How Are Chronic Pain and Depression Related?

Post by Laura Maile

What is chronic pain?

Pain is a necessary part of life. It helps us learn what is dangerous and how to avoid things that will cause injury to our bodies. In many instances, however, the acute pain that alarms us to a potential threat to our physical safety can outlast both the source of the harm and our physical recovery from the initial injury. When this happens and the pain lasts more than three months, it is called “chronic.” Chronic pain, which is endured by 100 million people in the US alone, is a burden that causes daily suffering, reduces quality of life, often leads to loss of work, and negatively impacts mental health.  

Normally, when an injury or environmental stimulus causes us pain, something has caused physical damage, like burning a finger on a hot stove or surgery to repair a broken arm. In these situations, nociceptors (a type of neuron), receive signals of that damage in the part of the body that is hurt and relay those messages to the spinal cord and then the brain, where those signals are often interpreted as pain. In many instances of chronic pain, there is no apparent ongoing damage in the parts of the body where pain is felt. Pain, therefore, exists in the brain, not in the body. It is now understood that chronic pain can be a symptom of disease, such as cancer-related pain and chronic headache, or it can be a disease in its own right, which is seen in conditions like fibromyalgia.  

How are pain and mood disorders related?

Chronic pain and mood disorders like depression occur frequently in the same patients and tend to exaggerate the symptoms of one another. Studies indicate that if you have major depressive disorder (MDD), you are three times as likely to develop chronic pain. According to the World Health Organization, if you have persistent pain you are four times as likely to have a mood disorder like anxiety or depression. In addition to their frequent co-occurrence, the severity of symptoms also plays a role. In one study of older adults with chronic pain, both the number of body parts affected and the frequency and severity of pain were associated with a higher incidence of depression. In another study where patients were followed for 12 months, a change in the severity of depression symptoms strongly predicted an increase in the severity of reported pain. Chronic pain, understandably, can lead to feelings of loneliness, despair, and anxiety. Symptoms caused by pain, such as loss of sleep, can exacerbate those feelings, many of which overlap with symptoms of depression. It may therefore seem logical that individuals with chronic pain are more likely to develop mood disorders like depression. Why though, are people with depression more likely to develop chronic pain? 

Neurobiology of chronic pain and depression

Both chronic pain and depression have been studied for decades in humans and animal models. Pain researchers have uncovered a set of brain regions involved in pain processing, often called the pain matrix. These include areas of the medial prefrontal cortex (mPFC), anterior cingulate cortex, the somatosensory region of the parietal cortex, insula, amygdala, thalamus, nucleus accumbens, and areas of the midbrain including the periaqueductal gray. Importantly, these regions do not exclusively process pain but are important for various other functions including emotional regulation, motivation, memory, and cognition. Some regions of the pain matrix, like the mPFC, insula, and amygdala, are more significantly involved with the affective emotional component of pain that causes suffering, rather than other elements like location and intensity. These regions are also important in processing emotion and analyzing the contextual and emotional significance of relevant stimuli to help drive behavior.  When patients with acute pain transition to chronic pain, reorganization occurs in the brain that shifts activity patterns, often increasing the activity in the emotion regulation areas. This may help explain why chronic pain often coincides with mood disorders, which are associated with changes in some of the same brain regions. Additional changes in gray matter volume, neural activity, or connectivity occur in overlapping regions of the brain in both depression and chronic pain. For example, both animals and patients with chronic pain show a decrease in both activity and volume of the mPFC. This is similar to observations made in both depressed patients and animal models of depression. 

What’s the treatment for depression and chronic pain?

While drugs like opioids have had success in treating intense pain associated with surgery or traumatic injury, they are insufficient in the treatment of chronic pain and come with dangerous side effects like addiction that have influenced the ongoing opioid epidemic. While a few drugs can offer some help with ongoing symptoms, many chronic pain patients find little to no relief from current drug options. There is therefore an urgent need for more effective treatments for ongoing pain. Treatments for depression and chronic pain often overlap. Tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) are often prescribed, with positive effects, in the treatment of both depression and pain. Ketamine, a drug known to be effective in treating acute post-operative pain, shows promise in treating major depressive disorder, with documented improvement of symptoms in treatment-resistant patients. Though its positive effects on depression symptoms occur more quickly than traditional SSRIs, ketamine administration must be repeated often, and it comes with negative side effects, including the potential for abuse. It also shows limited efficacy in treating chronic pain. In addition to drugs, there are also alternative treatments such as psychotherapy and cognitive behavioral therapy (CBT) that offer assistance for those struggling with mood disorders and chronic pain. Though not a complete replacement for drugs or other treatments, evidence suggests CBT can improve symptoms of ongoing pain in some patients. Similarly, CBT and other forms of psychotherapy can lead to the improvement of symptoms in patients with MDD or anxiety disorders, though some reports indicate these effects may be overestimated in many publications. 

What does the future look like?

Despite the dual nature of these diseases, the neurological basis for the overlap in chronic pain and mood disorders is still unclear. Research is ongoing at both the basic and clinical levels, to better understand the neural biology of both diseases and how they may impact one another, and to develop better treatments that target both diseases. Recent research into psychedelics is quickly changing our understanding of ways major depression, post-traumatic stress disorder, and chronic pain, may be successfully treated.  Clinical trials are ongoing, but evidence suggests that psychedelics such as lysergic acid diethylamide (LSD) and psilocybin may be effective in treating both intractable mood disorders and chronic pain conditions such as migraine. These drugs also may represent future positive alternatives to drugs associated with abuse like opioids. 

Pain and mood disorders, though distinct, overlap in the brain areas affected. These debilitating disorders are a huge cost to human health and wellbeing, making the continued advancement of both basic and clinical research into the neuroscience of these diseases and novel treatment options essential.

References +

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