Directed Functional Reinnervation to Curb Nociception and Enable Sensation

Peripheral nerve injuries lead to diminished function and pain via nociplastic phenomena. We propose a new strategy called Directed Functional Reinnervation, in which nerves are reassigned to new peripheral targets with the goal of altering circuit function. Here, we redirect pure sensory nerves into skeletal muscle grafts to curb nociplasticity and provide benign or useful inputs for prosthetic applications. Electrophysiological characterization of the functional signaling capabilities demonstrated robust afferent responses to mechanical stimuli. Immunofluorescence staining of the saphenous nerve graft indicated widespread innervation of various synapses within the muscle. With immediate graft placement, the injured nerves' dorsal root ganglia revealed comparable levels of nociceptive markers to uninjured nerves, suggesting a molecular basis for the prevention of pain sensitization. These findings support the use of skeletal muscle grafts for the alleviation of neuropathic pain and use as a sensory transmitter in conjunction with neural interfaces. Overall design: RNA seq profiling of dorsal root ganglia, comparing expression levels in unoperated controls with those upstream of saphenous nerve and skeletal muscle grafts