Can We Forget About Chronic Pain?

By Ann Marie Gaudon, PNN Columnist

I recently came across a clinical report which describe two patients with a lengthy history of chronic pain severe enough to warrant opiate therapy. Both patients experienced sudden memory loss and forgot about their pain – literally.

Central sensitization is a process known to occur in the spinal cord and brain where if short-term acute pain is allowed to persist, then changes occur within the central nervous system which can lead to chronic or intractable pain.

That’s what happened to me. I have a diagnosis of a visceral pain syndrome, as opposed to a progressive pain condition. I experienced one vicious organ assault and after more than 30 years of it being healed, I remain in pain.

Other patients who have experienced painful trauma may relive painful episodes that evoke recurring memories -- they experience their pain over and over again. That is a classic symptom of post-traumatic stress disorder (PTSD). Think of a war veteran or survivor of sexual violence.

Either way, neurophysiologic changes which relate to learning, memory and pain can result in a maladaptive learning process which leaves one in chronic pain. These intricacies happen outside of conscious awareness. We are not aware of or in control of this dysfunctional process while it is occurring within our brain and spinal cord circuits.

Here is an overview of the two patients discussed in the report:

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Patient #1

The first patient is a 47-year old female with complicated health problems. She had undergone multiple surgeries and treatment modalities for gastric ulcers, endometriosis, thyroid cancer, hypothyroidism, seizure disorder, malnutrition and chronic abdominal pain over 10 years.

Her pain was managed with high doses of opiate medications in various forms, including intravenous, transdermal and oral. During a complex 12-month hospital stay, she had at least five seizures and suffered memory loss so severe she could not remember her entire stay in the hospital.

She did eventually become fully alert and oriented to the present, but she no longer complained of her pain symptoms and no longer demonstrated a need for consistent pain medication.

Six months after discharge, the patient was living at home in stable condition and only occasionally using tramadol. She reported her symptoms as minimal and 1-2 on the pain scale. She still has no memory of many aspects of her long hospitalization.

Patient #2

A 57-year old male was described as a “highly functioning architect” with a 10-year history of low back and right extremity pain. He had undergone many unsuccessful treatments for pain, including surgery, and was being admitted to hospital to have an intrathecal pump surgically implanted for pain control. He was taking no less than nine medications for pain including high doses of opiate therapy.

Initially after the pump was placed, he reported having a partial reduction of pain in his leg. However, in the next six months he was requesting higher doses of intrathecal as well as oral opiates.

One month after this, the patient was in a minor motor vehicle accident where he did not lose consciousness, but inexplicably had partial memory loss. His physicians felt the accident was not the cause, as the memory loss symptoms occurred long afterward. The cause of the amnesia was unknown and tests including a brain MRI showed as normal.

The patient could not remember the names of his doctors, where he lived, what type of work he did, or why he had a pain pump implanted. He was weaned off opiates without any complaint of increased pain and subsequently had the pump removed at his request.

Eight months later, this patient was found minimally responsive in his home. It is not known what occurred, but there was a suspicion that he had fallen and incurred a head injury. The patient experienced profound memory loss, with no memory of who he was, his family members or his back pain.

His pain medications were discontinued with no complaint of pain, but he required placement in a long-term care home due to severe amnesia. Over the next two years, this patient regained partial memory, along with some back and leg pain. He has not requested or required opiate therapy.

Emotions, Pain and Memory

We know pain perception can be caused by nociceptive stimuli, yet we also know that emotional and psychological factors can increase our perception of pain. A complex play of nerve fibers which transmit messages to the brain and spinal cord suggest there is a relationship between emotions, pain and memory. The best evidence that memory plays a role in pain is that of phantom limb pain.

The two cases presented here suggest that memory may influence the perception of pain, and that amnesia can be accompanied by a loss of or significant reduction of pain in the absence of any physical factors.

