Background & Aims
Tendon injury produces intractable pain and disability in movement. However, the medications for analgesia and restoring functional integrity of tendon are limited. In the present study, we aimed to investigate the role of the peripheral PAR2 activation in the pain development and tendon histopathological changes produced by Achilles tendon partial transection injury (TTI) in the adult, male Sprague-Dawley rats.
Methods
Experiments were performed in adult, male Sprague-Dawley rats. The Achilles tendon injury was mimicked by Achilles tendon partial transection injury (TTI). Mechanical allodynia, thermal hyperalgesia, spontaneous pain, and movement-evoked pain-like response were tested and used for evaluating pain produced by TTI. The combination of real-time quantitative PCR, Western blot analysis, in situ hybridization, immunofluorescence, histological evaluation, retrograde tracing of the sensory neuron innervation, and small-interference RNA (siRNA) knockdown of PAR2 were used.
Results
TTI treatment increased PAR2 protein expression in both somata of DRG neurons and their peripheral terminals within the injured Achilles tendon. Activation of PAR2 promoted the primary sensory neuron plasticity through activation of the downstream cAMP-PKA pathway, phosphorylation of PKC, CaMKII, and CREB. Blocking PAR2 signaling with PAR2 siRNA or the antagonistic peptide PIP delayed the onset of TTI-induced pain, reversed the ongoing pain, inhibited sensory nerve sprouting, and promoted structural remodeling of the injured tendon. Vitamin B complex (VBC) containing thiamine (B1), pyridoxine (B6), and cyanocobalamin (B12) was effective in ameliorating TTI-induced pain, inhibiting ectopic nerve sprouting, and accelerating tendon repair by suppressing PAR2 activation.
Conclusions
PAR2 signaling is crucial in the development of pain and histopathologic changes in injured tendons after an Achilles tendon injury. Targeting PAR2 signaling with drugs may be an effective approach to treating pain caused by tendon injury and promoting tendon repair. B vitamins could be a suitable option for reducing pain and promoting the repair of injured tendons.
References
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Presenting Author
Lihui Li
Poster Authors
Topics
- Specific Pain Conditions/Pain in Specific Populations: Neuropathic Pain - Peripheral