Here’s some more interesting reading on pain, HPA axis, and Cortisol. Also mentioned briefly is thyroid hormone related to pain.

Editor’s Memo

by Forest A. Tennant, MD, DrPH

It’s now been almost 30 years ago that I began my pain management clinic. The early patients were heavily weighted towards cancer, post-polio, and back-trauma patients. A standard practice in those days was to do a rheumatic disease blood panel, and I was intrigued at the high percentage of pain patients with one or more positive immune tests such as C-reactive protein, anti-nuclear antibody, sedimentation rate, and rheumatoid factor. I developed the theory that the patients must have some genetic, immune, or collagen disease that made them susceptible to the development of a painful condition or that prevented proper healing after trauma or surgery. It turns out my theory didn’t hold much water, but I was so curious that I began searching the literature for clues as to why pain patients had so many positive immune tests. I discovered that a reasonable number of good scientific studies on biochemical changes in pain patients had already been reported particularly by British physicians. Such changes included abnormal corticoid secretion and serum carbon dioxide levels.1 This early literature was notable in that observed biochemical changes were generally believed to be rather innocuous, diagnostic tracers or markers for the presence of pain and not a serious complication of pain. The idea of a biologic tracer or marker carried into the 90’s. The military wanted to find a marker to separate malingerers from legitimate pain patients and believed they found one when a group of pain patients were discovered to have low serum triiodothyronine levels.2 Others, including this editor, believed that one or more biologic markers might identify valid pain patients as opposed to addicts.3

As time and research marched on, it became evident that there are no innocuous tracers or markers in severe pain patients. The biochemical alterations and markers observed in severe, chronic pain patients are actually complications of pain itself. Although chronic pain may exert its dirty work by multiple biologic mechanisms, one stands out. Severe pain—both acute and chronic—activates the hypothalamus-pituitary-adrenal axis. Consequently, there is hyper-secretion of catecholamines and glucocorticoids which raise blood pressure and pulse rate. The abnormal adrenal secretions produced by severe, chronic pain likely cause some of the immune abnormalities observed in pain patients. Fundamentally, the most objective, physiologic signs of uncontrolled pain are tachycardia and hypertension. In addition to adrenal hormone release, elevated pulse rate and blood pressure are likely to also result from pain over-stimulating central adrenergic centers. The astute, in-depth practitioner can easily and certainly document adrenal abnormalities by simple serum screening of cortisol and pregnenolone. No need for a 24-hour urine collection for catecholamine assay or an ACTH challenge test.

Why is documentation of over-stimulation of the hypothalamus-pituitary-adrenal axis so critical? Two reasons. One is simply welfare of the patient. Asking the patient to rate their pain 1 to 10 is fine, but this is hardly an objective way to categorize pain into the usual clinical categories of mild, moderate, and severe. Simply, all physicians from the wide-eyed intern to the gray-haired sage need to evaluate every pain patient with a pulse and blood pressure reading. Obviously, the pain patient with a pulse rate of lets say, 100 a minute, needs a far more aggressive treatment approach than one with a pulse rate of 76.

The second reason to put some objectivity to pain categorization is a practical one: reimbursement. Costs of the most potent pain treatments — be it Schedule II opioids, intrathecal administration, or a implanted electrical stimulator — can only be considered catastrophic. We need to give the bill-payors—sometimes known as insurance companies, HMO’s, health plans, and skin flints—additional, objective categorization rather than “10 on the pain scale.” Try it. They listen on the other end of the phone when you mention constant pain, debilitation, pulse rates over 90, and a high cortisol. This is doctor talk. I personally don’t have much trouble with reimbursement these days: I just indicate that I’ve documented tachycardia and a low pregnenolone serum level in the patient.

Bottom line. Pain is now the 5th vital sign, but don’t ignore a couple of the others.

—Forest A. Tennant, MD, DrPH
Editor in Chief

References
1. Glynn CJ and Lloyd JW. Biochemical changes associated with intractable pain. Br Med J. 1978. 1:280-281.
2. Dons RF and Shaki KMM. Changes in triiodothyronine mark severe pain syndrome: a case report. Military Med. 1994. 159:465-466.
3. Tennant F and Herman L. Using biologic markers to identify legitimate chronic pain. Amer Clin Lab. June 2002.

— September 2006