Treatments that reduce “pain memories” in the brain and spinal cord, along with a focus on preventing pain to reduce or eliminate these memories, may someday have a more widespread role in the management of chronic pain. To have a treatment or ability to effectively erase a maladaptive pain memory leaves me with just three words:

Count me in.

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Ann Marie Gaudon is a registered social worker and psychotherapist in the Waterloo region of Ontario, Canada with a specialty in chronic pain management. 

Ann Marie has been a chronic pain patient for over 30 years and works part-time as her health allows. For more information about her counseling services, visit her website.

This column is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Discovery of Brain Protein Could Lead to New Chronic Pain Treatments

By Pat Anson, PNN Editor

Researchers have identified a protein in the brain that appears to play a prominent role in the maintenance of long-term pain -- a discovery that could lead to new treatments that stop short-term acute pain from progressing to chronic pain.

The protein RGS4 (Regulator of G protein signaling 4) is found in brain circuits that process pathological pain, mood and motivation.

"Our research reveals that RGS4 actions contribute to the transition from acute and sub-acute pain to pathological pain states and to the maintenance of pain," says Venetia Zachariou, PhD, a professor in The Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai in New York City.

"Because chronic pain states affect numerous neurochemical processes and single-target drugs are unlikely to work, it's exciting to have discovered a multifunctional protein that can be targeted to disrupt the maintenance of pain."

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In studies on genetically modified mice, Zachariou and her colleagues found that genetic inactivation of RGS4 did not affect acute pain, but it promoted recovery from nerve injuries, chemotherapy-induced neuropathy and peripheral inflammation. Mice lacking RGS4 developed all the expected symptoms of a nerve injury, but recovered within 3 weeks and returned to physical activity.

The transition from acute to chronic pain is accompanied by numerous adaptations in immune, glial and neuronal cells, many of which are still not well understood. Chronic pain patients experience a number of debilitating symptoms besides pain, such as sensory deficits, depression and loss of motivation

Researchers believe future drugs that target RGS4 could prevent acute pain from transitioning to chronic pain. Currently available medications for chronic pain only treat the symptoms – not the underlying condition – and have major side effects.

Dr. Zachariou's laboratory is conducting further investigation into the actions of RGS4 in the spinal cord and mood-regulating areas of the brain to better understand the mechanism by which the protein affects sensory and pain symptoms.

Their findings are published online in The Journal of Neuroscience.

Chronic Pain Accelerates Dementia

By Dr. Lynn Webster, PNN Columnist

In 2017, JAMA Internal Medicine published a study that found older people with chronic pain experience faster declines in memory and are more likely to develop dementia.  While prior research had shown a link between chronic pain and brain damage, this was one of the first studies to specifically suggest that chronic pain can cause dementia.

The authors reported that people aged 60 and over with persistent pain experienced a 9.2% more rapid decline in memory score when compared to people of the same age without chronic pain. This means that people with chronic pain may experience more difficulty in managing their finances, medications and social connections.

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Dementia is a chronic condition of the brain that involves memory, personality and judgment. It is not a disease; it is a symptom of one or more diseases.

There are many types of dementia. Alzheimer’s disease is considered to be the most common.

Dementia usually worsens over time if the underlying disease remains static or progresses, as is the case with many chronic pain conditions.

There are an estimated 20 million Americans with high impact (the most severe) chronic pain who may be experiencing accelerated decline in cognition due to their pain. The amount of dementia appears to be associated with the severity and duration of chronic pain. Undertreated or untreated chronic pain may accelerate dementia.

Chronic pain affects an even larger percentage of elderly adults (one in three) than the general population. Since the prevalence of chronic pain increases with age, the probability of experiencing dementia increases as well. However, the reasons for that go beyond aging itself.

Seniors are more likely to take multiple medications that can contribute to mental confusion. On average, elderly people take five or more prescriptions. They may also use over-the-counter medications, which adds to potential drug-associated mental compromise.

