The Frontal Cortex

The Emotions of Chronic Pain

Imagine you are a doctor, and a patient comes into your office with a serious case of back pain. You begin by performing all the standard diagnostic tests, including an MRI and X-ray. Then, you perform an extensive interview. You ask about his psychological history, and rate his level of depression, fear and anxiety. You also assess him for a variety of risk factors that tend to correlate with back pain, including his job satisfaction, and whether or not he is involved in pertinent litigation. After this extensive medical evaluation, you try to predict how intense his back pain is and how long it will last. Unfortunately, your verdict won’t be very useful. According to a 2005 paper in Pain, all of these parameters can only explain about 25 percent of the individual variance in chronic back pain.

But what if you tried a different diagnostic strategy? Instead of looking at the patient’s back and asking him all sorts of personal questions, let’s say you just study his brain. You measure a few brain chemicals, and then image his cortex in an fMRI machine. It turns out that this approach is much more effective. You are now able to predict about 80 percent of the variance associated with chronic back pain. Your judgments about his clinical condition have become significantly more reliable.

That, at least, is the message of a 2006 paper out of the Apkarian lab of Northwestern. The scientists, in a series of simple and well-controlled experiments, located the neural underpinnings of chronic back pain. The scientists found that chronic pain – unlike acute pain – activated brain regions typically associated with negative emotions and response conflict, like the mPFC and rostral ACC. It’s as if the chronic pain had stopped being sensory in nature, and was instead built into the emotional brain. That’s why it never went away.

But last week, Apkarian’s lab came out with a promising paper in Pain that might help suppress those negative emotions. The researchers looked at D-Cycloserine, a drug originally designed for TB infections, but which has also been used to treat social phobias. (It’s pretty amazing how many of our brain drugs are sheer accidents.) According to Apkarian’s rodent studies, rats with chronic pain were living pain free lives after thirty days of pharmaceutical treatment. Apkarian is hoping to begin a clinical trial with chronic back pain patients later this year. “When we do this in a clinical trial, we expect people to say I still have the pain, but it’s not bothering me anymore,” Apkarian says. “We think they will have a physical awareness of the pain, but its emotional consequences will have decreased.”

Obviously, there’s a vast different between curing chronic pain in rats and humans. But I think trying to reduce the emotional component of chronic pain in the cortex is a fascinating and novel approach. Given the dismal success rate of more conventional medical approaches to chronic pain (i.e., surgery and opiate painkillers), it’s time we start looking for new alternatives.


  1. #1 km
    June 14, 2007

    While an interesting point, there is the risk of doctors going back to the old “it’s all in your head”. Chronic pain is a very serious problem, and, while it may be in part due to certain chemicals, still starts somewhere.

    It’s true, though, that chronic pain sort of builds up to take on a life of its own. I have chronic neuropathic pain, though, while chronic, it is not permanent. When the pain comes, it can take control of all thoughts and hang out for hours or days. Fortunately, some meds do work for this type of pain (I’ve found clonazepam to be best, though gabapentin is very good too, but I couldn’t handle the side effects.) In my experience, you need to nip the pain in the bud before it builds up, because then it takes over the emotions. I can imagine that people who have no respite are always at that level.

  2. #2 Jonah
    June 14, 2007

    Thanks for sharing your experience, and I’m glad you’ve found a treatment that helps. My only comment is that saying that chronic pain is “all in our head” doesn’t make it any less real. The pain is always real, regardless of whether it has a specific bodily source or is predominately a result of misfirings in the central nervous system. Pain, after all, is a fundamentally subjective experience.

  3. #3 km
    June 14, 2007

    Yes, pain is subjective, and that’s probably the hardest thing about it, medically. I recall when I was young being told I had a high pain threshhold – it was a doctor who told me that after I was taken to the hospital with acute appendicits. Ah, would that were still true.

    But I’ve been in contact with lots of people who have chronic pain, notably headaches, and the problem is that subjective is just a few inches away from imaginary in the minds of many medical professionals (not to mention familary members). It certainly would be good if they could find an answer.

    Meanwhile, relaxation always helps, which rejoins what you’ve pointed out in your article. And, one good way to relax is to read Proust. 🙂

  4. #4 Aaron
    June 15, 2007

    Would shutting off or limiting the emotional response/pathways prevent a beneficial cascade of neurotransmitters and hormones?
    Cortisol? Cannabinoids? etc?
    Which leads me to the question… Why does it become chronic? Why doesn’t all pain become chronic? Of course the longer the pain is present the more “worn-in” the emotional/chronic pain pathways become (like a highway vs. a country road). Though its likely that the emotional portion of chronic pain is beneficial (and possibly “broken” in those that it continues) in alleviating the actual problem.
    Good study and important for everyone to realize that this route for treatment is not going to be the cure-all for pain, acute or chronic.

  5. #5 Paul
    June 27, 2007

    Orthopedic Development Corporation’s President and CEO, James Doulgeris, said in an affidavit in a federal court case (Case Number: 1:07-CV-00363) in North Carolina that he had never engaged in business in that state, had not gone there to recruit a sales executive or “otherwise traveled there.” However, a securities watchdog website which posted an investigative report on ODC on June 8, has copies of e-mails that appear to disprove those assertions. The e-mails include flight numbers and times, and the names and locations of the hotels in which he allegedly stayed.

    Winston-Salem, NC (PRWEB) June 25, 2007 — Dan Grayson, former Vice President of TruFUSE Sales for minSURG Corporation, a wholly owned subsidiary of Orthopedic Development Corporation (ODC), Clearwater, Florida, announced today that he has filed litigation against those entities and James Doulgeris, the company’s President and CEO on May 8, 2007 at 9:14 am in the United States District Court for the Middle District of North Carolina (Case Number: 1:07-CV-00363, Grayson vs. Orthopedic Development Corporation, minSURG Corporation and James Doulgeris). The suit alleges Fraudulent Inducement to Contract and Breach of Contract.

