Program, University of Iowa, Iowa City, IowaLynn A Rasmussen - Physical Therapy and Rehabilitation Science, Pain Research Program, University of Iowa, Iowa City, IowaJon D Rainier - Department of Chemistry, University of Utah, Salt Lake City, UtahAlan R Light - Department of Anesthesiology, University of Utah, Salt Lake City, UtahJohn A Wemmie - Department of Psychiatry, University of Iowa, Iowa City, IowaKathleen A Sluka - Physical Therapy and Rehabilitation Science, Pain Research Program, University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- The journal of pain, Vol.11(3), pp.210-218
- DOI
- 10.1016/j.jpain.2009.07.004
- PMID
- 20015700
- NLM abbreviation
- J Pain
- ISSN
- 1526-5900
- eISSN
- 1528-8447
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2010
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute; Nursing; Physical Therapy and Rehabilitation Science; Neuroscience and Pharmacology; Neurosurgery
- Record Identifier
- 9984004182802771
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