Apport du phénotypage neurovasculaire dans la prévention primaire et secondaire du syndrome du canal carpien – NEUROVASC

The carpal tunnel syndrome (CTS), the main musculoskeletal disorder, is due to chronic compression of the median nerve within a tunnel, leading to nervous and vasomotor dysfunctions of the hand. CTS is the first recognized professional complication and the first cause of surgery. The biomechanical and psychosocial factors involved in musculoskeletal disorders are well described, however the physiological underlying mechanisms are largely unknown. Although the surgery is the best way to relieve the pressure on the nerve in these patients, the nervous atrophy is often irreversible. It is then urgent to better understand the pathophysiological pathways involved in CTS in order to develop an appropriate therapy. We have shown that the increase in skin blood flow in response to local pressure application allows us to study in vivo the cutaneous interaction between nerve and vessels in a non invasive manner. This pressure-induced vasodilation (PIV) exists in humans and rodents and gives the opportunity to perform clinical and experimental studies in order to determine the underlying neural and microvascular physiopathological mechanisms in chronic nerve compression. Therefore the microvascular complications associated to CTS may be evaluated by the study of PIV. To go further in the understanding of the cutaneous microcirculation, iontophoresis induces the local transcutaneous diffusion of pharmacological molecules, preventing systemic response. The endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) microvascular responses can be performed in humans and animals. The main purpose of this project is to verify the effects of CTS in the development of PIV to better understand the underlying mechanisms: -Primary prevention: In order to characterize CTS patients, PIV will be assessed in a cutaneous area not affected by the CTS-induced microcirculatory complications. The study of PIV could help in the diagnosis of CTS. -Secondary prevention: If PIV is altered in subjects with CTS, we will evaluate the beneficial effects on the interaction between nerves and vessels in response to nerve decompression in studying PIV and endothelium-dependent and independent responses (at the diagnosis of CTS and 3 months following the surgery). - In order to go further in the understanding of the physiological and molecular mechanisms, experimental studies will be performed in rodents to assess the impairment of the neuro-microcirculation of both the compressed nerve and the cutaneous area innervated by the corresponding nerve. Expected results: In CTS patients, we expect a decrease of PIV that could be restored by nerve decompression. Animal experiments will help to establish a physiopathological model of CTS and we propose that PIV could be used to diagnose and predict CTS development. In conclusion, PIV, a novel physiological mechanism, allows testing the interaction between nerves and vessels and provides a unique experimental model to phenotype CTS physiopathology and open the way to neurovascular genotype in order to prevent CTS.