Is pain really an output of the brain?

Posted on June 11, 2018


(Last Updated On: June 11, 2018)

In the last ten years or so a community has popped up called the pain science community. This group has steadfastly championed what is called a top down approach of addressing pain, rather than a bottom up one.

For example, your knee hurts. Rather than an approach most of us are familiar with, where we examine the knee, X Ray, MRI, strengthen muscles, etc., the pain science world starts with the brain. Did you have an old injury which now, due to fear, you are guarding the knee? Making you more likely to experience pain than you otherwise would? Or you’re stressed about life. This stress makes you experience more pain. So the stress needs to be addressed.

To be clear, the people doing the actual research are not then saying “ignore the knee.” This is despite many who follow but don’t actually read the research pushing tenets to the extreme of “MRIs are worthless, orthopedists know nothing about pain, muscles have nothing to do with pain” and on it goes.

Lorimer Moseley, perhaps the current leader of pain science:

“A common misinterpretation of my work is that I think that there is no point thinking about primary nociceptive input in people with pain. I do not think this and I do not think I would ever have said this. What I do think is that there is compelling evidence that the relationship between pain and tissue damage is seldom simple and is sometimes very tenuous indeed.”


All that’s really going on is people like Moseley are trying to get a better understanding of why something like a lack of sleep might increase your knee pain, and acknowleding that, along with other elements, as a factor. There is no pain science revolution though. People have known this stuff for as long as they’ve had a human body. A shitty day at work makes everything feel shittier. We get it.

But there is one hell of a new(er) study on pain-

The “pain matrix” in pain free individuals

I’ve never read such a short study so many times!

“Human functional imaging provides a correlative picture of brain activity during pain. A particular set of central nervous system structures (eg, the anterior cingulate cortex, thalamus, and insula) consistently respond to transient nociceptive stimuli causing pain. Activation of this so-called pain matrix or pain signature has been related to perceived pain intensity, both within and between individuals, and is now considered a candidate biomarker for pain in medicolegal settings and a tool for drug discovery.”

Take your right hand. Have something push on it, which after some amount of pressure, would be pain causing. Do this and the brain will light up in certain areas, which can be seen with a functional MRI. This is the “pain matrix” or “pain signature.” The fact these are in quotes, even in the study’s title, should tell you something…

How can you prove the brain’s lighting up response is due to pain? How do you know the lighting up isn’t only from your right hand being touched? That’s what this study is getting at.

Genetic anomalies are a great way to study these things. Like people who congenitally can’t experience pain. Yes, this study found a couple of those people!

Take these people, compare them to normal people…and there is no difference in how much the brain lights up, or where it lights up. As the authors then say,

“These observations reinforce the need for caution in using pain matrix responses for diagnosis or drug discovery and corroborate evidence that reported correlations between neuroimaging data and perceived pain have largely relied on non-pain-specific activities.”

Other evidence such as this:

“Physical pain can be clearly distinguished from other states of distress. In recent years, however, the notion that social distress is experienced as physically painful has permeated the scientific literature and popular media. This conclusion is based on the overlap of brain regions that respond to nociceptive input and sociocultural distress. Here we challenge the assumption that underlies this conclusion – that physical pain can be easily inferred from a particular pattern of activated brain regions – by showing that patterns of activation commonly presumed to constitute the ‘pain matrix’ are largely unspecific to pain.”

A lot has been made about the brain’s response to pain with functional MRIs. A LOT. Turns out we didn’t know what we were even measuring!

-> It’s worth noting the immediate above study is from 2013. And this one of the same vein is from 2010. The pain science world -again, the non-researchers- has all kinds of research they regularly cite. They have not acknowledged plenty of research disputing their citations.

But how do these people not experience pain? What’s different about them? The brain is still responding to the sensory input of touch, but not pain. What’s causing that?

They have a genetic mutation at gene SCN9A, which disrupts proper function of sodium channel 1.7. We won’t go into the weeds on that. Suffice to say sodium channels are how a lot of actions happen in the body. You want to make a muscle contract? Sodium channels are used to make that happen. There are different channels much like there are different ways to get into New York City. You can take the bridge; you could take the tunnel.

We do need to know a bit more about these Na (for sodium) v (for voltage) 1.7 channels. Lets look at this paper:

Mutations in Sodium Channel Gene SCN9A and the Pain Perception Disorders

Which tells us Nav 1.7 channels:

“are highly expressed in sensory neurons of the dorsal roots, trigeminal ganglion, and sympathetic neurons ganglia, mainly in the nociceptors.”

