The association of pain with intrinsic capacity and the moderating role of inflammation in France: a cross-sectional analysis of the INSPIRE-T project

BACKGROUND: Although pain singularly impacts most critical domains of health status, its relationship with intrinsic capacity has been poorly investigated. Inflammation is central to pain biology, and longitudinal evidence indicates that pain can amplify inflammatory activity over time. This study evaluated the cross-sectional association of pain with intrinsic capacity and its domains in a cohort of community-dwelling people across the lifespan, as well as the moderating role of the inflammatory ageing (iAge) clock in this association. The secondary objective was to explore whether the pain-intrinsic capacity associations varied as a function of age and sex. METHODS: The analyses included 971 participants from the INSPIRE-T cohort. INSPIRE-T is an ongoing 10-year observational study in Toulouse, France, that recruited individuals aged 20 years and older who were not affected by severe illness that could compromise life expectancy within 5 years (or within 1 year for individuals who were already disabled and at old age). Pain was assessed based on self-reported presence over the previous 8 days, using a numeric scale (0-4, where higher is worse). A composite intrinsic capacity score (calculated as the arithmetic mean of the scores across the five domains) and intrinsic capacity domains (locomotion, cognition, vitality, psychology, and sensory capacity, including visual and hearing capacities) were assessed. Estimates from the regression models should be interpreted inversely (eg, a positive regression coefficient indicates a negative association), except for the vitality domain. Multiple linear regressions analyses were conducted to examine the association of pain with intrinsic capacity and its domains, as well as the interaction with iAge (pain × iAge), age (pain × age) and sex (pain × sex). The INSPIRE Platform is registered with ClinicalTrials.gov, NCT04224038. FINDINGS: Enrolment began on Oct 16, 2019, and the majority of participants were recruited by December, 2021. A total of 1014 individuals were recruited in the INSPIRE-T cohort; of those, 971 individuals (median age 64 years [IQR 48-77], range 20-102 years; 366 [38%] male and 605 female [62%] individuals) with complete pain data and intrinsic capacity evaluation data were included in the analysis. Both moderate pain (β 0·264, SE 0·076, p=0·0006) and intense pain (0·479, 0·105, p<0·0001) were negatively associated with intrinsic capacity values. Pain at all intensities, mild (0·512, 0·163, p=0·0017), moderate (1·111, 0·191, p<0·0001), or intense (1·532, 0·263, p<0·0001), was significantly associated with lower scores in the psychological domain. Intense pain was associated with reduced scores in all intrinsic capacity domains (locomotor: 0·857, 0·219, p<0·0001; vitality: -4·159, 1·742, p=0·017; cognitive: 0·499, 0·184, p=0·0069; and psychological: 1·532, 0·263, p<0·0001) except the sensory domain (-0·199, 0·349, p=0·57). Moderate pain was also associated with reduced scores in the locomotion domain (0·383, 0·160, p=0·017) and the vitality domain (-2·891, 1·269, p=0·023). INTERPRETATION: Pain was associated with reduced intrinsic capacity, with no evidence of a moderating role of iAge in this association. Higher pain intensities were linked to lower scores in all domains defining intrinsic capacity, except the sensory domain. At moderate intensities, the association was particularly evident in the vitality, locomotor, and psychological domains. Further research is needed to determine whether effective pain management could help prevent declines in intrinsic capacity. FUNDING: Agence Nationale de la Recherche.