Opioids, in particular, have been implicated in cognitive impairment. However, a study published in 2016 suggests there is no difference in cognitive decline between people on opioids and those on nonsteroidal anti-inflammatory drugs. The study's implication is that pain, not opioids, leads to cognitive impairment.

Brain Fog

Chronic pain appears to affect the function and structure of the hippocampus. This is the region of the brain that involves learning, memory, and emotional processing.

One explanation for the mental decline associated with chronic pain is that various areas of the brain compete for attention. Attentional impairment compromises memory by diverting attention to the areas of the brain processing pain. In effect, the brain is multi-tasking and favoring the processing of pain over cognition. This may, in part, explain the clinical phrase “brain fog.”

The Australian Broadcasting Company's "All in the Mind" website explains that pain damages the brain in several ways, including a change in the size of the thalamus and a decrease in the amount of a neurotransmitter (gamma-aminobutyric acid) the brain produces. In other words, chronic pain changes the brain structurally and functionally.

The prefrontal cortex is the part of the brain responsible for executive functions, such as cognition, social behavior, personality, and decision-making. It is also the part of the brain that modulates pain.

According to "All in the Mind," some researchers believe that chronic pain decreases the volume of the prefrontal cortex. Over time, brains damaged by pain lose the ability to handle pain — along with some of the personality attributes that make us who we are.

Brain Damage Can Be Reversed

The good news is that the brain damage caused by chronic pain can be reversed, at least to some extent. Unfortunately, the elderly are less likely to recover from dementia caused by chronic pain as compared with younger patients.

If pain is adequately treated, the brain may be able to regain its ability to function normally. A 2009 study of patients with chronic pain due to hip osteoarthritis showed reversal of brain changes when their pain was adequately treated. 

People who don’t have their acute pain managed are more likely to develop chronic pain. It is postulated that the changes in the brain that occur with chronic pain begin with the onset of acute pain. There is also some evidence that an individual’s genes may influence who is at greatest risk for developing brain damage from chronic pain and who is least likely to recover from it. 

Many people have criticized the concept of assessing pain as the 5th vital sign, and have called it a contributing factor for the opioid crisis. As I have said, pain may not be a vital sign, but it is vital that we assess it. Asking patients about their pain is critical to providing interventions that can mitigate the consequences of undertreated pain, including dementia. 

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Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is author of the award-winning book, The Painful Truth,” and co-producer of the documentary,It Hurts Until You Die.” You can find him on Twitter: @LynnRWebsterMD. 

The information in this column is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Pain Companion: When Pain Hijacks Your Brain

By Sarah Anne Shockley, Columnist

I had a great inspiration for this article a couple of weeks ago and immediately forgot what it was. I exhausted myself, uselessly racking my brain for the idea I’d had. What was it I thought was so perfect to write for Pain News Network?

Several days went by with me trying to find the elusive idea. I couldn’t even figure out what it related to. It was as if it had completely left the universe and was utterly irretrievable. Gone without a trace.

Ever feel like that?

Studies have shown that chronic pain affects the brain, but most of us living with chronic pain don’t need researchers to tell us that. We live with brains that don’t seem to be firing on all cylinders every day. I don’t know if there is an official term for it, so I’m just calling it “Pain Brain.”

In this and my next column, I’ll discuss some of the ways in which Pain Brain affects our ability to cogitate -- and some practical ways I’ve found to live with it a little more gracefully and even to coax the brain back online.

Dealing with Blank Spaces        

Do you find yourself in the middle of a sentence and can’t remember what you were talking about? Sometimes can’t come up with the words for even the most common items like chair, book, pen

We worry that we might be getting Alzheimer’s and sometimes find ourselves very embarrassed when, in the midst of telling someone something important, our brains simply turn off.

We’re left with our mouths hanging open in mid-sentence, whatever we were just talking about an utter mystery to us. We draw a complete blank. Sometimes it’s just a word, but often it’s the whole concept. Just gone. This can be extremely disconcerting.                                    

