It turns out, it really is all in your head.

I’ve been thinking about Dune a lot lately. I think I might be the only person in the world who prefers the bizarre and grotesque David Lynch movie version to the elegantly crafted Villeneuve oeuvre, including David Lynch himself. We lost a real artist with his passing, and a rewatch of Twin Peaks is very much on my to do list for this winter.

But back to Dune, because one of the pivotal scenes in the novel and both movie versions is one where young Paul Atreides is tested by the Machiavellian Bene Gesserits. He has to put his hand in a box. Inside the box? Pain. Ever increasing pain. He must keep his hand in the box, despite all his instincts telling him to pull it out to prove his fundamental humanity — his ability to exercise control over his own brain.

Because, as the Reverend Mother points out after the ordeal, his hand is unharmed. The pain is a fabrication — pain by nerve induction, she says. There is no physical damage. It’s all in his mind.

And of course, that’s true of all pain isn’t it? It’s not your toe that hurts when you stub it. Signals are sent from your toe, up a nerve to your spinal cord, up another nerve to your thalamus, and then onto the cortex to give it context, emotion, intensity, reality. If that chain is broken — pain simply does not occur. It’s all in your mind.

That’s what makes pain so difficult to treat. It is fundamentally subjective. I’ve had patients with wounds that would make me scream for my mother who sat stoically silent while we worked on them. And I’ve had those who… well… seemed like they were hamming it up a bit.

But right now our best tool to get a window into someone’s level of pain is a tool like this. A pain scale. How much does it hurt?

“You think you can dissect me with this blunt little tool?” - Hannibal Lecter.

And given that the answer may lead us to prescribe some ice, or some Tylenol, or some morphine — well, the answers aren’t always reliable. Or even consistent.

To quantify pain, to put a non-subjective number on it, we’d need to read someone’s mind.

Well… maybe we can.

Pain is on my mind this week thanks to this study, appearing in JAMA Neurology, from David Seminowicz and colleagues at the University of Western Ontario. Their goal was to use non-invasive brain studies — in this case electroencephalogram (EEG) and transcranial magnetic stimulation (TMS) to interrogate the level of pain someone is feeling.

Source: Chowdhury et al. JAMA Neurology 2025

To do that, they enrolled 150 healthy participants with no history of chronic pain.

Then, they needed to hurt them. And they needed to hurt them all in a very standard way. Their model here was to inject a substance called nerve growth factor into the right masseter muscle. That’s the muscle right in front of your ear that does a lot of the chewing. I mean, honestly — this is so gom jabbar, right?

When you inject nerve growth factor into a muscle, it hurts. And not just for a moment. It hurts for about 4 weeks — it’s a model of acute pain that turns into chronic pain. I am quite curious how much these 150 volunteers were paid to participate in this study. And more curious if they felt it was adequate after the fact.

Before we get to the brain, let’s talk about the effect this injection had on pain levels.

The authors used a statistical technique called growth mixture modeling to identify two types of people in their cohort — those for whom this injection causes a lot of pain — and those for whom it’s not so bad. Their scores, over time, are shown here.

The yellow group — people who experienced more pain — were in a lot of pain. You can see their scores were around the top, 10 or so, for the first few days of the study, before coming back down a few weeks later.

The blue group tolerated it better. It still hurt, they reported, but it wasn’t the worst.

So the question at hand is — can you tell who is who from the brain alone.

And the answer is yes. Almost perfectly in fact.

The authors identified two brain biomarkers — measurements — that could be made that would predict quite well what group an individual belonged to. Via EEG, they looked at the sensorimotor peak alpha frequency — this is a measure of the rate of oscillation of brain waves, basically. And they found that slower peak alpha frequency predicted more pain.

Transcranial magnetic stimulation might not be as familiar as an EEG, but it’s seeing increasing use. TMS uses a targeted magnetic field to sort of “poke” the brain — give it a little stimulus in a very specific area. You then can see how quickly that stimulus propagates to other areas. In the case of this study, they looked at something called corticomotor excitability — how quickly a signal from the cortex can get to the part of the brain that controls muscles. Slower signaling? More pain.

Combining these two metrics — peak alpha frequency and corticomotor excitability — was all the researchers needed to predict who would belong to which group, the high pain or the low pain group. And it worked with about 90% weighted accuracy.

But there’s more to the study than that. The thing that really blew my mind was the effect of including psychological information about the participants.

There’s a standard survey called the “pain catastrophizing scale” that helps to quantify the psychological impact of pain. Certain individuals may tend to ruminate on pain more, or have more anxiety about the idea of pain, or feel helpless to manage pain.

But here’s the thing — the inclusion of those scores didn’t improve upon the brain measures at all. Like — to predict how much pain someone is going to report, knowing about their psychology was essentially useless in this study — provided you know about the electrical signals in their brain.

Which is just sort of an amazing way to think about and understand pain, and honestly people’s complaints about pain. It’s not that some people react worse to the same level of pain, it’s that some people’s brains process those signals differently.

Psychology is a slave to biology, not the other way around.

There’s one last twist to the study that I want to leave you with. And that is that one of the two metrics assessed — the peak alpha frequency — was measured before the injection into the masseter muscle. Alone, that measurement couldn’t perfectly predict who would have more pain — but it was still pretty good.

What that means is that this study has opened the door to two new ways to think about and deal with pain. First — a way to predict the severity of pain before you experience it. Think of this as a tool to be used before elective surgery, for example, to help physicians and patients prepare for post-operative pain and manage therapy. And second — to quantify the degree of pain a patient may be feeling acutely, in order to better dose pain medication.

There’s a dark version of this, of course. There’s a world where we stop listening to patients’ complaints and just strap something on their head that spits out how much oxycodone they should get. I don’t want that world, and I’m sure you don’t either. But there are cases where this will help — particularly those cases where the cause of pain isn’t obvious (like fibromyalgia), and doctors might minimize the symptoms when the patient describes them. Well, maybe tools like this will prove what patients have been telling us all along. And when doctors dismissively say “well, it’s all in your head”. Patients can accurately say — indeed it is. Treat it please.

A version of this commentary first appeared on Medscape.com.

Methods Man Blog

The Promise of Quantifying Pain

It turns out, it really is all in your head.

The Methods Man