Topical nitroglycerin decreases pain intensity in daily activities: a review

To review the evidence for the effectiveness of topical nitroglycerin in treating acute and chronic tendinopathies among adults.

The investigators searched 27 databases for experimental studies, published from January 1990 to March 2009 in any language, on nitroglycerin application for tendon injuries. Further studies were sought from the reference lists of relevant articles.

Selection criteria were randomized controlled trials (RCTs) and other clinical controlled trials that compared topical nitroglycerin with placebo, an alternative intervention, or a standard treatment for acute (<2 weeks), subacute (2-6 weeks), or chronic (>6 weeks) tendinopathy; adult participants; and reduction of pain as an outcome measure. The search identified 163 published articles, of which 7 RCTs were included.

Details of the study design, participants, interventions, and outcomes (primarily pain, and secondarily range of motion and strength of the involved musculotendinous units) were extracted. Quality was evaluated by the Standard Quality Assessment Criteria for Evaluating Research Papers (14 points, scored 2 for "yes" and 1 for "partial"). Data assessment was done by 2 independent reviewers.

Glyceryl trinitrate was compared with placebo in 5 studies, 1 study compared nitroglycerin with local corticosteroid/anesthetic solution, and 1 study compared nitroglycerin and tendon rehabilitation with tendon rehabilitation alone. Dosage of transdermal nitroglycerin varied from 0.72 to 5 mg per day for a period of 3 days to 24 weeks. In the acute phase of tendinopathy, 2 studies reported conflicting evidence for pain relief, with the comparison between nitroglycerin and corticosteroid infiltration favoring the latter. In 2 studies, there was limited evidence for the effectiveness of nitroglycerin in improving joint mobility. In the chronic phase, 5 studies assessed pain intensity at rest, with activity, and/or at night. Meta-analysis of the results of 3 of the studies favored nitroglycerin over control for decreasing pain on activities of daily living [odds ratio (OR) 4.44; 95% confidence interval (CI) 2.34-8.40]. When results from the acute studies were included, the positive effects of nitroglycerin on pain intensity remained (OR, 4.86; 95% CI, 2.62-9.02). In chronic tendinopathies, evidence for decreasing pain at rest and during the night was conflicting. Pain duration and sleep-hour duration were not improved. There was limited evidence of improvement effected by transdermal nitroglycerin in range of motion and in local tenderness. Evidence from 3 studies showed an increase in peak muscle force after 24 weeks. All 7 studies reported headache as an adverse event, which resulted in 1 to 9 discontinuations of the intervention. Data from 4 studies found an increase in the incidence of headache with nitroglycerin (OR, 1.73; 95% CI, 1.01-2.97). Data from 3 studies showed no difference in the occurrence of contact dermatitis between nitroglycerin and placebo. Study quality was good (mean score, 23.71/28 points). Most of the studies passed the criteria pertaining to randomization, comparison of baseline characteristics, and appropriate methods of outcome evaluation and analysis. Blinding was infrequent or inadequate.

Topical nitroglycerin relieved pain intensity in activities of daily living among patients with chronic or acute tendinopathies. There was little evidence for effectiveness on other outcomes. The incidence of headache was increased by nitroglycerin.