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Medication & Treatment

Understanding the Neurobiology of Pain

Author| Ben Bobrow, MD

What is Pain Really?

Pain perception is designed to help us recognize threats to our survival. The perception of pain, of all varieties, is actually created in our brain as a result of stimuli.

Pain can come from a number of different sources:

  • Nerve cells in the skin
  • Perceptions from sensory inputs (hearing, smelling, tasting, etc.)
  • From memories

Pain can be a great motivator. It is designed to make our bodies do something physically, often described as the fight, flight or freeze response.

No two brains are alike, but recent research of brain function has given insight into how many people's brains operate.

How Responding to Injury Works in the Brain

When the brain receives signals that a portion of the body is injured—or is perceived to be injured—it immediately determines how best to respond to the injury. An area in the brain called the amygdala is like our body's smoke detector. The amygdala sends an alarm to the brain when a threat (in this case perceived trauma) is present.

The other areas of the brain that receive the alarm determine how best to respond to the threat (again, the fight, flight or freeze response). The brain considers a number of factors to decide on the best course of action, and sends pain to the body to motivate a response to the perceived threat.

Sometimes, the alarm signal (amygdala) can be activated when a physical experience or threat is not actually occurring.

Here is an example:

A man receives a crushing injury to his right forearm. A signal goes to the amygdala that trauma has occurred, and the brain processes the pain and understands there's trauma. But the damage is so severe, it requires amputation. Months later, the man continues to experience pain as though the injury is still there (a phenomenon known as "phantom limb pain").

How is this possible?

The answer is: pain is a neurobiological process of brain function. In this case, even though the area of the body that was involved in the initial trauma is gone, the part of the brain that senses the limb remains and can be activated by crosstalk from other areas of the brain. The true target of pain relief is ultimately the part of the brain processing the signals.

Pain is best understood as an output from the brain, rather than as input from the body.

Three Types of Pain

Let's discuss pain as an output from the brain by understanding three types of pain:

  1. Acute traumatic pain
  2. Chronic pain
  3. Emotional pain

Acute traumatic pain

This type of pain is well known to us. We experience it frequently in many ways. Hit your finger with a hammer and you experience acute traumatic pain. When we think of acute traumatic pain, we envision the resulting inflammatory process generated by some form of trauma which typically responds to analgesics or anti-inflammatory agents. The inflammatory process model of understanding acute traumatic pain is often extended to the treatment of chronic pain, which, in part, explains our lack of success in many of our treatment approaches to chronic pain. In fact, the strategies employed in the treatment of acute traumatic pain prove counter-productive in chronic pain and actually create more problems! We examine this concept in far more detail and link to more detailed articles.

Chronic pain

This type of pain is also known to many. In fact, it may be the very reason why you are reading this article. But it is complex and less understood, although there is leading research in this area of study.

Emotional pain

Many people react to the word emotional. The emotional aspect of pain is historically laden with negative judgements. All pain perception is associated with an emotional or psychological component. However, when the emotional aspect of pain is considered from a non-judgmental neurobiological perspective it offers a key to better understanding the neurobiological aspect of chronic pain.

Viewing pain as an output from the brain helps us to appreciate the neurobiological aspects of pain. Acute traumatic, chronic and emotional pain can be viewed as overlapping circles, each circle sharing similar response patterns in the brain.

Brain-body pain connection

When I hit my thumb (a traumatic event) with a hammer, specialized nerve cells in the skin send information to my brain via my spinal cord to the various portions of the brain including an area of the mid-brain known as the amygdala. The amygdala senses a threat and signals are sent to areas in the brain that initiate a series of complex neuro-endocrine, neuro-hormonal and neuromuscular changes in the body. At the same time this trauma occurs, literally every other sensory input (taste, smell, hearing, etc.) gets recorded in the brain as an associated memory of the traumatic event. The brain signals a series of physical responses (i.e. inflammation at the site of injury) as well as the perception of pain.

Trauma, of any sort (be it acute, chronic, emotional or a combination thereof) utilizes the same brain mechanism of the amygdala perceiving a threat and sending signals to other areas of the brain to respond.

Chronic pain differs from acute pain in that the perception of chronic pain is experienced over a long period of time. Over the course of time, additional factors come into play regarding how the brain processes the ongoing perceived trauma and how it expresses pain.

