Adjuvant neuropeptides can improve neuropathic ligament healing in a rat model

Abstract

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. ß

Substance P injections enhance tissue proliferation and regulate sensory nerve ingrowth in rat tendon repair

“…Today there are no available treatments which dramatically can promote tendon healing, especially in tendinopathic patients. The present study corroborates the conception that exogenous sensory neuropeptide SP supply can enhance tendon/ligament healing (Burssens et al, 2005; Steyaert et al, 2006; Grorud et al, 2007). Biomechanical studies suggest that SP may today be one of the most potent mediators to affect soft tissue healing (Grorud et al, 2007).…”

Influence of Comorbidities: Neuropathy, Vasculopathy, and Diabetes on Healing Response Quality

“…To see this illustration in color, the reader is referred to the web version of this article at www .liebertpub.com/wound of intact, uninjured MCLs. 41 The supply of SP, VIP, and NPY also significantly improved the histological appearance of the healing MCLs. Treated ligaments showed more organized scars and the appearance of increased matrix production.…”

“…37 One study assessed the effect of exogenous neuropeptide administration on the healing of denervated ligaments in rats. 41 The aim was to restore the neuronal supply to improve the healing responses of the medial collateral ligament (MCL) in joints partially denervated by femoral nerve transection or surgical sympathectomy. In this study, exogenous SP, VIP, and NPY all led to improved healing of denervated MCLs.…”

Nociceptive sensory innervation of the posterior cruciate ligament in osteoarthritic knees

“…Therefore, our results showed that, comparing with the normal knees, there was a signiWcant decrease in total innervation of the PCL including a subpopulation of proprioceptive and sympathetic nerves in the OA knees. Because peripheral nerves within the ligament play an essential role in homeostasis of ligaments and joints [19,20], the decrease in total innervations can be detrimental to the structural integrity of ligaments and joints.…”