I find, particularly when I’m tired, that I’m creating sentences with a whole lot of blank spaces in them. “Can you hand me the... the... the... the... you know, I mean, uh... the… the... the.....” You’ve probably done this too.            

Stop. Breathe. Relax. Laugh. Choose another word. Or just let it go and carry on without that word or even that idea. It’s not that your brain is dying, you’re in pain.            

I’ve found that it’s usually not all that helpful to exert a lot of energy to try and recapture the word I lost. I’ve found that my efforts usually don’t make a bit of difference. I can’t conjure up that exact word or thought no matter how hard I try - and I just wear myself out and get flustered.                   

Pushing your brain to get back into gear creates tension, and you don’t need any more of that. Trying to find the exact word leaves a longer silence in your conversation, and you get the deer-in-the-headlights look, and that’s when you begin to feel uncomfortable and embarrassed. You want to say, I’m not really stupid or senile or easily distracted, I used to be able to converse with the best of them!                   

Instead, just move on with the conversation. Usually, sooner or later, the words you need pop back in. Sometimes much later. Sometimes in the middle of the night. But that’s okay. If we can just be easy with it, it’s not that big of a deal. It’s usually more disconcerting for us than the person we’re talking with.

Dealing with Brain Freeze

There are times, however, when it’s more than a particular word that’s missing. For me, it’s often a total brain freeze. Everything comes to a screeching halt, usually in mid-sentence. I have no idea what I was just saying, what the topic of the conversation was, or what direction I was headed in.                  

It’s pretty strange, because you don’t lose the power of speech, you just have no idea what you’re talking about anymore. It’s like the part of your brain dealing with that specific subject goes on a coffee break in the middle of a sentence, leaving you kind of stunned by its complete lack of presence.

For friends and family members, you can make up a code word or phrase for when you’re feeling disconnected from your own brain. I often just say, Sorry, my brain just stopped. It’s short and to the point, and they’ve learned what it means. They either remind me of what we were talking about, or we move onto something else.                   

For other people who don’t know your situation, and if you find yourself embarrassed by your own stupefaction, you might try just changing the topic. It’s really strange, but the brain seems to be able to go somewhere else and work relatively well, just not where you wanted it to go at the moment.

You can also distract other people’s attention from your sudden silence by asking them a direct question such as, What were you saying a moment ago? Or simply, What do you think? If they have something they have to respond to, it usually diverts their attention from your blank stare.

If you refer to what they were saying indirectly, without having to remember exactly what it was they actually said, they will often fill in the blanks for you and help you back on track -- without you having to explain that your brain just stopped.

Living with Pain Brain can be challenging, but in my experience, those of us who struggle with it notice the blank spaces and lost words much more than anyone we’re conversing with.    

In my next column, we’ll talk about memory loss and lowered capacity to cogitate. I’ll have some suggestions for working with them as well.                                

Sarah Anne Shockley suffers from Thoracic Outlet Syndrome, a painful condition that affects the nerves and arteries in the upper chest. Sarah is the author of The Pain Companion: Everyday Wisdom for Living With and Moving Beyond Chronic Pain.

 Sarah also writes for her blog, The Pain Companion.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represent the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

How Chronic Pain Changes Mood and Motivation

By Pat Anson, Editor

Researchers in California have found the first biological evidence that chronic pain alters regions in the brain that regulate mood and motivation -- raising the risk of depression, anxiety and substance abuse.

In animal studies at UCLA and UC Irvine, researchers found that brain inflammation in rodents that was caused by chronic nerve pain led to accelerated growth and activation of immune cells called microglia. Those cells trigger chemical signals within the brain that restrict the release of dopamine, a neurotransmitter that helps control the brain's reward and pleasure centers.

