Locomotor dysfunction and pain: the scylla and charybdis of fiber sprouting after spinal cord injury.
Injury to the spinal cord (SCI) can produce a constellation of problems including chronic pain, autonomic dysreflexia, and motor dysfunction. Neuroplasticity in the form of fiber sprouting or the lack thereof is an important phenomenon that can contribute to the deleterious effects of SCI. Aberrant sprouting of primary afferent fibers and synaptogenesis within incorrect dorsal horn laminae leads to the development and maintenance of chronic pain as well as autonomic dysreflexia. At the same time, interruption of connections between supraspinal motor control centers and spinal cord output cells, due to lack of successful regenerative sprouting of injured descending fiber tracts, contributes to motor deficits. Similarities in the molecular control of axonal growth of motor and sensory fibers have made the development of cogent therapies difficult. In this study, we discuss recent findings related to the degradation of inhibitory barriers and promotion of sprouting of motor fibers as a strategy for the restoration of motor function and note that this may induce primary afferent fiber sprouting that can contribute to chronic pain. We highlight the importance of careful attentiveness to off-target molecular- and circuit-level modulation of nociceptive processing while moving forward with the development of therapies that will restore motor function after SCI.
Deumens
Ronald
R
Pain Management and Research Center, Department of Anesthesiology, Maastricht University Hospital, P. Debyelaan 25, P.O. Box 5800, 6200 AZ, Maastricht, The Netherlands.
Joosten
Elbert A J
EA
Waxman
Stephen G
SG
Hains
Bryan C
BC
D000344:Afferent Pathways / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D002908:Chronic Disease; D020233:Gait Disorders, Neurologic / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D009416:Nerve Regeneration; D009473:Neuronal Plasticity; D009619:Nociceptors / Q000473:pathology / Q000503:physiopathology; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000150:complications / Q000503:physiopathology*; D013126:Spinal Nerve Roots / Q000473:pathology / Q000503:physiopathology