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Roles of ASIC3, TRPV1, and NaV1.8 in the transition from acute to chronic pain in a mouse model of fibromyalgia.
- Source :
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Molecular pain [Mol Pain] 2014 Jun 23; Vol. 10, pp. 40. Date of Electronic Publication: 2014 Jun 23. - Publication Year :
- 2014
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Abstract
- Background: Tissue acidosis is effective in causing chronic muscle pain. However, how muscle nociceptors contribute to the transition from acute to chronic pain is largely unknown.<br />Results: Here we showed that a single intramuscular acid injection induced a priming effect on muscle nociceptors of mice. The primed muscle nociceptors were plastic and permitted the development of long-lasting chronic hyperalgesia induced by a second acid insult. The plastic changes of muscle nociceptors were modality-specific and required the activation of acid-sensing ion channel 3 (ASIC3) or transient receptor potential cation channel V1 (TRPV1). Activation of ASIC3 was associated with increased activity of tetrodotoxin (TTX)-sensitive voltage-gated sodium channels but not protein kinase Cϵ (PKCϵ) in isolectin B4 (IB4)-negative muscle nociceptors. In contrast, increased activity of TTX-resistant voltage-gated sodium channels with ASIC3 or TRPV1 activation in NaV1.8-positive muscle nociceptors was required for the development of chronic hyperalgesia. Accordingly, compared to wild type mice, NaV1.8-null mice showed briefer acid-induced hyperalgesia (5 days vs. >27 days).<br />Conclusion: ASIC3 activation may manifest a new type of nociceptor priming in IB4-negative muscle nociceptors. The activation of ASIC3 and TRPV1 as well as enhanced NaV1.8 activity are essential for the development of long-lasting hyperalgesia in acid-induced, chronic, widespread muscle pain.
- Subjects :
- Acid Sensing Ion Channels genetics
Acute Pain metabolism
Aniline Compounds therapeutic use
Animals
Cells, Cultured
Chronic Pain metabolism
Disease Models, Animal
Dose-Response Relationship, Drug
Enzyme Inhibitors therapeutic use
Fibromyalgia chemically induced
Furans therapeutic use
Ganglia, Spinal cytology
Hyperalgesia drug therapy
Hyperalgesia etiology
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Muscle, Skeletal drug effects
NAV1.8 Voltage-Gated Sodium Channel genetics
Sodium Channel Blockers therapeutic use
TRPV Cation Channels antagonists & inhibitors
TRPV Cation Channels genetics
Acid Sensing Ion Channels metabolism
Acute Pain etiology
Chronic Pain etiology
Fibromyalgia complications
NAV1.8 Voltage-Gated Sodium Channel metabolism
TRPV Cation Channels metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1744-8069
- Volume :
- 10
- Database :
- MEDLINE
- Journal :
- Molecular pain
- Publication Type :
- Academic Journal
- Accession number :
- 24957987
- Full Text :
- https://doi.org/10.1186/1744-8069-10-40