Here are some unique facts about chronic pain:

  1. The longer that pain persists, the easier it is to feel it.
  2. You can feel pain from factors unrelated to physical harm.
  3. Your central nervous system adjusts the "volume level" of pain signals sent to your brain.
  4. All pain has a psychological component.
  5. Significant emotional distress is common in chronic pain.

Historically, pain has been viewed with the acute pain model: that an injury to the body results in an inflammatory-type reaction and is treated with pain medications (to block the pain and treat the inflammation) and rest (to allow the injury to subside).

This strategy, however, does not work when pain is sustained for a lengthy time.

In fact it has led to significant societal problems such as opioid addiction, suicide and chronic illness. These disturbing realities led researchers to look for other models to better understand what is involved with pain and to find more effective means to treat chronic pain.

No pain is perceived when the body is in a normal healthy state (often referred to as a state of homeostasis). When pain is perceived it is the result of some traumatic initiating event. However, trauma is not always physical; it can be from an emotional source as well. In other words, prior events that occur in life, such as child neglect or death of a spouse or loved one, can also send signals to the amygdala that the body is not in a state of homeostasis but rather in a threatened state.

Trauma of all sorts gives us pain that affects us many times throughout our lives. Some traumatic events are short-lived and quickly forgotten while others are not. Why is this? To answer this question, let us take a journey of discovery by learning from some of the leading researchers in this area over the last fifteen years or so.

By 2010, Robert Scaer, MD, Neurologist, Chronic Pain Physician and author of the book: The Body Bears the Burden had cared for thousands of patients with chronic pain. He took an interest in a large group of his patients who all experienced car accidents under 10 mph and had significant chronic pain from flexion-extension injuries of the neck (commonly referred to as “whiplash”). He noted several interesting things in this patient population, which consisted of thousands of people, mostly women. All had cognitive complaints such as visual complaints, vertigo and dizziness, an exaggerated startle response, bowel complaints, etc. All of these symptoms were not compatible with the mechanism of trauma associated with the accident.

Dr. Scaer states that he began to take in-depth emotional histories of these patients and found that ninety-five (95) per cent of the patients had histories of child abuse. Additionally he noted that all these patients had the same symptoms and most had post traumatic stress disorder (PTSD). He surmised that symptoms are more an experience than an injury.

Dr. Scaer undertook a comprehensive review of the known literature on trauma and became aware of the work of many scholars in the area, one of whom is Bessel van der Kolk, MD.

Dr. van der Kolk is a professor of psychiatry at Boston University School of Medicine and he is the medical director of the Trauma Center at Justice Resource Institute (JRI) in Brookline, Massachusetts. He is a renowned PTSD researcher and author of multiple books on the subject, including The Body Keeps the Score, which deal extensively with the effect of trauma on the development of the mind, brain, and body. He found that a physiological disruption (disassociation) occurs that results in a destabilization of the body, brain, and specifically the autonomic nervous system.

Dr. van der Kolk noted that trauma is associated with memory mechanisms of the brain; specifically unconscious procedural memory is a critical element in the storage of information during a traumatic event.

Dr. Scaer noted that all the elements of symptoms and sensations experienced by his whiplash patients could be explained by destabilization of the autonomic nervous system and procedural memory.

The autonomic nervous system is the part of the nervous system responsible for control of bodily functions not consciously directed, such as breathing, the heartbeat, and digestive processes. You have likely heard of this system as the “Flight, Flight or Freeze” response of our body in times of stress. It comes from a part of what we call the “animal part of our brain” (the non-thinking part). A commonly used analogy to describe this evolutionary response of the brain cites an analogy of a cave man being chased by a saber tooth tiger; he instinctively needed to employ one of three mechanisms for survival; attack (fight), run away (flight) or play dead (freeze).

