Note to the ReaderThe following article discusses material of a potentially upsetting nature. While the narrative details are fictional, the ideas and themes—both scientific and personal—are real. Information regarding resources for those in crisis can be found at the end of this article.

by Emily Orwell
figures by Sean Wilson

I’m having one of those days. You know, the type where I accidentally slice my finger open while chopping vegetables.

Even as I rinse and band-aid my finger, my body and brain are working together to create the feeling of pain. My nervous system is made up of neurons that “talk” to each other primarily though chemicals called neurotransmitters, or alternatively, through electrical signals (Figure 1). Specialized neurons in my skin detect the damage and send “warning signals” which travel through my spinal cord, to more neurons, and finally to the brain. The processing of pain in the brain is complex, and multiple regions are involved in forming the sensation of a knife cut. This kind of acute pain is unpleasant, but it’s an evolutionary necessity: pain sends important signals to warn against dangerous or harmful situations.

Eventually, dinner is ready, so I grab my meal and start a movie on Netflix. Film, like so many other art forms, can elicit emotions of happiness and exhilaration—or, less pleasantly, fear, anger, and sadness. Processing of emotions, positive or negative, has long been attributed to the brain’s limbic system, which is nestled in the inner part of our brain and consists of at least a dozen smaller structures. Incidentally, the limbic system also enables us to sense and react to our environment through pain. Like physical pain, emotions have evolutionary importance. For instance, fear helps us avoid danger. More generally, emotions are powerful motivators of our actions and reinforce behaviors that help maintain an orderly society.

At the most basic level, pain and emotions come from the same neuron-messaging system. For this to happen properly, the close to 100 billion neurons in my body are organized into intricate neural circuits (Figure 1). Neurons rarely, if ever, work in isolation: a single neuron can physically connect to and receive incoming signals from up to 10,000 neurons while also sending outgoing signals to another 10,000 neurons.

Considering the staggering number of neurons involved, our neural circuitry works remarkably well nearly all the time. And when it works the way it’s supposed to, pain or sadness eventually go away.

Figure 1: The nervous system is responsible for feeling pain and emotions. Left: When the body experiences injury, neurons (nerve cells) detect the damage. A series of neurons relays this message through the spinal cord and up to the brain. The brain then translates the message into “pain.” This relay-messaging system is based on one neuron sending molecules known as neurotransmitters to the next neuron in line (inset). Neurotransmitters are packaged into compartments known as vesicles (circles) to regulate when and how they are released. Pain is interpreted in various parts of the brain, including the limbic system, which is also responsible for processing emotions. Right: A highly stylized, abstract depiction of how neural circuits are organized. Neural circuits coordinate the close to 100 billion neurons in the human body. When there are problems with the circuit connections and organization, conditions such as chronic pain and depression can arise. Circuits are highly complex, comprising different neuron types (indicated by arrowheads vs. blunt connectors), and different functions (indicated by colors).

Chronic pain and depression: consequences of a nervous system gone awry

The immediate acute pain from my cut is a direct consequence of my injury. If my nervous system is on the right track, the pain should recede once the injury heals. But this time around, something goes wrong. My nervous system gets derailed, and months after my knife wound has completely healed, I still experience a frustrating mystery pain in my hand.

This makes me one of an estimated 25.3 million American adults who experience chronic pain (Figure 2). This means that close to 1 in 10 of your friends and colleagues is affected. For some sufferers, the pain is easily attributed to an injury or an illness, but for others, the reasons for the pain are unclear. In my case, the cause is obviously the knife wound, but the persistence is mystifying. A more severe version of this phenomenon is unfortunately common among amputees: it’s estimated that 40-80% of amputees experience serious phantom limb pain in the body part that has been removed. In such cases, chronic pain does not stem from obvious physical damage but reflects a nervous system that cannot “turn off” the pain signal.

At the same time as I’m experiencing pain, I find another similarly constant and unwanted companion: chronic depression. Depression is a complicated illness, and no two sufferers experience the same thing. It is commonly likened to sadness but can encompass other feelings, such as emptiness and lethargy. When I experience normal sadness, I can identify a specific cause, and I know that I will feel better eventually. Depression is different. It can start suddenly and, unlike normal emotions, can linger indefinitely (Figure 2).

Measuring the comorbidity, or simultaneous co-occurrence, of pain and depression is challenging, so there are no definitive numbers on how many suffer from both conditions. Nevertheless, studies generally agree that compared to the general populace, people who suffer from one are more likely to have the other. Some suggest that 30-50% of Americans experiencing chronic pain will also experience depression, while other estimates go as high as 85%. Similarly, it’s estimated that, on average, 65% of those suffering from depression also experience pain. Regardless of the exact numbers, there are undoubtedly millions who go to bed every night hurting in body and mind, and who wake up to the same every day.