"For over 20 years, scientists have been trying to unlock the mechanisms at work that connect opioid use, pain relief, depression and addiction," said Catherine Cahill, associate professor of anesthesiology & perioperative care at UCI, Christopher Evans of UCLA's Brain Research Institute. "Our findings represent a paradigm shift which has broad implications that are not restricted to the problem of pain and may translate to other disorders."

The study also revealed why opioid drugs such as morphine and cocaine may lose their effectiveness as animals transition from acute pain to chronic pain. Cahill and her colleagues learned that opioids fail to stimulate a dopamine response in mice and rats, resulting in impaired reward-motivated behavior.

Treating the rodents with a long-acting antibiotic called minocycline inhibited microglial activation, and restored dopamine release and reward-motivated behavior. That finding suggests that a similar approach could be used in treating chronic pain in humans.

"Our findings demonstrate that a peripheral nerve injury causes activated microglia within reward circuitry that result in disruption of dopaminergic signaling and reward behavior. These results have broad implications that are not restricted to the problem of pain, but are also relevant to affective disorders associated with disruption of reward circuitry," the study found.

The results of the five-year study appear online in the Journal of Neuroscience.

Cahill and her research team are now trying to establish that pain-derived changes in human brain circuitry can account for mood disorders.

"We have a drug compound that has the potential to normalize reward-like behavior," she said, "and subsequent clinical research could then employ imaging studies to identify how the same disruption in reward circuitry found in rodents occurs in chronic pain patients."

Researchers Say Brain Processes Pain Emotionally

By Pat Anson, Editor

Many chronic pain sufferers resent being told their pain is “all in your head” or that they’re being too emotional about their pain.

But tests conducted by German researchers suggest that the human brain begins to shift from sensory to emotional processing of pain after just a few minutes of painful stimuli.

Scientists at Technische Universität München (TUM) in Munich enrolled 41 people in a study to measure brain activity as they were exposed to painful heat stimulation of a hand. Participants wore a cap with 64 electrodes that measured nerve cell activity in the brain throughout the experiment. The electroencephalograms (EEGs) made it possible to pinpoint which nerve cells respond to pain.

Participants were then given painful heat stimuli to the hand for ten minutes, with the intensity of the heat varying throughout the experiment. The test subjects were asked to continuously assess the level of their pain on a scale of one to a hundred with the other hand using a slider.

"We were absolutely amazed by the results. After just a few minutes, the subjective perception of pain changed. For example, the subjects felt changes in pain when the objective stimulus remained unchanged. The sensation of pain became detached from the objective stimulus after just a few minutes," said Markus Ploner, MD, a professor for human pain research at the TUM School of Medicine.

Previous studies have shown that brief pain stimulation is predominantly processed by sensory areas of the brain that process signals from nerves in the skin. However, in the heat experiment with longer-lasting pain, the EEGs showed that emotional areas of the brain became active.

"If pain persists over a prolonged period of time, the associated brain activity shows that it changes from a pure perception process to a more emotional process. This realization is extremely interesting for the diagnosis and treatment of chronic pain where pain persists for months and years," explained Ploner.

A second experiment showed that it is not just the duration, but also the anticipation of pain that affects perception. Twenty test subjects were given different intensities of painful laser pulses on two areas of the back of the hand. The participants then verbally rated how strong they perceived the pain to be.

In a second round of testing, the subjects were again given the same stimuli, but this time with two creams applied to both hand areas. Although neither cream contained an analgesic, the subjects were told that one of the creams had a pain-relieving effect.

Researchers found the cream had a placebo effect.

"The subjects assessed the pain on the skin area with the allegedly pain-relieving cream as significantly lower than on the other area of skin," said Ploner.

In addition to feeling less pain, the EEGs showed that nerve cells triggered a different pattern of brain activity.

"Our results show how differently our brain processes the same pain stimuli. Systematically mapping and better understanding this complex neurological phenomenon of 'pain' in the brain is a big challenge, but is absolutely essential for improving therapeutic options for pain patients," added Ploner.