NDLI: ASIC3 Is Required for Development of Fatigue-Induced Hyperalgesia

Content Provider	Springer Nature Link
Author	Gregory, Nicholas S. Brito, Renan G. Fusaro, Maria Cláudia G. Oliveira Sluka, Kathleen A.
Copyright Year	2015
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.
Starting Page	1020
Ending Page	1030
Page Count	11
File Format	PDF
ISSN	08937648
Journal	Molecular Neurobiology
Volume Number	53
Issue Number	2
e-ISSN	15591182
Language	English
Publisher	Springer US
Publisher Date	2015-01-11
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pain Exercise Proton Acid ASIC Hyperalgesia Macrophage Neurosciences Neurobiology Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neurology Cellular and Molecular Neuroscience

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Liver X Receptor β Is Involved in Formalin-Induced Spontaneous Pain

Glucocorticoid-Potentiated Spinal Microglia Activation Contributes to Preoperative Anxiety-Induced Postoperative Hyperalgesia

HDAC3 Is Required for Posterior Lateral Line Development in Zebrafish

IL-10 Cytokine Released from M2 Macrophages Is Crucial for Analgesic and Anti-inflammatory Effects of Acupuncture in a Model of Inflammatory Muscle Pain

Can Exercise Ameliorate Aromatase Inhibitor-Induced Cognitive Decline in Breast Cancer Patients?

SDF1-CXCR4 Signaling Contributes to the Transition from Acute to Chronic Pain State

Lamin A/C Is Required for ChAT-Dependent Neuroblastoma Differentiation

LSD1 is Required for Hair Cell Regeneration in Zebrafish

Maternal Hypothyroxinemia-Induced Neurodevelopmental Impairments in the Progeny

ASIC3 Is Required for Development of Fatigue-Induced Hyperalgesia

Similar Documents

Liver X Receptor β Is Involved in Formalin-Induced Spontaneous Pain

Glucocorticoid-Potentiated Spinal Microglia Activation Contributes to Preoperative Anxiety-Induced Postoperative Hyperalgesia

HDAC3 Is Required for Posterior Lateral Line Development in Zebrafish

IL-10 Cytokine Released from M2 Macrophages Is Crucial for Analgesic and Anti-inflammatory Effects of Acupuncture in a Model of Inflammatory Muscle Pain

Can Exercise Ameliorate Aromatase Inhibitor-Induced Cognitive Decline in Breast Cancer Patients?

SDF1-CXCR4 Signaling Contributes to the Transition from Acute to Chronic Pain State

Lamin A/C Is Required for ChAT-Dependent Neuroblastoma Differentiation

LSD1 is Required for Hair Cell Regeneration in Zebrafish

Maternal Hypothyroxinemia-Induced Neurodevelopmental Impairments in the Progeny

ASIC3 Is Required for Development of Fatigue-Induced Hyperalgesia