As we age, our senses, particularly sight and hearing, gradually deteriorate. Similarly, our ability to perceive touch-related sensations like cold, heat, movement, and vibration also declines. However, the sensation of pain does not diminish in the same way. In fact, aging is commonly associated with an increase in chronic pain, which can often be linked to conditions such as arthritis. Additionally, research focused on the primary somatosensory cortex (S1), a crucial area of the brain involved in pain signal processing, indicates that pathways responsible for inhibiting pain are less effective as we age.
Previous studies have revealed that PGC-1a, a key player in mitochondrial development and operation, also impacts neuronal functions, particularly in neurons that process pain signals. Nonetheless, the interplay among PGC-1a, the S1 pain sensation, and aging has not been thoroughly investigated.
This study involved two groups of wild-type Black 6 mice, one group aged 4 weeks and the other 18 weeks. It was found that the younger mice exhibited almost three times as much PGC-1a expression compared to the older group. The mice underwent an injury involving constriction of the sciatic nerves to their hind legs. Recovery was slower in the older mice, who displayed increased sensitivity to touch and for an extended duration. The researchers describe this phenomenon as ‘aging-associated pain chronification.’
In a subsequent experiment, the researchers developed a group of mice with only one functional allele of PGC-1a, as opposed to normal mice that possess two. At 4 weeks old, both groups were subjected to the same type of injury as in the previous study. The mice with diminished PGC-1a expression suffered more severely than the older mice, with none fully recovering within 7 weeks. This effect was consistent across both male and female mice.
Following leg injuries, the brain activity of both younger and older mice was analyzed. On day 7, activity levels in the S1 excitation neurons were similar across both age groups. By day 35, however, the increased activity had subsided in the younger mice, whereas it remained significantly higher in the older mice. Activity in interneurons, which link the S1 to other parts of the brain, was reduced in both groups on day 7, but by day 35, it had only returned to normal in the younger mice. Subsequent testing with highly targeted drugs revealed that increased interneuron activity correlated with behaviors indicative of reduced chronic pain.
By employing an adeno-associated virus (AAV) to enhance PGC-1a production in older animals, researchers were able to reduce their chronic pain post-injury to levels comparable to those observed in younger animals. Additionally, similar to the younger animals, there was a decrease in excitation neuron activity and an increase in interneuron activity observed on day 35 after the injury.
These findings indicate that chronic pain in older adults is not solely due to conditions like arthritis but can also stem from a decline in vital brain functions related to aging. Consequently, future treatments that aim to restore these brain functions could play an essential role in alleviating such pain.
To view the original scientific study click below:
Aging-associated decrease of PGC-1a promotes pain chronification
