Chronic pain

Evolution of the definition

Descartes pain concept

pain is produced by a direct, straight-through transmission system from injured tissues in the body to a pain center in the brain

Evolution of the theory

Brain Imaging Biomarkers for Chronic Pain

Following the same injury, clinical outcomes can be opposite ranging from pain subsidization as the injury resolves within a normal healing period to the development of chronic pain that can persist for years or decades. Only a minority of patients remain in the latter, suggesting that they are predisposed to develop chronic pain. It was shown that brain function and moreover brain structure present some level of heritability (Thompson et al., 2001, 2013). In WM, evidence from molecular studies show the central role of gene-expression in the gradients that guide axons to their target during brain development (Dickson, 2002; Goodhill, 2016). However, genetic influences are not uniformly distributed throughout the brain, with phenotypic variation in certain regions and connections being under stronger genetic control than others.(Arnatkeviciute et al., 2021) Therefore, it would be interesting to compare the altered WM regions shown in this study with a heteribility atlas.

Chronic pain may be the result of a maladaptive maladaptive CNS plasticity. This theory notably supported by Herta Flor and Rohini Kuner In the timeframe of a couple months, brain plasticity and structural reorganization of synapses, cells and circuits can occur. It is thought that maladaptive reorganization could contribute to the chronification of pain. neurogenesis Pain can alter adult hippocampal neurogenesis. Notably, proliferation of the neuroblast in the subventricular zone and survival of the newborn neurons are negatively affected in neuropathic pain. Interestingly, stress both exacerbates pain chronicity in humans and inhibits hippocampal neurogenesis. Structure function change in glia Post-mortem analysis, showed that only patients with painful neuropathy showed increased astrocyte proliferation and activation. Recently, integrated PET-MRI studies show higher TPSO-uptake in the thalamus and the somatosensory cortex. Finally, genetically induced ablation of oligodendrocyte in mice evokes classical symptoms of neuropathic pain long before demyelation. This is important in light of the white-matter tract defects and maladaptive regenerative plasticity observed in chronic pain.

Tau protein could play an important role in the development of cognitive impairment associated with chronic pain. In fact it is thought that chronic pain leads to the accumulation of pathological forms of tau protein in the hippocampus, resulting in neuronal atrophy and cognitive impairment.

Neuroinflammation and microgliosis are also thought to affect the areas of the brain involved in emotional and cognitive components of pain. Free-water fraction (FW) and apparent fiber density (AFD) are two recently developed diffusion MRI (DMRI) white matter (WM) measures associated with neuroinflammation. Further investigation and correlation using PET scan could be of interest. Notably, several studies have underlined the potential of Diffusion MRI to investigate the glymphatic system