Residual substance P levels after capsaicin treatment correlate with tendon repair

Abstract

The aim of the study was to assess healing after capsaicin-induced substance P (SP) depletion during rat Achilles tendon repair by biomechanical testing. Capsaicin treatment reduced the concentrations of SP by ∼60% and calcitonin gene-related peptide by ∼40% as compared with the control group, as assessed by radioimmunoassay in the dorsal root ganglia, at 1 and 4 weeks post-tendon rupture. Also, the peripheral neuronal presence of SP and calcitonin gene-related peptide, as assessed by immunohistochemistry, was lower at both weeks 1 and 4. The decreased peripheral neuronal presence of SP at week 1 correlated with the corresponding levels in the dorsal root ganglia (r = 0.54, p = 0.018). The reduced presence of SP/calcitonin gene-related peptide after capsaicin treatment was verified by a decreased sensitivity to painful mechanical and thermal stimuli (p < 0.05). Correlation analyses between individual residual SP levels and biomechanical tissue properties were performed because of differences in failure mode between the groups and high individual variations in the SP levels after capsaicin treatment. Thus, the residual SP levels in the dorsal root ganglia correlated with transverse area, ultimate tensile strength, and stress at failure (r = 0.39, p = 0.036; r = 0.53, p = 0.005; and r = 0.43, p = 0.023, respectively). Furthermore, individual pain sensitivity at week 2 correlated with peripheral occurrence of SP and was correlated with tensile strength and stress at failure (r = 0.89, p = 0.006 and r = 0.78, p = 0.015) at week 4. In conclusion, rats with higher residual SP levels after capsaicin-induced neuropathy develop improved tensile strength and stress at failure in the healing of Achilles tendon.

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

“…1). 6,10 Specific sensory denervation results in delayed reepithelialization, as well as hindered tendon wound healing. 6,10,11 Treatment with capsaicin also delays healing of gastric mucosal injuries.…”

“…1). 10 Thus, capsaicin-mediated denervation is believed to exert its effects mainly via SP-and secondly by CGRPinhibition. Higher residual SP levels in rats treated with capsaicin correlated with better resultant biomechanical tissue properties of the scar tissue, that is, transverse area, ultimate tensile strength and stress at failure.…”

“…Higher residual SP levels in rats treated with capsaicin correlated with better resultant biomechanical tissue properties of the scar tissue, that is, transverse area, ultimate tensile strength and stress at failure. 10 Effects of neuropeptides on healing processes. During the inflammatory phase of healing, increased levels of SP-and CGRP-positive nerve fibers locate in blood vessel walls surrounded by inflammatory blood derived cells (e.g., platelets and growth factors) in the associated loose connective tissue (Fig.…”

“…Exogenous administration of SP promoted wound and tendon healing. 10,[36][37][38][39] Moreover, inhibition of neutral endopeptidase, which degrades SP, augments epithelialization. 40 Thus, an exogenous SP supply after tendon injury resulted in increased fibroblast number, diameter of the organized collagen, and the amount of collagen III after injury (Fig.…”

The Implication of Substance P in the Development of Tendinopathy: A Case Control Study

“…It has also been shown that tenocytes have the ability to produce neuro-mediators on their own in tendinopathy [15]. In acute tendon injury or rupture, SP is known to be involved in tissue healing through multiple functions such as inflammatory response, pain transmission, increased vascular permeability and blood flow, and cellular proliferation [6,16,17,18]. However, the actual role of SP among the various neuro-mediators in the pathogenesis of degenerative tendinopathy (e.g., chronic tendon injury) is still being debated.…”