The role of neuropeptides in neuropathic and normal MCL healing

The peripheral nervous system mediates physiological responses to healing in a number of soft connective tissues. In particular, peripheral neuropeptides have been shown to have trophic effects, recruit inflammatory cells, and control local blood flow in injured soft tissues. In addition, neuropeptide concentrations increase in the plasma of patients with a number of injures, including ligament sprains. Ligament sprains are difficult to treat and result in long-term mechanical and biological deficits. Methods to augment ligament healing, including cytokine delivery, hemorrhaging, and stem cell therapy, have had limited success. Even though the peripheral nervous system is believed to play a role in soft tissue healing, its role in ligament healing (and other orthopedic tissue healing) has been largely ignored. The data contained herein demonstrated a significant role for the peripheral nervous system in ligament homeostasis and healing. Systemic and selective denervation of the autonomic and sensory branches of the peripheral nervous system results in functional deficits in healing MCL and altered MCL physiology. In addition, local delivery of specific neuropeptides (SP and VIP) leads to complete reversal of functional deficits induced by dennervation. These neuropeptides also improve healing of fully innervated MCLs, indicating a potential therapeutic role for neuropeptides in ligament healing. The work contained herein represents a new paradigm for the treatment of normal and neuropathic soft connective tissue injury.