Two articles on PainSci cite Koopman 2016: 1. Zapped! Does TENS work for pain? 2. Chronic, Subtle, Systemic Inflammation
PainSci commentary on Koopman 2016: ?This page is one of thousands in the PainScience.com bibliography. It is not a general article: it is focused on a single scientific paper, and it may provide only just enough context for the summary to make sense. Links to other papers and more general information are provided wherever possible.
Vagus nerve stimulation sure sounds great (maybe a little too great): stimulate your vagus nerve with an implant, et voila, less systemic inflammation. There’s broad biological plausibility here, but almost no evidence — this idea hinges only on the results of this one study so far. Koopman et al. tested it on humans and reported that “these results establish that vagus nerve stimulation targeting the inflammatory reflex modulates TNF production and reduces inflammation in humans.”
Established, eh? Not without replication! That’s overconfident for sure — this needs replication before celebration.
All kinds of data hijinks could be hiding in a study this technical. My main concern is the use of the word “significantly” in the abstract, without any details (effect size in particular). All too often that wording, without clarification, means there was a statistically significant but clinically trivial result. With many treatment trials I can go digging for the effect size to confirm, but not here, the reading is too difficult for me to form any meaningful impression without spending an hour, and even then it might not be clear. And even if the paper does indicate a clinically meaningful result it’s still got “too good to be true” written all over it and may well prove to be difficult to reproduce.
But it’s a genuinely interesting topic, I think.
~ Paul Ingraham
original abstract †Abstracts here may not perfectly match originals, for a variety of technical and practical reasons. Some abstacts are truncated for my purposes here, if they are particularly long-winded and unhelpful. I occasionally add clarifying notes. And I make some minor corrections.
Rheumatoid arthritis (RA) is a heterogeneous, prevalent, chronic autoimmune disease characterized by painful swollen joints and significant disabilities. Symptomatic relief can be achieved in up to 50% of patients using biological agents that inhibit tumor necrosis factor (TNF) or other mechanisms of action, but there are no universally effective therapies. Recent advances in basic and preclinical science reveal that reflex neural circuits inhibit the production of cytokines and inflammation in animal models. One well-characterized cytokine-inhibiting mechanism, termed the "inflammatory reflex," is dependent upon vagus nerve signals that inhibit cytokine production and attenuate experimental arthritis severity in mice and rats. It previously was unknown whether directly stimulating the inflammatory reflex in humans inhibits TNF production. Here we show that an implantable vagus nerve-stimulating device in epilepsy patients inhibits peripheral blood production of TNF, IL-1β, and IL-6. Vagus nerve stimulation (up to four times daily) in RA patients significantly inhibited TNF production for up to 84 d. Moreover, RA disease severity, as measured by standardized clinical composite scores, improved significantly. Together, these results establish that vagus nerve stimulation targeting the inflammatory reflex modulates TNF production and reduces inflammation in humans. These findings suggest that it is possible to use mechanism-based neuromodulating devices in the experimental therapy of RA and possibly other autoimmune and autoinflammatory diseases.
Specifically regarding Koopman 2016:
This page is part of the PainScience BIBLIOGRAPHY, which contains plain language summaries of thousands of scientific papers & others sources. It’s like a highly specialized blog. A few highlights:
- Photobiomodulation therapy is not better than placebo in patients with chronic nonspecific low back pain: a randomised placebo-controlled trial. Guimarães 2021 Pain.
- No effect of creatine monohydrate supplementation on inflammatory and cartilage degradation biomarkers in individuals with knee osteoarthritis. Cornish 2018 Nutr Res.
- The CANBACK trial: a randomised, controlled clinical trial of oral cannabidiol for people presenting to the emergency department with acute low back pain. Bebee 2021 Med J Aust.
- Relationships Between Sleep Quality and Pain-Related Factors for People with Chronic Low Back Pain: Tests of Reciprocal and Time of Day Effects. Gerhart 2017 Ann Behav Med.
- Modulation in the elastic properties of gastrocnemius muscle heads in individuals with plantar fasciitis and its relationship with pain. Zhou 2020 Sci Rep.