Peter A. Levine, PhD has worked in the field of stress and trauma for over 40 years. Since the 1970s, Dr. Levine has explored how animals deal with threats which led to very effective methods of dealing with the effects of trauma overwhelming our nervous systems. He states, “Trauma may begin as acute stress from a perceived life-threat or as the end product of cumulative stress. Both types of stress can seriously impair a person’s ability to function with resilience and ease. Trauma may result from a wide variety of stressors such as accidents, invasive medical procedures, sexual or physical assault, emotional abuse, neglect, war, natural disasters, loss, birth trauma, or the corrosive stressors of ongoing fear and conflict.”1

Levine notes that animals that undergo a freeze response, come out of the freeze response with trembling and shaking, which is a replication of the act that the animal was doing before the freeze response was initiated. The shaking that occurs when the animal comes out of the freeze is a “completion of the escape”; this completion of the escape allows the procedural memory of the trauma to dissipate.

Dr. Scaer’s "whiplash" patients' cognitive and visual complaints—vertigo and dizziness, exaggerated startle response and bowel complaints--were all manifestations of the flight or fight response (sympathetic part of autonomic nervous system). When the event was traumatized, the patients were “helpless” and it resulted in a “freeze” response. Unfortunately, “completion of the escape” from the traumatic event remained in their procedural memory.

Procedural memory (aka Nondeclarative or Implicit) is one part of the brain’s two-part long-term memory system. It represents how our brain remembers physical skills learned through repetition and practice. Eventually, these acts seem second nature to us. Procedural memory involves things like a baby learning to walk, riding a bike, learning to balance on a beam, doing complicated dance moves; such things that are sometimes referred to as “muscle memory.” As the name implies it is the memory of procedures. It is also the memory system for emotional responses and conditioned responses.

The other type of long-term memory utilized by our brain is Declarative memory (aka Explicit memory). This type of memory involves how our brain stores specific personal experiences, events and how we store facts that we learn.

Levine's observation of animals coming out of the freeze response with trembling and shaking as a "completion of the escape" from the procedural memory of the trauma, and Scaer's observation of the freeze response of physical trauma patients led to following conclusion: the completion of the escape extinguishes the memory of the event and if the completion of the escape does not occur, the trauma is stored in unconscious memory.

During the 1890s Russian physiologist Ivan Pavlov became famous for his studies of classical conditioning. Classical conditioning memories are stored in the Procedural Memory System of the brain. Pavlov noticed that his dog would begin to salivate when he entered the room when it was time for it to be fed.

Pavlov initiated an experiment with the dog. He rang a bell when he gave food to his dog and continued to repeat this procedure several times. Then he rang the bell without the food present and it caused an increase in the dog’s salivation.

So the dog had learned an association between the bell and the food and a new behavior was learned. This learned (or conditioned) behavior is called a conditioned response. The neutral stimulus has become a conditioned stimulus.

Pavlov found that for associations to be made, two stimuli have to be presented close together in time (the law of temporal contiguity). If the time between the conditioned stimulus (bell) and unconditioned stimulus (food) is too great, then learning will not occur.
Classical conditioning is how we learn to survive. Not only do we learn how to perform acts with procedural memory for skills, we also learn how to survive using procedural memory for traumatic events. We acquire information that suggests that certain things are threatening to us through conditioned responses.

It is important for us to understand the concept of the Present moment and the Past: Normally, we move along in life in the present moment and we acquire new information by planning and expressing our intentions. In trauma, however, when a person has unconscious procedural memories of trauma all the senses that occurred during the trauma are also recorded. Later if any cue or stimulus occurs (like a smell similar to one that occurred during the initial traumatic event) the PAST memories are perceived by the amygdala as if they are in the PRESENT moment. These unconscious traumatic procedural memories interrupt the process of moving on consciously in life causing the person to become progressively "stuck" in the past.

Why do some become stuck in the past and others do not. This is the core to understanding trauma. It depends on how resilient the person is. What creates resiliency is predominantly determined by the way you experience life in your earliest childhood. Each time you freeze and you don't come out of it the “burden of trauma” goes up and up and up. Each time you are traumatized the more likely you will be traumatized again, and again. As an infant, your brain dissociates—which is a freeze—when you are traumatized—such as through child abuse. The more you disassociate as a child the more likely you are to be traumatized again and again.

Trauma is a negative life event perceived by our brain as life threatening in the face of helplessness. As an individual, we are unique unto ourselves. No one else on this earth has lived our life, nor experienced all of our experiences. No one knows all of the traumas we have endured. Our uniqueness and our relationship to trauma and pain take on shades of meaning; the meaning of the event may be trivial to one person and overwhelming to another person based on their past experiences.

