Abstract
The aim of the study was to assess healing after capsaicin-induced SP depletion during rat Achilles tendon repair by biomechanical testing.
Capsaicin treatment reduced the concentrations of substance P (SP) by ~60% and calcitonin gene related peptide (CGRP) by ~40% as compared to the control group, as assessed by radioimmunoassay in the dorsal root ganglia (DRG), at 1 and 4 weeks post tendon rupture. Also the peripheral neuronal presence of SP and CGRP, 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 DRG (r=0.54, p=0.018). The reduced presence of SP/CGRP 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 due to 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 DRG 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 4 weeks.
In conclusion, rats with higher residual SP levels after capsaicin-induced neuropathy develop improved tensile strength and stress at failure in the healing Achilles tendon.