Low-intensity pulsed ultrasound accelerates and a nonsteroidal anti-inflammatory drug delays knee ligament healing

Am J Sports Med. 2006 Jul;34(7):1094-102. doi: 10.1177/0363546505286139. Epub 2006 Feb 13.


Background: Low-intensity pulsed ultrasound and nonsteroidal anti-inflammatory drugs are used to treat ligament injuries; however, their individual and combined effects are not established.

Hypotheses: Low-intensity pulsed ultrasound accelerates ligament healing, a nonsteroidal anti-inflammatory drug delays healing, and the nonsteroidal anti-inflammatory drug inhibits the beneficial effect of low-intensity pulsed ultrasound.

Study design: Controlled laboratory study.

Methods: Sixty adult rats underwent bilateral transection of their knee medial collateral ligaments. Animals were divided into 2 drug groups and treated 5 d/wk with celecoxib (5 mg/kg) mixed in a vehicle solution (NSAID group) or vehicle alone (VEH group). One to 3 hours after drug administration, all animals were treated with unilateral active low-intensity pulsed ultrasound and contralateral inactive low-intensity pulsed ultrasound. Equal numbers of animals from each drug group were mechanically tested at 2 weeks (n = 14/group), 4 weeks (n = 8/group), and 12 weeks (n = 8/group) after injury.

Results: Ultrasound and drug intervention did not interact to influence ligament mechanical properties at any time point. After 2 weeks of intervention, ligaments treated with active low-intensity pulsed ultrasound were 34.2% stronger, 27.0% stiffer, and could absorb 54.4% more energy before failure than could ligaments treated with inactive low-intensity pulsed ultrasound, whereas ligaments from the NSAID group could absorb 33.3% less energy than could ligaments from the VEH group. There were no ultrasound or drug effects after 4 and 12 weeks of intervention.

Conclusions: Low-intensity pulsed ultrasound accelerated but did not improve ligament healing, whereas the nonsteroidal anti-inflammatory drug delayed but did not impair healing. When used in combination, the beneficial low-intensity pulsed ultrasound effect was cancelled by the detrimental nonsteroidal anti-inflammatory drug effect.

Clinical relevance: Low-intensity pulsed ultrasound after ligament injury may facilitate earlier return to activity, whereas non-steroidal anti-inflammatory drugs may elevate early reinjury risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Biomechanical Phenomena
  • Celecoxib
  • Female
  • Medial Collateral Ligament, Knee / diagnostic imaging
  • Medial Collateral Ligament, Knee / injuries*
  • Pyrazoles / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Sulfonamides / pharmacology*
  • Ultrasonic Therapy / methods*
  • Ultrasonography
  • Wound Healing / drug effects*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Pyrazoles
  • Sulfonamides
  • Celecoxib