The Relationship Between Chronic Insomnia, Pain, and Depression

Question:

"I have noticed that my patients suffering from chronic insomnia, pain, and depression all have similar symptoms. Is this more than a coincidence?"

Vladimir Maletic, MD:

Let’s start our answer by considering a typical clinical scenario. Ms. X is a 43-year-old female complaining of feeling tired, sleepy, and “foggy.” Her body is sore and achy “all over.” She has little enthusiasm, limited ability to focus and complete tasks, and lacks appetite. Does Ms. X suffer from chronic pain, depression, fibromyalgia? Is she coming down with the flu? Or is Ms. X really a Dr. X who has just had a horrendous night on call? We really cannot be too sure, can we?

Sleep has an important role in immune modulation. It appears that innate immunity has its peak during the night, while acquired immunity tends to be allocated to wake hours. ¹ We are not quite sure what is the adaptive value of this “division.” Innate immunity taxes our metabolic capacities to convert our body into an inhospitable environment for the invading microbes. ² It is mediated by peripheral mononuclear cells, inflammatory cytokines, chemokines, adhesion molecules, and prostaglandins. During the night there are fewer competing metabolically-intense processes, therefore it may be an optimal time for innate immunity.

What happens if our nighttime sleep is disturbed? Individuals who do not sleep well are known to have a greater risk of cancer and less response to vaccines. It appears that lack of nighttime sleep shifts peak levels of inflammatory cytokines (such as IL-6) to morning hours. In the same context, anti-inflammatory cytokines (IL-10) have lower daytime levels. ¹ In other words: our mornings become more inflammation-laden!

Neuropsychiatric symptoms commonly associated with elevated inflammation include: somnolence, fatigue, impaired concentration, irritability, anxiety, depressed mood, diminished appetite and sex drive, and lower pain threshold. ³ Sounds familiar? It should not come as a surprise then that insomnia is a predictor of widespread pain, depression, and anxiety. ^3,4 Insomnia is also one of the most frequent residual symptoms of depression and a prognosticator of relapse, even in treatment responders. ⁵ If individuals afflicted with fibromyalgia do not sleep well, they are likely to have pain in more sites during the tender point exam the next day; stress will have a similar effect. ⁶ Fibromyalgia patients who also suffer from anxiety and depression show greater increase of inflammatory indicators (IL-8) than healthy controls or individuals who suffer from fibromyalgia alone. ⁷ A recent study found that sleep disturbance enhances the negative affect experienced by chronic pain sufferers. ⁸

The relationship between insomnia, mood, and pain disorders is not casual, it is causal! These conditions are organically intertwined, sharing pathophysiological mechanisms such as neuroendocrine disturbance, altered autonomic regulation, and elevated inflammatory response. ³ Our patients would most benefit if we viewed insomnia as a bona fide pathological entity, not just as a symptom of another neuropsychiatric or general medical disorder. Screening psychiatric and pain patients for insomnia, especially women older than 45, followed by prompt and effective therapeutic intervention may significantly improve the quality of care.

1. Lange T, Dimitrov S, Born J. Effects of sleep and circadian rhythm on the human immune system. Ann N Y Acad Sci. 2010;1193(1):48-59.
2. Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry. 2009;65(9):732-741.
3. Maletic V, Raison CL. Neurobiology of depression, fibromyalgia and neuropathic pain. Front Biosci. 2009;14:5291-5338.
4. Gupta A, Silman AJ, Ray D, et al. The role of psychosocial factors in predicting the onset of chronic widespread pain: results from a prospective population-based study. Rheumatology. 2007;46(4):666-671.
5. Cho HJ, Lavretsky H, Olmstead R, et al. Sleep disturbance and depression recurrence in community-dwelling older adults: a prospective study. Am J Psychiatry. 2008;165(12):1543-1550.
6. Kamaleri Y, Natvig B, Ihlebaek CM, et al. Number of pain sites is associated with demographic, lifestyle, and health-related factors in the general population. Eur J Pain. 2008;12(6):742-748.
7. Bazzichi L, Rossi A, Massimetti G, et al. Cytokine patterns in fibromyalgia and their correlation with clinical manifestations. Clin Exp Rheumatol. 2007;25(2):225-230.
8. Hamilton NA, Catley D, Karlson C. Sleep and the affective response to stress and pain. Health Psychol. 2007;26(3):288-295.