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

Scand J Med Sci Sports. 2011 Aug;21(4):562-9. doi: 10.1111/j.1600-0838.2009.01080.x. Epub 2010 Mar 10.


Tendon healing is characterized mostly by slow rehabilitation and, as in tendinopathy, aberrant, protracted sensory nerve ingrowth. This study investigated whether administration of the sensory neuropeptide substance P (SP) could enhance healing and modulate sensory nerve plasticity after Achilles tendon rupture. Fifty-four male Sprague-Dawley rats were allocated to three groups, all receiving six daily injections post-rupture of; (1) SP (10(-6) mol/kg body weight)+endopeptidase inhibitors captopril and thiorphan, (2) captopril/thiorphan only and (3) saline control. At 1, 3 and 6 weeks post-rupture tendon healing was evaluated by assessments of fibroblast proliferation, collagen III-LI (like) occurrence, diameter of newly organized collagen and sensory nerve fiber ingrowth. At 1 week, the SP-treated group exhibited increased occurrence of collagen III-LI (P=0.03) and of organized collagen (P=0.04) compared with control. At 3 weeks, the SP group notably displayed reduced SP-nerve fiber ingrowth (P=0.02), and higher fibroblast density (P=0.004). Both the SP and captopril/thiorphan groups demonstrated increase in collagen fiber organization compared with control (P=0.02 and 0.004, respectively). At 6 weeks, no significant differences were observed between the groups. SP supply in tendon repair promotes early tissue proliferation and regulation of endogenous sensory nerve ingrowth, suggesting implications for novel treatment in tendinopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / drug effects*
  • Fibroblasts / drug effects*
  • Male
  • Nerve Fibers / drug effects*
  • Nerve Fibers / metabolism
  • Nerve Tissue / drug effects*
  • Nerve Tissue / growth & development*
  • Neurotransmitter Agents / administration & dosage
  • Neurotransmitter Agents / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Tendon Injuries / therapy*


  • Neurotransmitter Agents