Comparative Pain Expression and Its Association to Intestinal Microbiota Through the MI-RAT© Osteoarthritis Model Induced in LOU/C/Jall and Sprague-Dawley Aged Rats

To investigate the involvement of gut-brain axis in musculoskeletal chronic pain in the elderly, this preclinical study aimed to compare osteoarthritis (OA) pain expression, cognitive function and gut microbiota composition in two aging rat strains (11-15 months). A validated surgically induced OA model was used in Sprague-Dawley (SD; <i>n</i> = 12), as standard group, and in LOU/C/Jall rats (LOU; <i>n</i> = 8), a healthy aging model. The OA pain response was assessed longitudinally (60 days) through quantitative sensory testing (mechanical sensitization and endogenous inhibitory control functionality), spatial memory, and gut microbiota. At sacrifice, joint structural alterations and spinal neuropeptides concentrations were quantified. After OA induction, higher mechanical hypersensitivity in LOU than in SD was also associated with higher endogenous inhibitory control (<i>p</i> < 0.05). Expression of pro-/anti-nociceptive spinal neuropeptides, cognitive function and joint alterations were similar in both groups. Gut microbiota composition was different (<i>p</i> < 0.001) and different taxa were associated with each strain (e.g., <i>Akkermansia</i> spp. with LOU vs. <i>Lactobacillus</i> spp. with SD). This study suggests healthy aging to be associated with more efficient endogenous pain control and expression of specific intestinal bacteria. This research questions the implication of the intestinal microbiota in aging and chronic pain control.