In terms of a person's resiliency, past experiences can compel a person to a greater sense of helplessness or to a greater sense of agency.

Therefore, relatively trivial trauma in the face of helplessness can become profoundly traumatic, but the inverse is also true for some. Going through an event does not necessarily mean that it will be seen by an individual as a profoundly traumatic event.

What we have learned thus far is that pain and trauma are associated. We have also learned that trauma's relationship with pain can be seen on an increasing scale with one end being no physical symptoms and on the other end severe physical symptoms. Let us examine one of the more serious forms of pain associated with trauma, PTSD.

Much research has been done on post traumatic stress disorder or PTSD since the early 1970s. PTSD occurs in some soldiers who have had intensive combat experience. Also, the number of deployments and how much active combat one experiences has a direct relationship to the possibility of the development of symptoms. A second area of importance involves understanding the soldier's psychosocial life before going to war (i.e., the stability of the home situation in which the soldier grew up). Unstable environments in a draftee during the Vietnam era were a major predictor for developing PTSD.

Understanding PTSD is very complex but there are several lessons we can learn immediately. The use of the term PTSD is part of the problem. Exposure to brutal death, dismemberment, and horrific acts of violence affect not only the person who experiences them but all those who surround him or her. No one is immune to the neurobiological impact of such exposure. Clearly some are more resilient than others but all are affected. So viewing the subject matter as a disorder is not helpful. Rather it should be viewed as a neurobiological process when treatment is required.

A full understanding of how the brain and body work is far beyond the scope of this current article, however, it should be noted that neuroscience and geneticists know that chemical compounds exist that turn on or off brain genes.

Consider this explanation from the Lister Hill National Center for Biomedical Communications:

The epigenome is a multitude of chemical compounds that can tell the genome what to do. The human genome is the complete assembly of DNA (deoxyribonucleic acid)—about 3 billion base pairs—that makes each individual unique.

A common type of epigenomic modification is called methylation. Methylation involves attaching small molecules called methyl groups, each consisting of one carbon atom and three hydrogen atoms, to segments of DNA. When methyl groups are added to a particular gene, that gene is turned off or silenced, and no protein is produced from that gene.2

Trauma can be generational. Holocaust studies reveal dramatic demonstrations of how trauma can be generational through the behavior of the parent.3 The children of Holocaust survivors have a twenty percent (20%) increased suicide rate and that is carried on in the next generation of grandchildren.4

The Adverse Childhood Experiences (ACE) Study measuring negative life events on the scale of 1 -10 (severe child abuse to mental illness of a parent) showed that after fifteen years a direct correlation of the negative categories and the person’s susceptibility to major causes of death (addictions, heart disease, suicides, liver disease).5

The autonomic nervous system's sympathetic/parasympathetic cycling is very smooth in the non-stressed person. However, in trauma, an exaggerated cycling occurs with extremes of parasympathetic (freeze) to extremes of the sympathetic (fight/flight) which continues anytime there is a perceived threat.6 That is very bad for the body! In trauma a person is in a severe autonomic abnormal regulation.

Interestingly, all of the so-called psychosomatic diseases have both parasympathetic and sympathetic states (i.e., constipation/diarrhea in irritable bowel for instance). The historic medical approach to illness seeks a “fixed state” of physiology; whereas, in trauma and chronic pain, we are dealing with an oscillating state of physiology.

What has changed in our understanding of chronic pain, emotional pain, and their relationship to traumatic experiences? Most importantly, with the advent of functional magnetic resonance imaging (fMRI) scientists have been able to definitively document neurophysiologic aspects to differing symptom states.

Bessel van der Kolk states that when people remember their trauma their entire frontal lobe (the area of the brain responsible for thinking and figuring things out) goes off line. The speech center located in the frontal lobe (Broca's area) goes off line.

They are struck with speechless terror (dumbfounded). Speechless terror is at the core of trauma and re-telling the traumatic story does not change the physiological response in the brain.

Dr. van der Kolk and his colleagues sought ways to positively affect specific areas of the brain. They found evidence that Yoga for PTSD had far superior results than any drug treatment.7 Why does that happen?

