Adjuvant neuropeptides can improve neuropathic ligament healing in a rat model

Diminished healing in neuropathic tissues suggests an important regulatory role for peripheral neurogenic factors in connective tissue healing. Although neurogenic factors, including neuropeptides, can induce cell proliferation and influence inflammatory cell chemotaxis in vitro, there is little appreciation of the potential of neuropeptides to affect connective tissue healing in vivo. We created both efferent and afferent peripheral neuropathies in 55 female Wistar rats. First, we showed that neuropathy led to impaired healing of ruptured ligaments. We then showed that local delivery of specific neuropeptides could reverse the functional deficits of these neuropathic ligaments in only 2 weeks. In substance P and vasoactive intestinal peptide-treated medial collateral ligaments (MCLs), the mechanical properties of these healing neuropathic tissues returned to values at or above normally innervated, intact ligaments. In addition, neuropeptide Y stimulated MCL healing in this model. These findings suggest a new paradigm to improve neuropathic soft connective tissue healing.