A Breakthrough in Treating Autonomic Dysreflexia After Spinal Cord Injury
Autonomic dysreflexia is a serious and potentially life-threatening condition that affects people with spinal cord injuries (SCI). It causes sudden episodes of uncontrolled high blood pressure triggered by sensory stimuli, such as bladder or bowel distension. Until now, the underlying neuronal mechanisms were poorly understood, limiting treatment options.
Mapping the Hidden Neural Circuit
Researchers from the University of Calgary, EPFL, and CHUV have identified the neuronal architecture responsible for autonomic dysreflexia. Using mouse models, single-nucleus RNA sequencing, and advanced neural tracing techniques, they uncovered a pathological chain of neurons that reorganizes after SCI:
- Nociceptive sensory neurons (Calca⁺) in the dorsal root ganglia send abnormal signals.
- These signals activate excitatory Vsx2⁺ neurons in the lumbosacral spinal cord.
- These neurons project to the lower thoracic spinal cord, activating local Vsx2⁺ neurons.
- These, in turn, stimulate ChAT⁺ sympathetic neurons, causing dangerous spikes in blood pressure.
A Promising Electrical Therapy
The researchers also showed that targeted epidural electrical stimulation (EES) over the lower thoracic spinal cord can activate a competing, beneficial neural circuit. This stimulation recruits large-diameter proprioceptive fibers (PV⁺), which activate the same Vsx2⁺ neurons but in a way that safely regulates blood pressure.
Toward Personalized Neurotherapy
By applying EES daily (a protocol called autonomic neurorehabilitation), the team successfully reversed autonomic dysreflexia in mice, rats, and humans with SCI. Preliminary clinical trials showed a significant reduction in symptoms like headaches and heart palpitations, with no serious side effects.
The Importance of Precision
The study warns against misdirected stimulation (e.g., over the lumbosacral spinal cord), which can worsen autonomic dysreflexia by reinforcing the pathological neural architecture.
Conclusion: This research paves the way for pivotal clinical trials to validate the safety and effectiveness of targeted EES as a mechanistic and personalized therapy for autonomic dysreflexia in people living with spinal cord injuries.
References
Soriano, J.E., Hudelle, R., Mahe, L. et al. A neuronal architecture underlying autonomic dysreflexia. Nature (2025). https://doi.org/10.1038/s41586-025-09487-w
Phillips, A.A., Gandhi, A.P., Hankov, N. et al. An implantable system to restore hemodynamic stability after spinal cord injury. Nat Med 31, 2946–2957 (2025). https://doi.org/10.1038/s41591-025-03614-w