When chronic pain and age combine: Psychobiological bases of chronic pain during aging

eng Approximately 50% of individuals over the age of 65 experience chronic pain, which significantly impacts their physical and cognitive functioning, and overall quality of life. Given current demographic trends, this high prevalence and its associated challenges underscore the urgent need to better understand how aging influences the development and persistence of chronic pain. Building on evidence that chronic pain and aging induce similar neuroplastic changes, this thesis seeks to explore the psychobiological mechanisms underlying chronic pain in the aging population. The sample for studies 1- 4 consisted of three groups: older adults (>60 years) with chronic musculoskeletal pain, older adults (>60 years) without pain, and a group of young individuals without pain (50 years) with knee osteoarthritis. In Study 1, differences in temporal dynamics of brain activity were examined using electroencephalography (EEG) during painful and non-painful electrical stimulation in older adults with chronic pain. Main results revealed heightened frontoparietal cortical responses during painful stimulation, particularly in late-evoked potentials, suggesting an enhanced alarm/orienting response in this population. In Study 2, EEG was used to investigate attentional differences to somatosensory stimuli through an oddball paradigm with affective modulation. Results showed that older adults with chronic pain exhibited a somatosensory habituation impairment (enhanced N100) during frequent stimuli, which was more pronounced in affective contexts. In Study 3, functional magnetic resonance imaging (fMRI) revealed that altered resting-state functional connectivity (rsFC) within the pain network in older adults with chronic pain, particularly increased amygdala-dorsolateral prefrontal cortex connectivity, was linked to impaired pain inhibition. This suggests chronic pain may heighten amygdala projections to the frontal cortex, disrupting cognitive processes involved in pain control. Building on these findings, Study 4 examined how alterations in rsFC within the brain's major functional networks were associated with cognitive decline in older adults with chronic pain. Results indicated that increased connectivity within the Default Mode Network (DMN) was linked to poorer cognitive flexibility in older adults with chronic pain, impairing age-related compensatory mechanism. Finally, Study 5 examined how the chronic pain impact, defined as the degree of functional 1 limitation caused by pain, in middle-aged and older adults is associated with rsFC alterations within the Salience Network (SN) and its relationship with interoceptive sensitivity. Findings showed reduced SN connectivity in those with high-impact chronic pain. Chronic pain severity also modulated the link between SN connectivity and interoceptive attentional regulation, indicating that greater pain impact disrupts interoceptive mechanisms in older adults. Altogether, the findings of this thesis shed light on the various alterations caused by chronic pain in the perception of bodily sensations, pain inhibition, and cognitive decline. It proposes different psychobiological bases to explain these changes, aiming to understand the higher prevalence of pain in this population and adapt various intervention protocols to alleviate pain in this age group.