L’effet du vieillissement normal sur les mécanismes centraux de la régulation de la douleur

Elderly have to deal daily with chronic pain. The diffuse inhibitory descending controls (DNIC) are much involved in the pain control. It was shown that the DNIC recruitment was lower in elderly than in young population, using the analgesic effect of the heterotopic noxious counter stimulation (HNCS), a protocol allowing testing the efficiency of the DNIC. However, the studies assessing the central sensitization by the temporal summation of pain after repetitive stimuli have reported mixed results, the effect of age is still unclear. In addition, there is an age-related decline of an important component, which has an influence on pain perception, the cognitive resources and especially the cognitive inhibition. The goal of this work is to understand the underling mechanisms of the chronic pain related to the normal aging, which can leads to a new therapeutic perspectives.   First, the recruitment of the CIDN was compared between healthy young and elderly participants using the HNCS, and the central sensitization was tested using TS. The sural nerve electric shock stimulation was chosen, because it allows us to have two measures, the pain rating and the nociceptive spinal reflex (RIII), an indicative measure of the nociception. Our participants were also invited to participate in a cognitive task (the Stroop), to assess the cognitive inhibition. Second, the efficacy of the CIDN and the cognitive inhibition in elderly and young participants was tested, but this time in a magnetic resonance imaging session. We have wanted to test the association between these two-psychophysics measures, with the cortical thickness of the regions involved into these two processes, and the effect of the normal aging on them. The results have showed a less recruitment of the DNIC in elderly in the HNCS experiment. Also, the elderly have performed less than young in the cognitive inhibition. In addition, a correlation between the cognitive inhibition and the modulation of the RIII-reflex was found. For the TS experiment, no difference was shown between the two groups, suggesting that aging may affect differently the mechanisms involved in endogenous pain modulation. The morphometric study has showed a global diminution of the cortical thickness with aging. Furthermore, there was an association, between the HNCS analgesia and the performance in cognitive inhibition, and between theses two processes and the cortical thickness of the left lateral OFC. These results suggest an eventual existence of at least a partial neuronal common network for the sensorial and cognitive descending inhibitory control.  This thesis has showed that the effect of normal aging on the central mechanisms of the pain regulation might be not uniform. Also, on one hand a correlation between the endogenous modulation of pain and cognitive inhibition was reported, and on the other hand that these two processes would be related to the same cortical area. Together, these findings would help to develop new therapeutic methods and offer more options to the management of pain in the elderly.

Keyphrases: Modulation, Cognition, OFC, Aging, Pain, Diffuse noxious inhibitory control