Yale researcher, Judson Brewer, MD, PhD has been able to repeatedly demonstrate, using real-time functional magnetic resonance imaging (fMRI) neurofeedback, that the posterior cingulate area of the brain (which activates when we are craving something or when we are anxious) goes especially quiet when a person meditates.

Furthermore, Brewer was able to teach people who had never meditated to turn off the posterior cingulate by simply paying attention to the sensations from their body.

So van der Kolk sought ways to help people suffering from adverse emotional effects of traumatic events to feel safe in their bodies. He goes on to say, that once a person is traumatized, more traumas attract them. If trauma controls you, you feel victimized and helpless; your resiliency is depleted causing feelings of guilt or shame. The goal is to make people comfortable in the present. The relationship of previous trauma(s) and chronic pain is complicated as it is very difficult for most people to talk about, particularly if family secrets are at the root of a trauma.

Dr. Joseph LeDoux states that the fear center is in the animal portion of the brain. Your thinking part of the brain (prefrontal cortex) has no pathway to the animal center of the brain. You cannot talk yourself out of your emotional brain. The middle brain (orbital prefrontal cortex/ medial prefrontal cortex/ anterior cingulate/ posterior cingulate) represents a sort of Mohawk called the midline structures of the brain. These are the structures of self-perception. These are the only areas of the brain that can access your animal brain.

In a talk given to the California Endowment Center in 2015, van der Kolk stated that he has experienced "four wows" in his professional career regarding treatments for patients suffering from traumatic stress; they are: Prozac, EMDR, yoga and neurofeedback.9

When Prozac was introduced into the market everyone thought that it would be the perfect therapy for patients experiencing traumatic stress. There was, in fact, some improvement but the improvement did not continue.

However, in 1987, Dr. Francine Shapiro discovered EMDR purely by accident. She noticed that while walking in the park she had some upsetting thoughts and feelings that suddenly disappeared. She observed that when she moved her eyes back and forth while thinking of something disturbing the disturbing thoughts went away. She created a procedure called Eye Movement Desensitization and Reprocessing (EMDR) which involves the patient recalling a traumatic thought while focusing and following the therapist’s finger going in a side-to-side motion. She began to use this treatment on clients suffering from PTSD.10 Multiple controlled scientific studies have confirmed that EMDR is one of the more effective tools used to help in the treatment of PTSD.

In 2007, van der Kolk and colleagues reported that EMDR produced substantial and sustained reduction of PTSD and depression in most victims of adult-onset trauma [more than sixty per cent (60%) of patients in the EMDR wing stated they were cured after eight (8) months as opposed to zero (0) patients who were on Prozac].11 EMDR has proven to be an excellent treatment modality in one-time trauma events but not as helpful in childhood trauma.

Dr. David Grand noted while doing EMDR on a patient that physical changes (a fluttering) occurred in patient’s eyes as he moved his finger side to side. Dr. Grand held his finger still at the point where the patient’s eyes fluttered and let the patient focus on his finger. In a short time the eye flutter stopped and the patient felt relief of his traumatic thought. Grand refined the therapy to combine neurofeedback of auditory sounds focused on both hemispheres of the brain. This procedure is known as Brainspotting and it too has become a very helpful tool in treating traumatic memories.12

Trauma therapy is all about finding ways to reset the limbic system and convert procedural memories. Trauma treatments offer a number of exciting opportunities for us to focus on how to treat chronic pain which also has a traumatic procedural memory issue.

The old way of viewing pain simply as the quantifiable result of things like tissue injury and inflammation has evolved into a much more accurate understanding of pain as a multifaceted sensory and emotional experience that is profoundly influenced by our previous experiences and expectations. Recent improvements in neuroimaging (things like functional MRI scans of the brain) have, for the first time, allowed us to identify the various changes in the brain that are associated with both acute and chronic pain. These MRI scans provide clear evidence that even our thinking, such as our attention, anticipation, and particularly fear of pain, dramatically change how we experience pain. Perhaps the most exciting thing is that while it is clear that our emotions greatly impact pain, it is also clear that we can learn how to modify our thinking and tremendously improve pain.

