Ultrasound Neuromodulation (Low-Intensity Focused Ultrasound) to Treat Knee Osteoarthritis Pain: A Randomized, Observer- and Participant-Masked, Sham-Controlled, Human-Subjects Pilot Study

Abstract

Low-intensity focused ultrasound is a non-invasive neuromodulation technique that delivers mechanical forces to a deep location within the body through acoustic pressure waves without affecting tissue between the transducer and focal target. Preliminary studies involving healthy volunteers suggest focused ultrasound reversibly prevents action potential formation similar to a local anesthetic nerve block, but the modality has not been used in patients with existing pain. The current randomized pilot study was undertaken to 1) determine the feasibility and optimize the protocol for a subsequent definitive clinical trial; and 2) monitor for related complications of focused ultrasound when treating knee osteoarthritis pain.

Keywords: analgesia; chronic pain; pain management.

Figure 1

Ultrasound image of the infrapatellar branch of the saphenous nerve (used with permission from Swisher MW, Ball ST, Gonzales FB, Cidambi KR, Trescot AM, Ilfeld BM. A randomized, controlled pilot study using ultrasound‐guided percutaneous cryoneurolysis of the infrapatellar branch of the saphenous nerve for analgesia following total knee arthroplasty. Pain Ther 2022; 11: 1299–1307, PMID: 36018541).

Figure 2

The investigational device used in this pilot study (Resonance, Pegasus Neurotechnology, Melbourne, Victoria, Australia) is comprised of a focused ultrasound transducer, a standard imaging ultrasound, and a coupling device. The transducer is driven by a signal generator and power amplifier. The coupling bladder is a polyurethane/polycarbonate shell which holds both transducers in deionized, degassed water. The investigational device produces clinical effects through the emission of focused ultrasound energy from the transducer: the signal generator sends a signal to the power amplifier, driving the transducer which sends ultrasound waves through the coupling bladder, and finally transcutaneously to the peripheral nerve.

Figure 3

Consolidated Standards of Reporting Trials (CONSORT) diagram.

Figure 4

Effects of low‐intensity focused ultrasound on average, dynamic, and worst/maximum pain level over the previous 24 hours in participants with knee osteoarthritis. Pain severity was measured using a numeric rating scale with 0 equivalent to no pain and 10 being the worst imaginable pain. Data presented is the percentage of baseline at each time point (100% is no change from baseline, >100% is worsening relative to baseline and <100% is improving relative to baseline). Each circle represents one patient, and the mean for each treatment group is denoted with a horizontal line. The data points exceeding 300% for “Average Pain” are presented at the 300% level. Statistics were not applied due to the limited data set.

Figure 5

Effects of low‐intensity focused ultrasound on patient‐centered outcomes. Pain's interference with physical and emotional functioning was measured using the Brief Pain Inventory interference domain. Functional status was measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Data presented is the percentage of baseline at each time point (100% is no change from baseline, >100% is worsening relative to baseline and <100% is improving relative to baseline). Each circle represents one patient, and the mean for each time point is denoted with a horizontal line. Statistics were not applied due to the limited data set.