Pain in the Elderly: Role of Hyperalgesic Priming

The project proposes two main aims: (1) to establish if aged F344xBN rats express nociceptor plasticity (priming), determine the age at which it develops, and assess its association with systemic inflammation by measuring circulating inflammatory cytokines. (2) to identify mechanisms underlying priming in the elderly, specifically determining the role of Type I and Type II priming and the involved nociceptor populations. This aim also tests the hypothesis that systemic inflammation and increased reactive oxygen species (ROS) production by mitochondrial dysfunction lead to priming, evaluating ROS activity in dorsal root ganglia (DRG) via immunofluorescence, modulating mitochondrial electron chain transport, scavenging mitochondria-specific superoxide in vivo, and assessing oxygen consumption rate ex vivo using a seahorse analyzer in DRG neurons. All experiments will be conducted in both sexes to account for sex differences in pain syndromes and priming.