“Scientists believe that the role of NaV1.7 is to contribute to nerve hyperexcitability.”

When incorporating the genetic mutation:

“SCN9A gene is coding the 𝛼 subunit of NaV1.7 and is primarily expressed in neurons of the dorsal root ganglia, sympathetic neurons ganglia, Swann cells, and neuroendocrine cells.”

Ok, a bunch of various structures were just referenced. Bare with me as we break them down briefly. We don’t need to memorize the below, we just need to catch the theme (all from Wikipedia and Merriam Webster):

-sensory neurons

“are nerve cells that transmit sensory information (sight, sound, feeling, etc.). They are activated by sensory input, and send projections to other elements of the nervous system, ultimately conveying sensory information to the brain or spinal cord.”

-dorsal roots

“the one of the two roots of a spinal nerve that passes dorsally to the spinal cord and consists of sensory fibers.”

-sympathetic neurons ganglia

“are the ganglia of the sympathetic nervous system. They deliver information to the body about stress and impending danger, and are responsible for the familiar fight-or-flight response. They contain approximately 20,000–30,000 nerve cell bodies and are located close to and on either side of the spinal cord in long chains.”


“is a sensory nerve cell that responds to damaging or potentially damaging stimuli by sending signals to the spinal cord and brain.”

-swann cells

“are the principal glia of the peripheral nervous system.”

-trigeminal ganglion

“is a sensory ganglion of the trigeminal nerve (CN V) that occupies a cavity (Meckel’s cave) in the dura mater”

Since it was mentioned a bunch, a ganglion

is a nerve cell cluster or a group of nerve cell bodieslocated in the autonomic nervous system. Ganglia house the cell bodies of afferent nerves.

The autonomic nervous system

“is a division of the peripheral nervous system that influences the function of internal organs”

I hope it is clear, from current knowledge, a dysfunction of sodium channel 1.7 is a dysfunction going TO the brain. Not from the brain to the body. From the body to the brain.

Afferent, not efferent:



In an ideal world, would you change this person’s brain, or the amount of Nav1.7 sodium channels?

“We’re also looking at more common causes of pain, where we don’t have mutations. If we get an injury to our peripheral nerves, for instance, our traumatized nerve cells make too many Nav1.7 sodium channels. These play an important role in burn injuries as well,”

Sodium Channels Offer Path to Personalized Pain Management

To reiterate,

“Nav1.7 is present at the endings of pain-sensing nerves, the nociceptors, close to the region where the impulse is initiated.”


Congenital insensitivity to pain is considered a form of peripheral neuropathy because it affects the peripheral nervous system

NIH Genetics Home Reference

The pain science community has been berating us that nociception is not necessary for pain. That pain is an output of the brain. Yet if a person does not have a specific to the brain input, they can’t feel pain!

Phantom limb pain is constantly referenced by pain science people. “Look! No limb! No nociception but pain is felt!” It needs to be considered that a lack of input from body to brain may cause pain too. Particularly when the person was born with the limb. (You don’t hear about phantom limb pain in congenital amputees for a reason!) Hence, give someone mirror therapy, and their phantom limb pain can disappear. They all of a sudden received a to the brain input. The periphery was changed; not the brain.

Next, I get the impression people generalize phantom limb pain to all pain as “If we didn’t have a brain, then the person wouldn’t have pain in the limb. But you can not have a limb and still have pain. So the focus should be on the brain.” But that’s like saying you can’t have a heart beat without a brain, so if the heart has trouble beating, we should look at the brain and make the heart secondary. No, we know in the context of heart issues, the heart is likely the problem. That doesn’t mean we ignore the brain with a heart attack patient. Stress, psychological factors, of course they’re relevant. Nobody in cardiology is saying ignore them just like nobody in orthopedics is.

With a broken control tower a plane can’t take off. But with a broken wing the plane can’t take off either.

Pain will end up being viewed like cancer. Your cancer is different than his cancer is different than her cancer.

  • You mainly need surgery to remove the tumor as none of the cancer has spread
  • He needs a more global treatment like chemotherapy as the cancer has spread
  • She needs gene therapy to address the mutation she was born with
  • They need follow up drugs because the cancer has a high rate of recurrence
  • And on it goes

Your pain is different than his pain is different than her pain.

  • You need surgery to address the torn ACL
  • He needs to lose weight as being 300 pounds makes everything feel like crap, including his self esteem
  • She needs vitamin D
  • They need to understand arthritis does not automatically mean knee replacement
  • And on it goes

The whole debate is silly. It’s not bottom up; it’s not top down. It’s all around.

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Posted in: Miscellaneous, Pain