Figure 2: The facts on chronic pain and depression and their social and economic costs.

Two rotten apples from the same tree

Why did I get unlucky twice and experience both pain and depression? As unfair as it feels, scientific studies suggest that something in my biology predisposes me to having both conditions. Pain and depression can unleash a vicious cycle in which each condition continually worsens the other. Furthermore, these conditions are similar at a biological level: under normal conditions, our senses and emotions are managed by many of the same brain regions. When things do go wrong, be it pain or depression, similar or even identical changes in the brain are often observed.

Neurotransmitters are a key part of the nervous system, as these molecules are like the “words” that are “spoken” by neurons to send a message — like feelings of pain or sadness. Of the many flavors of neurotransmitters, the group known as monoamines has been strongly associated with both pain and depression. It’s thought that both chronic pain and depression can result when levels of these key monoamines are too low (Figure 3).

Figure 3: The potential effects of chronic pain and depression on the nervous system. Under normal circumstances (left), there are adequate levels of neurotransmitters, which are the molecules that help carry messages between neurons (left inset). In patients with chronic pain and/or depression (right), there can be reductions in the amount of brain matter (in the region indicated in purple). Important molecules, including neurotransmitters, can also be reduced in quantity (right inset). Antidepressant medications are prescribed to try to restore the normal state in patients with chronic pain, depression, or both.

This idea that pain and depression are both caused by a neurotransmitter imbalance is strengthened by ample clinical studies of antidepressant medications. Antidepressants combat neurotransmitter deficiency (Figure 3), and they can be effective against both depression and chronic pain. Examples of antidepressants with proven benefits in pain management are tricyclic and SSRI antidepressants, which increase the amount of monoamines that can actively send messages around the nervous system. Intriguingly, opioids, a traditional pain treatment, may also relieve symptoms of depression but are not generally recommended due to their highly addictive nature.

Both chronic pain and depression can change the physical structure of the brain itself. For instance, reduction in the amount of brain tissue in the pre-frontal cortex, which is part of the limbic system, has been observed for both those suffering from chronic back pain and from depression (Figure 3). Unlike the changes to neurotransmitters, the decrease in brain tissue is likely an effect, rather than cause, of chronic pain or depression, but nonetheless demonstrates the similarities between the two conditions.

While researchers have identified the above links (and many more) between chronic pain and depression, as a scientist myself I understand that these are highly complex conditions and that solving them fully is a monumental task. Still, scientists are making amazing advances every day, and I remain hopeful that there will be better solutions in my lifetime.

Invisible illnesses are still real

For now, managing chronic conditions can be difficult, exhausting, and even socially alienating. Many of my acquaintances assure me that I “look so good,” and like many with invisible illnesses, I struggle to explain that looks can be deceiving. Because I don’t appear to be sick, it’s awkward to ask for assistance or accommodations. My pain, compounded by symptoms like fatigue and nausea, greatly hampers my ability to do things I used to take for granted, like carry groceries or walk across a parking lot. The people I actually confide in never assume that they can “diagnose” me: I value the people who believe my side of the story, on my own health, instead of their assumptions.

Invisible illnesses, unsurprisingly, can be difficult to detect and treat, and having more than one condition adds another layer of complexity. For people who have chronic pain and depression, it’s estimated that the depression gets missed 60% of the time. Some of the reasons for this oversight include that patients are more likely to report physical than mental symptoms, and that medical professionals are inclined to attribute reported symptoms to solely physical causes. Because the pain symptoms “mask” the potential depression diagnosis, patients and their healthcare providers end up focusing on only one half of the problem. This is problematic because patients may have less success treating chronic pain if they are not correctly diagnosed for mood disorders.

Always higher and always forward, towards a happier and pain-free future

People say that in life, only death and taxes are certain. But sometimes I worry if I should be adding pain and depression to my list. A critical challenge is that there is no one-size-fits-all solution for chronic pain or depression, individually or together.

Initially, I try prescription antidepressants. While they can be very effective for some people, they can also have severe and disruptive side effects, including but not limited to nausea, migraines, and weight gain. They can also stop working over time or never work in the first place. I don’t respond well to medications, but luckily, I do experience improvement from another widely recommended method: exercise. Exercise has well-documented benefits for both chronic pain and depression, and may even rival medications in effectiveness.

I also look into cognitive behavioral therapy (CBT). In this well-established strategy, therapists train patients to avoid negative thoughts and emphasize positive thinking. CBT may sound simple, but clinical outcomes show that CBT is a very promising treatment for pain and depression. According to brain imaging studies, CBT can actually make measurable changes to the neural circuits and brain activities that are involved in both chronic depression and pain, .

Many more options exist, which is great but also daunting. Because there’s no one guaranteed solution, finding the right treatment requires the tenacity to try many things and accept frequent disappointment. I know I’m supposed to “hang in there,” but as anyone else with a chronic condition can attest, doing so is much easier said than done.

