Chronic Pain and Mood Disorders-Identifying and Understanding Shared Neurophysiological Mechanisms

Q: You recently gave a presentation, “Understanding the Mind-Body Relationship,” at the U.S. Psychiatric and Mental Health Congress in Las Vegas. What has recent research told us about the relationship between chronic pain and mood disorders?

A: Mood disorders and chronic pain are related on multiple levels. The genes that regulate the synthesis of serotonin transporter, opioid receptors, and inflammatory mediators seem to be compromised in patients with major depressive disorder (MDD) as well as in patients with chronic pain. Other similar factors may predispose individuals to chronic pain and depression. For example, major stressful events may be related MDD and chronic painful conditions, such as fibromyalgia.

Neither MDD nor chronic pain conditions are homogenous entities. In either scenario, we’re dealing with umbrella diagnoses that subsume a number of biologically diverse conditions. Ample evidence suggests that the presence of MDD or another mood disorder tends to augment the experience of pain in patients with chronic pain.

The mechanisms of these diseases overlap significantly. The circuitry in the brain involved with regulation of mood and stress response overlaps with the pain matrix-areas involved with processing pain. The areas involved in both pathological states include the amygdala, hippocampus, thalamus, anterior cingulate, prefrontal cortical areas, and insular cortex.

Finally, one can observe changes in endocrine and hypothalamic-pituitary-adrenal function in patients with either chronic pain or mood disorders. Both conditions are also associated with alteration of neuroimmune function and elevated inflammatory response as well as autonomic dysregulation along with increased sympathetic tone. All of these underlying neurobiological similarities probably produce similar clinical manifestations. Patients with chronic pain, much like those with depression, may have cognitive impairment, sleep disturbances, diminished ability to enjoy life, difficulty with concentration, and fatigue.

Q: Patients with fibromyalgia also have a high incidence of comorbid MDD? . How are these specific conditions similar?

A: An interesting similarity between MDD and fibromyalgia has to do with kindling phenomenon, which proposes that in patients with mood disorders, frequent mood episodes increase the likelihood of symptom recurrence. There is possibly even greater morbidity and symptom severity associated with future recurrences. We have seen a very similar phenomenon in neuropathic pain and fibromyalgia. The duration of pain seems to augment the underlying pathology and increase the patient’s experience of pain and suffering.

Some similar mechanisms may also be involved at the synaptic level. Excessive glutaminergic transmission is found in both MDD and fibromyalgia. There is an impairment in the collaboration between nerve cells and glial cells, including astroglia, microglia, and oligodendroglia. This profound disturbance in synaptic signaling can be consolidated by increases in neurotrophic factors in chronic pain conditions. Thus nerve fibers “learn” pain. So indeed, there are synaptic, cellular, and even subcellular changes that would suggest that there is some similarity between fibromyalgia or neuropathic pain and MDD.

Interestingly, all of these conditions affect the integrity of the hippocampus. This is a critical brain area because it is involved with regulation of stress response as well as emotional modulation and cognitive processes, such as declarative memory. The negative effect of the hippocampal dysfunction is intriguing because it could be associated with neuroendocrine, autonomic, and eventual neuroimmune alterations. With the disturbance in hippocampal function, one may also appreciate telltale cognitive signs. Patients with fibromyalgia or MDD often have problems remembering names, expressing themselves accurately, and recalling where they put things.

Q: Based on the results of your research, how do you approach patients presenting with mood disorders or chronic pain?

A: It is not always easy to translate advancements in neurobiological understanding of MDD and chronic pain disorders into clinical practice, but there are some important lessons. Given that these conditions may have a shared underpinning, it would behoove us to evaluate patients with MDD comprehensively to determine whether some of their symptoms may also be caused by chronic pain. It may be helpful to ask more pointed questions about pain. Lately, I have been surprised to find out that some of my patients with mood disorders, especially those who have not responded well to treatment, actually had a chronic pain condition. Very often it was fibromyalgia. Comorbidity may also direct our choice of treatment. Maybe we can find medicines that will benefit both mood and pain.

Patients with fibromyalgia are likely to have a comorbid mood disorder, which suggests that these patients would benefit from an evaluation focusing on mood disorders. In addition, these conditions share pathophysiological mechanisms that tend to influence a patient’s risk for metabolic diseases, especially type 2 diabetes as well as cardiovascular and cerebrovascular diseases. So the patient’s general medical status is an important consideration.