Brain Atrophy with Chronic Pain: A Call for Enhanced Treatment

Recent studies clearly show that chronic pain unto itself causes brain atrophy and altered neurochemistry and sensory function of the central nervous system.
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As unpleasant as it may be, the evidence is in: chronic pain may produce a loss or atrophy of brain tissue.1-8 All practicing physicians and their surrogates and allies must immediately begin understanding the ramifications of this finding. All parties must be educated about this fact and aggressively attempt to prevent brain atrophy in chronic pain patients. While our knowledge about this dire complication—and what tools we should employ to prevent and treat it—are admittedly meager, we have to begin a new chapter in practical pain management.

The Evidence

In 2004, Apkarian and colleagues at Northwestern University published their initial findings on patients with chronic back pain.1 By use of brain scans they determined that chronic pain caused brain shrinkage by as much as 11%—equivalent to the amount of gray matter that is lost in 10-20 years of normal aging. The decrease in volume in the prefrontal cortex and the thalamus of the brain was related to the duration of time spent in pain. Every year of pain appeared to decrease gray matter by 1.3 cubic centimeters. The good news about this study is that the shrinkage was accompanied by only minimal neuronal loss suggesting that proper treatment might reverse this portion of the decreased brain matter.

Since this seminal report, a number of investigators—from a variety of institutions, using a variety of techniques—have documented loss of brain tissue in chronic pain patients, including those with chronic headaches, fibromyalgia, back pain, and irritable bowel syndrome.2-6 Most of the major studies involving chronic pain and brain tissue loss are referenced here for readers who wish to explore these findings in greater detail.2-8

In any discussion or study of chronic pain complications, the question about drugs—particularly opioids, as a causative factor—is naturally asked. All the studies noted above had at least some subjects who did not take opioids. To determine whether brain structural changes occur independent of opioids, Buckalew and colleagues at the Universities of Pittsburgh and West Virginia carefully studied a group of older adults with chronic pain who did not take opioids and who had none of these confounding conditions: hypertension, diabetes, major depression disorder, post-traumatic stress disorder, or a previous stroke.8 They found essentially the same altered and reduced brain matter as all of the other studies.1-7 It is also cogent to point out that long term opioid therapy has not been found to produce significant decreases in neuro-cognitive abilities.9,10 In fact, adequate pain relief may improve them.9

Not only have scans and magnetic imagery documented the loss of gray matter, a number of other studies complement these findings in that the brains of chronic pain patients demonstrate altered neurochemistry and central nervous system processing of input signals such as odors, taste, heat, emotions, and touch.11-16 Studies show that chronic pain patients do not process external stimuli in a normal fashion.11 Patients with chronic back pain have altered dopamine and opioid availability in the forebrain.17,18 Fibromyalgia patients appear to have a reduction in the receptor availability of dopamine and opioid mu-receptors in parts of the forebrain.19,20 In summary, it appears that brain neurochemicals important for pain modulation are not responding as they do in healthy individuals.11-20

Table 1. Risks of Chronic Pain
  • Brain atrophy
  • Altered brain neurochemistry
  • Altered brain sensory processing
  • Hypertension
  • Tachycardia
  • Immune suppression
  • Elevated adrenal corticoids
  • Adrenal exhaustion
  • Depression
  • Physical immobility
  • Deranged activities of daily living
  • Insomnia
  • Anorexia and malnutrition
  • • Suicide

Not only have scans and magnetic imagery documented the loss of gray matter, a number of other studies complement these findings in that the brains of chronic pain patients demonstrate altered neurochemistry and central nervous system processing of input signals such as odors, taste, heat, emotions, and touch.11-16 Studies show that chronic pain patients do not process external stimuli in a normal fashion.11 Patients with chronic back pain have altered dopamine and opioid availability in the forebrain.17,18 Fibromyalgia patients appear to have a reduction in the receptor availability of dopamine and opioid mu-receptors in parts of the forebrain.19,20 In summary, it appears that brain neurochemicals important for pain modulation are not responding as they do in healthy individuals.11-20

Implications of These Findings

The findings in chronic pain patients of brain tissue loss and altered central nervous system physiology and neurochemistry is a profound discovery that should be known to all physicians. Implications of this discovery are clear. Recently, in an educational document published by the American Academy of Pain Management, Dr. Catherine Bushnell of McGill University in Montreal, who is a principal investigator in many of the studies referenced here stated, “The data suggest that patients should receive treatment as early and as aggressively as possible. The old adage “no pain, no gain” appears to be diametrically opposed to current findings about the impact of pain.” She, and possibly some previous fence-sitters, now want to call chronic pain a disease unto itself.

It is now clear that the risk-benefit ratio of aggressive treatment versus moderate treatment—which leaves the patient with some degree of constant pain—needs to be reevaluated. Brain atrophy, along with altered brain physiology and neurochemistry, now joins the risk profile of undertreated chronic pain. To date, this risk profile has consisted of hypertension, tachycardia, altered adrenal hormone levels, suppression of the immune system, depression, and interference with physical function and activities of daily life (see Table 1). It is now abundantly clear that chronic pain, particularly the severe intractable form, is a disease unto itself whose risks, per se, appear to far outweigh those of essentially all applicable medical treatments—including high dose opioid therapy.9,10

Table 2. Four Clinical Cases Who Mentally Deteriorated

1. A 25-year-old female was referred with severe chronic pain due to fibromyalgia. She claimed undertreatment for at least three years which interfered with her promising career. Morning serum cortisol levels were over 30ug/dl and she had a resting heart rate over 110 beats per minute. Despite aggressive opioid and other treatment, within 10 years she became so mentally incapacitated that she could not work, was home-bound, and had to be cared for by family.

First published on: March 1, 2009