Afferent and Sympathetic Innervation in Muscle Growth and Contractures

We have demonstrated in our mouse model of neonatal brachial plexus injury (NBPI) that impaired growth of denervated muscle contributes to contracture formation. However, the relative contribution of motor (efferent) versus sensory (afferent) and sympathetic denervation to contracture pathophysiology is unknown. Clinical evidence suggests that preservation of afferent and/or sympathetic innervation protects against contractures, as children with neonatal pre-ganglionic nerve root injuries do not develop contractures, whereas post-ganglionic injuries routinely cause contractures.

Using our mouse model, we have shown that preservation of afferent innervation by pre-ganglionic NBPI, which preserves sympathetic and afferent innervation to the muscle (Figure 4), prevents contractures even with severe efferent denervation. We aim to identify the relative roles of afferent and sympathetic innervation to this protective effect on muscle growth, as well as the molecular mechanisms by which this protective effect is mediated. Ultimately, we aim to medically recapitulate this protective effect in children with NBPI and Cerebral Palsy.

This research has been funded by the American Foundation for Surgery of the Hand and the National Institutes of Health – Eunice Kennedy Shriver National Institute of Child Health and Human Development.