It is helpful to be familiar with the concept of neuroplasticity — the ability of the human nervous system to modify its configuration and function in response to certain stimuli. Most of us are familiar with the brain’s astonishing ability to respond, learn, and reorganize itself. Think about the well-known example of visually impaired people who develop heightened abilities of hearing and fine sensory discrimination when using their hands. Neuroplasticity may be an attempt by the nervous system to adapt to injury in a positive way. But in the case of pain, neuroplasticity appears to be maladaptive.

Remarkably, it has been shown that explicit areas of the brain, known as the pain matrix, are triggered in response to pain. The pain matrix is believed to include several parts of the cortex (outer portion) of the brain as well as other areas called the thalamus, basal ganglia, and particularly the amygdala which deals with processing emotions. These areas are involved in distinguishing dangerous and harmless stimuli. Over time, when bombarded with pain signals, these areas of the brain change.

We know that neuroplasticity also occurs with pain and is associated with a host of functional, anatomical, and chemical changes to the brain. While it is not yet entirely clear why, when, or to whom these changes occur, they have been shown to be strongly linked to the presence of pain. When these changes take place, the result can be over-sensitization where previously normal signals are interpreted as arising from tissue damage.

Pain is not merely an expression of sensory input but is a multidimensional experience taking into account attention and expectations resulting from past and learned experiences.

However, these discoveries offer reasons for hope. The first reason is that, although it may sound odd, neuroplasticity is by nature malleable, meaning that although nervous system changes can occur, they are not irreversible.

The further reason for hope is that the latest research affords us with a much better appreciation of the role of psychological factors in pain and the enormous potential for improvement.

There is no room for the obsolete view that pain is either real or psychological.

Cognitive and emotional processes strongly engage brain and spinal cord pathways that are directly involved in altering the responsiveness of pain pathways. Psychological features impact neuroplasticity and thus directly transform the pain experience.

The role of mood and thought processes in altering neuroplasticity builds additional backing for the role of psychological interventions in treating pain, not only as a way of being able to deal with pain, but as an effective option for relieving pain.

We are here to help, schedule an appointment today with one of our licensed therapists and begin to take back you life!


References

  1. Somatic Experiencing Trauma Institute accessed 11/30/2016.
  2. Apr 1, 2016 Lister Hill National Center for Biomedical Communications U.S. National Library of Medicine National Institutes of Health Department of Health & Human Services; published Nov. 22, 2016.
  3. Kellerman, N. (2001). Psychopathology in children of Holocaust survivors: A review of the research literature. Israel Journal of Psychiatry and Related Sciences, 38, 36-46.
  4. The New Traumatology and the Trauma Spectrum, Part 2, Robert Scaer, MD.
  5. Vincent J Felitti MD, FACP, Robert F Anda MD, MS, Dale Nordenberg MD, David F Williamson MS, PhD, Alison M Spitz MS, MPH, Valerie Edwards BA, Mary P Koss PhD, James S Marks MD, MPH (1998). Relationship of Childhood Abuse and Household Dysfunction to Many of the Leading Causes of Death in Adults : The Adverse Childhood Experiences (ACE) Study, Amer J of Prev Med, 14(4):245-258.
  6. Antleman, S., Caggiula, A., Gersohon, S., Edwards, D., Austin, M., Kiss, S., Kocan, D. (1997). Stressor-induced oscillation: A possible model of the bidirectional symptoms of PTSD, New York Academy of Sciences, 21:296-305.
  7. Ann. N.Y. Acad. Sci. xxxx: 1–17 (2006). C 2006 New York Academy of Sciences. doi: 10.1196/annals.1364.022.
  8. LeDoux, J. (2003) Cellular and Molecular Neurobiology,  The Emotional Brain, Fear and the Amygdala; Oct 2003;23(4/5)727-738.
  9. The Body Keeps the Score: Brain, Mind, and Body in Healing of Trauma published may 22, 2015, accessed 11/20/16.
  10. Maiberger Institute: How was EMDR Therapy Discovered? accessed 11/30/16.
  11. van der Kolk, BA, Spinazzola J, Blaustein ME, Hopper JW, Hopper EK, Korn DL, Simpson WB (2007) A randomized clinical trial of eye movement desensitization and reprocessing (EMDR), fluoxetine, and pill placebo in the treatment of posttraumatic stress disorder: treatment effects and long-term maintenance. J Clin Psychiatry, Jan;68(1)37-46.
  12. Brainspotting accessed 11/30/16.