For all those who have similar conditions, I believe we must press on while giving ourselves permission to feel disheartened at times. Living with chronic diseases is hard enough–there’s no need to pressure ourselves to be strong all the time. It’s not an easy situation, so it’s OK to feel overwhelmed. In such moments, I’m immeasurably grateful for my close friends and family, and I urge everyone to not only pursue medical options but to also find that confidant who is patient, faithful, and listens without judgment. If you are fortunate enough to be healthy, perhaps you can be that person for someone else.

Though it’s slow progress, every day I’m getting closer to where I want to be. In the meantime, I’m being a bit more careful about where I put my fingers when I’m cooking.

Emily Orwell is the pen name of a graduate student studying biology at Harvard University

Sean Wilson is a fifth-year graduate student in the Department of Molecular and Cellular Biology at Harvard University.

PSA: The first full week of October was National Mental Illness Awareness Week (MIAW).

The National Institutes of Mental Health has additional resources for those with mood disorders, including finding mental health providers in your area and affordable treatment options. If you are in crisis, you can contact the suicide prevention hotline at 1-800-273-8255 (24/7, toll-free).

Further Information:

One thought on “When Everything Hurts: The story of a grad student trying to rise above chronic pain and depression

  1. I am a Michigan chronic pain patient from a spine injury years ago from a spinal cord stimulator trial to treat a pinched nerve. The temporary wire lead placement went thru the CFS liner near the T8, blood filled the spine, and pooled around the L3 area, probably where I had a putty fusion 3 yrs prior. Underwent emergency decompressive surgery and partially paralyzed ever since. Transferred to Rehab Institute of MI, learning how to live life in a wheelchair, I started getting some movement in my right foot (toes only). 6 months of grueling work later to learn how to walk again, I came home in a wheelchair and had the whole house equipped with handicap amenities. The neuropathic pain was unbearable but I was given strong pain meds to get me thru the days and much harder nights. Night time can be pure torture for sufferers of badly damaged nerves. In another life, I was an engineer with a good company; good pay, many hobbies, classic cars, motorcycles, outgoing & sociable. I scarcely remember that life.

    The hard physical therapy work didn’t pay off as hoped and I stopped progressing after a year or so and became stuck in a half paraplegic like ailment. All body functions are similar to a paraplegic, total loss of penile & most bowel feelings (I mercifully spared you the disgusting details), one used to be good leg, one 20% functional with a mostly paralyzed left ankle and foot, but I became able to walk again. Albeit very slowly with a cane, but I could walk! You would think this is a good thing. It is not. Nerves in my lower body constantly set off fireworks that my brain thinks certain areas are in acute chronic pain. Walking, standing, sitting, almost anything I do creates chronic pain. Nights can get so bad you would have to experience this to fully understand. It’s tough day and night even with the help of a loving wife and wonderful son. Combined with a 60% pay cut from a partial pension & disability pay, burning thru a 401k, life is rarely enjoyable anymore but actually became so much worse recently.

    With true pain management and a cane, I could function enough for things like dining out, local festivals, movies, doing small tasks, etc. Not much, but I could do things even all the neuropathic pain in my lower body. I also went to a therapy gym 3 times a week. Nevertheless, I was still in bad shape and only one weekend away from home since the injury 4 years ago. I also have to miss our annual trips to visit other countries. I’m fortunate to have a caring wife and helpful teenage son, but this has been very traumatic for them as well.

    Then the opioid crisis came. The government had to clean their own opioid mess created by the big pharma companies and most states follow the lowest CDC guidelines (no opiates). Many chronic pain patients became caught in the middle and lost all quality of life, some changed to illegal drugs and some decide life was not worth living. Just google some articles and you can see for yourself how bad things are. The summer of the pain med cuts, I would truly ride a bike around my neighborhood. Getting on & off was challenging but it was such a wonderful feeling. Unfortunately, this only happened about a dozen times that summer. But what happened prior to Thanksgiving 2019 is much worse. Most nights I wish I never regained any feeling and stepped out of that wheelchair.

    I’ve tried almost everything but the pain just gets worse. I have a wife and son but cannot go on with this pain any longer, it’s exhausting, the anxiety, chest tension, headaches and wicked pain in my legs that turns to a heavy burning sensation every time I fall asleep for an hour or two. I just can’t take it anymore, my blood pressure is crazy bad and I take pills and wear a patch. But removing the BP patch, no BP pills, take a bunch of valiums and I should have another seizure and never wake again (2 seizures in the last 2 years). I have a DNR in case the next seizure turns me into a vegetable. God I am so close to completing this task. I would like to live, but cannot with this 24 hr pain anymore. The time has to come soon, each night seems to get harder and its been a long time. I cannot even remember my life prior to this pain.

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