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Aging-associated decrease of PGC-1α promotes pain chronification
Xinbo Wu1, Liuyue Yang1, Zihua Li1
1Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Aging Cell
|May 18, 2024
Summary
Aging decreases PGC-1α in the brain, worsening chronic pain in older mice. Restoring PGC-1α in the primary somatosensory cortex (S1) alleviates this pain, offering a potential therapeutic target for chronic pain in aging populations.
Area of Science:
- Neuroscience
- Aging Research
- Pain Management
Background:
- Aging typically reduces somatosensory function, yet chronic pain is prevalent in older adults.
- The role of the primary somatosensory cortex (S1) in age-related pain processing and chronification remains unclear.
- Degenerative conditions like osteoarthritis contribute to pain in aging populations.
Purpose of the Study:
- To investigate how aging affects pain processing in the primary somatosensory cortex (S1).
- To determine if aging alters neural dynamics in S1 and promotes pain chronification.
- To explore the role of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) in age-related pain.
Main Methods:
- Utilized aged and mature adult mice models with nerve injury.
- Measured nociceptive behavior and analyzed PGC-1α expression in S1.
- Employed intravital two-photon calcium imaging to assess S1 neural dynamics.
- Used chemogenetics and viral vectors to manipulate S1 interneuron activity and PGC-1α levels.
Main Results:
- Older mice exhibited prolonged nociceptive behavior post-nerve injury compared to younger mice.
- Decreased PGC-1α expression in S1 of older mice correlated with prolonged pain.
- Both aging and PGC-1α deficiency led to altered S1 neural dynamics.
- Modulating S1 interneuron activity and PGC-1α levels impacted nociceptive behavior and neural dynamics.
Conclusions:
- Aging-associated reduction in PGC-1α in S1 contributes to pain chronification.
- Altering S1 neural dynamics, particularly PGC-1α levels in interneurons, can ameliorate age-related chronic pain.
- Targeting PGC-1α in S1 offers a potential strategy for managing chronic pain in older individuals.
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