Background & Aims
Knee Osteoarthritis (OA) is the most common form of OA, which affects 500 million adults worldwide, with pain being the primary symptom. Central pain mechanisms such as central sensitization and inefficient central pain inhibition are major contributors to knee OA pain. However, current treatments for symptoms in knee OA do not fully consider these issues. Diminished parasympathetic function has been reported in knee OA and is thought to contribute to central pain mechanisms. Therefore, stimulating the vagus nerve, the primary nerve of the parasympathetic nervous system, may improve central pain mechanisms and, thus, knee pain by readjusting parasympathetic activity. Transcutaneous vagus nerve stimulation (tVNS) applied to the ear has improved parasympathetic function in other conditions and may improve central pain mechanisms and pain in knee OA. However, tVNS has not yet been used in knee OA. Thus, we tested the feasibility and preliminary efficacy of tVNS for people with knee OA.
Methods
This was a pilot study with a 60-minute tVNS. We recorded intervention completion rate and any side effects related to tVNS. The following outcomes were assessed immediately before, immediately after, and 15 minutes after tVNS: knee pain during a 20-meter walk, using a 0-10 scale; pressure pain threshold (PPT), with lower values reflecting greater central pain sensitivity; temporal summation (TS), pain ratings after a 10-stimulus using a weighted probe subtracted from baseline pain ratings, with positive values indicating central sensitization; conditioned pain modulation (CPM), a ratio of post-conditioning PPT to pre-conditioning PPT, with ratios < 1.0 indicating inefficient central pain inhibition; and High-frequency (HF) heart rate variability (cm2/Hz), obtained from a validated smartphone application, with higher values reflecting greater parasympathetic activity. We evaluated whether outcome measures changed after tVNS using linear mixed models, adjusting for age, sex, and BMI.
Results
We included 30 people with knee OA (mean age 55 years, 67% female, 83% Hispanic, mean BMI 33). All participants fully completed the 60-minute tVNS intervention without breaks during the intervention. 28 out of 30 (93%) participants experienced no side effects or adverse events and completed the intervention without difficulty. One experienced slight and momentary nausea, while another participant experienced momentary dizziness. Both symptoms presented immediately post-intervention and resolved within a few minutes. Compared to baseline, knee pain was reduced by 1.27 (95% CI, -1.74, -0.80, p<0.001) immediately after and by 1.87 (-2.33, -1.40, p<0.001) 15 minutes after tVNS; CPM improved by a ratio of 0.11 (0.04, 0.19, p=0.004) and 0.07 (-0.01, 0.15, p=0.07); and HF improved by 213.29 (-0.38.09, 426.96, p=0.06) and 234.17 (20.49, 447.84, p=0.04), respectively. PPT and TS were not significantly changed after tVNS.
Conclusions
We demonstrated the safety and feasibility of a 60-minute tVNS as a pain-relieving treatment for people with knee OA. We found that the tVNS intervention improved knee pain, on average, beyond the minimal clinically important improvement. This suggests that improvement of knee pain might be derived from improvement of parasympathetic activity and/or central pain mechanisms as no local therapy was applied. Our pilot study has provided important preliminary insights into developing novel non-pharmacological interventions with innovative targets to ameliorate knee pain in people with knee OA. A future study is needed to confirm the effects of tVNS compared with a control group in larger clinical trials with more robust and clinically applicable methodologies.
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Presenting Author
Kosaku Aoyagi
Poster Authors
Kosaku Aoyagi
PhD
The University of Texas at El Paso
Lead Author
Elias Rivas
University of Texas at El Paso
Lead Author
Roxanna Shababi
University of Texas at El Paso
Lead Author
Levi Johnson
University of Texas at El Paso
Lead Author
Robert Edwards
PhD
Brigham & Women's Hospital/Harvard Medical School
Lead Author
Michael LaValley
Boston University
Lead Author
Julia Lechuga
University of Texas at El Paso
Lead Author
Tuhina Neogi
Boston Univ School of Medicine
Lead Author
Topics
- Treatment/Management: Interventional Therapies – Neuromodulation