The non-noxious spinal input via large-diameter afferents can transsynaptically activate inhibitory interneurons, thereby ‘closing the gate’ for noxious stimuli (e.g., CRD and DARS) and preventing the uncontrolled reflex response (i.e., autonomic dysreflexia; Fig. 8). The gene discussed is DARS1; the disease is autonomic dysreflexia.