Topical glyceryl trinitrate and noninsertional Achilles tendinopathy: a clinical and cellular investigation

Am J Sports Med. 2008 Jun;36(6):1160-3. doi: 10.1177/0363546508314423. Epub 2008 Mar 21.


Background: Topical glyceryl trinitrate (GTN) therapy has been advocated in the treatment of Achilles tendinopathy. The mechanism of action is unknown but may be related to modulation of local nitric oxide levels.

Hypothesis: Topical GTN therapy for noninsertional Achilles tendinopathy will significantly enhance clinical improvement and will be associated with increased collagen synthesis within the tendon.

Study design: Randomized controlled clinical trial; Level of evidence, 1.

Methods: Forty patients were recruited. Twenty underwent standard nonoperative physical therapy, and 20 underwent physical therapy and topical GTN daily. Clinical outcome was assessed using the Ankle Osteoarthritis Scale (AOS) visual analog score. Patients who failed to improve with conservative measures and who underwent surgical decompression had histological and immunohistochemical examination of samples from the Achilles tendon.

Results: Glyceryl trinitrate did not offer any additional clinical benefit over standard nonoperative treatment for noninsertional Achilles tendinopathy. After 6 months of treatment, there was no significant difference in scores between the groups for pain (3.0 vs 3.1, P = .42) or disability (2.15 vs 2.25, P = .38). Histological examination did not show any difference in neovascularization, collagen synthesis, or stimulated fibroblasts between the 2 groups. There was no evidence of modulation of nitric oxide synthase, a marker of nitric oxide production, in those tendons treated with GTN.

Conclusion and clinical relevance: This study has failed to support the clinical benefit of GTN patches previously described in the literature. In the available tissue samples, there did not appear to be any histological or immunohistochemical change in Achilles tendinopathy treated with GTN compared with those undergoing standard nonoperative therapy.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Achilles Tendon* / pathology
  • Administration, Topical
  • Adult
  • Aged
  • Combined Modality Therapy
  • Humans
  • Middle Aged
  • Nitroglycerin / administration & dosage*
  • Physical Therapy Modalities
  • Statistics, Nonparametric
  • Tendinopathy / drug therapy*
  • Tendinopathy / pathology
  • Tendinopathy / rehabilitation


  • Nitroglycerin