    “This should simply be a case of who’s telling the truth and who has the evidence to support it,” Grayson stated. “I am confident that when it comes down to that, my story will be vindicated in a court of law. I’m spending my own money to fight this battle on behalf of patients, surgeons, insurers and the medical community. I’m appealing for help from any and all applicable regulatory agencies to stop medical device companies that make claims and market products or procedures prior to having documented clinical studies. In my opinion, the FDA, SEC, FBI, OIG, Medicare, American Medical Association and other federal and state regulatory agencies should take a serious look at those companies.”

    Grayson continued, “There are other questions that have gone unaddressed by Doulgeris and other company officers and directors, such as; Where are their clinical studies? Why won’t they release any of the results from random surgeons? Why did world-famous surgeon, Jurgen Harms, M.D., state in an email to, ‘Without biomechanical test and clinical outcome studies, I don’t see a chance to use this product clinically?” (Note: Dr. Harms is considered to be one of the world’s noted authorities on spine surgical procedures.)

    ODC, in a press release on June 21, 2007 found on, accused Grayson, an investor and three other company employees of conducting a defamatory anonymous e-mail campaign aimed at the companies and its officers and directors. The press release also went on to state that minSURG has ‘shipped enough TruFUSE to treat over 1,500 spinal levels’, ‘over 80 orthopedic and neurospine surgeons have used TruFUSE’ and ‘more than 60 hospitals have evaluated, and approved TruFUSE for use in their hospitals’.

    “It’s been my experience that medical device companies don’t gauge the success of their product by the number of the devices ‘shipped’ or necessarily the number of surgeons using the product. Instead, they focus on the patients and provide unbiased multi-center studies and definitive proof that the product works prior to releasing it for use.” Grayson elaborated, “I really don’t think that patients or surgeons care about how many products were ‘shipped’ when it comes to efficacy, safety and surgical outcomes. Any time I have spoken to surgeons about ‘clinical success’, they have never mentioned ‘shipping’ as even being a criteria of how well a product works. I sure would like to see the documentation pertaining to the alleged evaluations from ‘more than 60’ hospitals.”

    The same ODC press release stated, ‘The board of directors created a special committee comprised of its independent directors earlier this year, which worked in conjunction with the legal counsel to assess the veracity of the allegations set forth in the anonymous e-mails and, later, by the defendants directly after they were exposed. The board committee determined that the company, its remaining officers, employees, directors and partners have acted responsibly, with integrity and have conducted the company’s business with the highest professional standards’.

    “Where in this statement, made by ODC, did they actually address the ‘veracity of the allegations’ made by the alleged anonymous e-mails,” Grayson noted. “I believe they are evading questions, realize they have been exposed and are trying to take the focus away from the real issues.”

    In a document, referenced in an article on (a securities watchdog website that is covering this story), Doulgeris states, “A review of the first 500 cases has prompted us to increase our estimate of expected failures….” The article features several links to documents that exhibit the company’s claims and the ensuing litigation.

    “Where is the alleged documentation of those 500 cases Doulgeris claims to have reviewed by January 31, 2007?”, Grayson commented. “That would mean 500 folders on 500 patients with thousands of pages of documentation, including a significant number of computed tomography scans (CT scans).” A CT scan is considered by many surgeons to be the gold standard to analyze fusion and determine if the allograft dowel did not come loose.

    LifeLink Tissue Bank, a Tampa, not-for-profit, manufactures the devices, according to an article in the St. Petersburg Times on June 12, 2007.

    In addition to the article on, other articles regarding this litigation have recently appeared in The St. Petersburg Times, Florida’s largest circulation newspaper and The New York Times.

    # # #

  6. #6 Nani
    July 12, 2007

    This study seems to confirm what I’ve come across with a number of my massage therapy clients. I’ve found that chronic pain is in a sense “in the head” but is very real. As I see it, the pain of the initial injury, usually very acute and traumatic, gets deeply grooved in the nervous system and sets up a a faulty feedback loop. The positive feedback loop most of us experience is ‘injury has healed, now can resume normal function etc.” But with very acute/traumatic injuries, the intensity, long duration and emotional duress of the pain creates an persistent “broken record” effect — a deeply ingrained somatic-emotional memory. For most of these clients, a combo. of meds and massage or other bodywork helps them immensely, not only to relieve stress which exacerbates the pain conditions but also to help the body relearn what feeling good feels like. What angers me is that most of these clients have been treated pretty dismissively by their doctors.

  7. #7 Mariel
    July 12, 2007

    I went to a PT today, who successfully treated my husband in the past. He said that I hurt everywhere. It’s good to have a human being recognize this.

    I have the genetic disease porphyria and probably MS as well. I talk to hundreds of people in chronic pain every day on the internet. Their pain is not there just because of grooves in the nervous system, although those grooves are there. It’s from constantly being triggered into a porphyric reaction. Many things trigger porphyrins to increase if one has a certain defect in the heme synthesis pathway: these triggers include many pharmaceuticals, many environmental toxins, stress, endogenous toxins such as estrogen, and a some foods which are high in phytoestrogens or sulfur. In other words, the environment these people live in gives a strong chance of triggering.

    So far, no way out. There are some European studies to produce the missing enzyme in one type, with hope of producing the other missing enzymes in other types of porphyria. In the USA, little going on. Maybe in a decade some of us will be helped to get rid of chronic pain.

    For now, helping young porphs to avoid triggers is our only hope as a subclass of humanity.

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