| Title |
ASIC3 Is Required for Development of Fatigue-Induced Hyperalgesia
|
|---|---|
| Published in |
Molecular Neurobiology, January 2015
|
| DOI | 10.1007/s12035-014-9055-4 |
| Pubmed ID | |
| Authors |
Nicholas S. Gregory, Renan G. Brito, Maria Cláudia G. Oliveira Fusaro, Kathleen A. Sluka |
| Abstract |
An acute bout of exercise can exacerbate pain, hindering participation in regular exercise and daily activities. The mechanisms underlying pain in response to acute exercise are poorly understood. We hypothesized that proton accumulation during muscle fatigue activates acid-sensing ion channel 3 (ASIC3) on muscle nociceptors to produce hyperalgesia. We investigated the role of ASIC3 using genetic and pharmacological approaches in a model of fatigue-enhanced hyperalgesia. This model uses two injections of pH 5.0 saline into muscle in combination with an electrically induced fatigue of the same muscle just prior to the second injection of acid to induce mechanical hyperalgesia. We show a significant decrease in muscle force and decrease in muscle pH after 6 min of electrical stimulation. Genetic deletion of ASIC3 using knockout mice and pharmacological blockade of ASIC3 with APETx2 in muscle prevents the fatigue-enhanced hyperalgesia. However, ASIC3(-/-) mice and APETx2 have no effect on the fatigue response. Genetic deletion of ASIC3 in primary afferents innervating muscle using an HSV-1 expressing microRNA (miRNA) to ASIC3 surprisingly had no effect on the development of the hyperalgesia. Muscle fatigue increased the number of macrophages in muscle, and removal of macrophages from muscle with clodronate liposomes prevented the development of fatigue-enhanced hyperalgesia. Thus, these data suggest that fatigue reduces pH in muscle that subsequently activates ASIC3 on macrophages to enhance hyperalgesia to muscle insult. |
X Demographics
The data shown below were collected from the profiles of 12 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | 8% |
| India | 1 | 8% |
| United Kingdom | 1 | 8% |
| United States | 1 | 8% |
| Ireland | 1 | 8% |
| Unknown | 7 | 58% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 12 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 66 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 66 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 12 | 18% |
| Student > Ph. D. Student | 8 | 12% |
| Student > Master | 8 | 12% |
| Student > Doctoral Student | 6 | 9% |
| Professor > Associate Professor | 5 | 8% |
| Other | 15 | 23% |
| Unknown | 12 | 18% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 11 | 17% |
| Medicine and Dentistry | 10 | 15% |
| Biochemistry, Genetics and Molecular Biology | 8 | 12% |
| Agricultural and Biological Sciences | 6 | 9% |
| Nursing and Health Professions | 3 | 5% |
| Other | 11 | 17% |
| Unknown | 17 | 26% |
Attention Score in Context
This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 December 2023.
All research outputs
#5,340,716
of 25,584,565 outputs
Outputs from Molecular Neurobiology
#1,293
of 3,991 outputs
Outputs of similar age
#68,563
of 359,748 outputs
Outputs of similar age from Molecular Neurobiology
#13
of 61 outputs
Altmetric has tracked 25,584,565 research outputs across all sources so far. Compared to these this one has done well and is in the 79th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,991 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.4. This one has gotten more attention than average, scoring higher than 67% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 359,748 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 80% of its contemporaries.
We're also able to compare this research output to 61 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.