Have scientists discovered inflammation’s master switch in the vagus?

The summary of a new study about inflammation control starts with some strange words: “The body-brain axis is emerging as a principal conductor of organismal physiology.” I have quibbles:

• Is there some other kind of physiology? My inner editor is rolling his eyes. Science should never be written like you’re trying to sound like the kid with the best vocabulary in class. Not even in the fanciest journals like this one: “the” journal Nature.

• No one really talks about the “body-brain axis,” any more than we would talk about the “engine-wheels axis.”

• What exactly is “emerging” about the fact that the brain is the boss of our biology? I thought this had been basic knowledge about how animals work for decades now. Neuroimmunology is not exactly brand new. But okay… “emerging”!

The sprawling vagus nerve

Notice that the many vagal branches almost create a partial map of the viscera, especially the GI tract. Also notice how it’s very clearly a pair of nerves descending from the brain, not “the” (singular) vagus nerve.

I’m sure Jin et al. are highlighting our continuing education in how much the brain tinkers with our physiology, which is certainly more than physiologists thought when they were experimenting with LSD in their bell-bottoms at Woodstock.

Important vagus news! Extra, extra!

This is vagus nerve research, and any big vagus news is basically guaranteed to make headines. In this case, the headlines about Jin et al. are declaring the discovery of a “master regulator” of inflammation throughout the body, found in the headwaters of the vagus nerve, a huge nerve linking brain to organs.

The vagus nerve is a hype magnet. Every scrap of related science is exploited to justify vagus “reset” and “toning” therapies and thinking (see Vagus nerve hype and hope). This study will pour gasoline on that bonfire.

The cool part

Don’t get me wrong: this is interesting science. Jin et al. found “distinct populations of vagal neurons” that “tightly modulate the course of the peripheral immune response.”

And they know that because they muted those neurons to produce “out-of-control inflammatory responses” around the body, and then they flipped the script and suppressed inflammation broadly by stimulating those neurons. That strongly confirms the job description for those neurons: they limit inflammation.

In mice. Sure, there’s a chance it’s also a people thing. But mice lie.

Mice lie

“Mice lie and monkeys exaggerate” in research. And they lie a lot, even about brain stem neurology. I know this may be hard to believe, but animals don’t all do neuroimmunology exactly the same way! So this is not much of a “discovery” until confirmed in humans.

The theoretical potential here is obvious: if specific neurons can suppress inflammation systemically, maybe someday we can do that with an implant in humans with chronic pain, autoimmune diseases, and so on.

Yet more “maybe useful someday” science.

Unfortunately, the potential is not the only thing that’s obvious.

Mice can be excellent models for human physiology, but they are also infamously misleading. Hence the charming research expression: “mice lie & monkeys exaggerate.”

Obvious problems

Even if this master switch for inflammation actually works this way in mice (this is one study), and then even if it works the same way in Homo sapiens as it does in Mus musculus, there are still two major concerns, probably both deal-breakers:

• It’s not like we already have amazing methods for tickling specific groups of neurons. You can do a lot of stuff with mice experimentally that just isn’t medically practical in humans, even if it would be useful in principle. But would it even be useful in principle?
• As ever, the most basic problem with relieving pain control is that pain is a deeply integrated part of our biology, and it’s almost impossible to stop it without also stopping other things you need. “Reducing inflammation” will always sound great to pain patients, but it’s synonymous with “immune suppression”… which doesn’t sound quite so good, does it? Be careful what you wish for. We can already suppress inflammation/immunity very nicely with drugs (steroids), but it’s one of the best examples of a double-edged sword in medicine. Steroids are crazy good at reducing inflammation, but the downsides are equally crazy. When it’s the lesser of evils, it’s a marvel. But for most people there’s nothing “lesser” about the evils of immunosuppression.