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.