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Complications of Uncontrolled, Persistent Pain

Persistent, unremitting pain may adversely affect the body’s endocrine, cardiovascular, immune, neurologic and musculo-skeletal systems and require aggressive treatment of the pain as well as the resulting complications.
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Hypotestosteronemia is now recognized as a common complication in persistent pain patients — both male and female. Opioid treatment potentiates testosterone deficiency.20 Since testosterone is the major androgen in the body having tissue building and healing attributes, adequate serum levels are essential. Testosterone also interacts with endogenous opioids to provide pain relief, and it is essential for libido in both sexes.21 Fortunately, testosterone replacement is now a simple clinical procedure thanks to a number of available agents.

Immune suppression is present in the persistent pain patient.22,23 It is manifested clinically by poor resistance against infections and slow healing of wounds or injuries. Hormonal abnormalities are most likely responsible. At this time, little is known about pain’s affects on such hormones as glucagon, thyroid, insulin, growth hormone, estrogen, progesterone, and endorphins, but derangement of any of these — in addition to cortisol, pregnenolone, and testosterone — may adversely affect the immune system. Serum testing of persistent pain patients typically shows a variety of serum immune abnormalities. Opportunistic infection is another hallmark of a suppressed immune system. Persistent pain patients, particularly those with an autoimmune disease such as fibromyalgia or systemic lupus erythematosis, may develop infections such as chlamydia, cytomegalus, and herpes. It may be that the same nervous tissue the produces pain is so injured that it becomes fertile ground for viruses that like to invade nerves.

Neuropsychiatric Complications

Persistent pain generates excess electrical activity in peripheral nerves, spinal cord, and brain. This “hot wire” effect appears to cause degeneration of nerve tissue — particularly in the dorsal horn of the spinal column.24 A recent controlled study shows that low back pain patients may develop cerebral atrophy.25 It follows that dementia and other organic brain syndromes may result.

The problems of insomnia, depression, suicide, attention deficit, memory loss, and cognitive deficiencies are extremely common in persistent pain patients.4-6,26 The precise biologic mechanisms by which persistent pain causes these complications is not totally clear, but they likely occur due to multiple adverse biologic affects including neuroanatomical degeneration, hormonal abnormalities, and neurochemical depletions at synaptic junctions.

Clinical Management of Complications

Understanding of the diagnosis and management of persistent pain’s profound complications are at an early stage. Nevertheless, there are some basics that can be incorporated into management of the persistent pain patient. Functional assessment of “deconditioning” and “overload-overuse” deficiencies should be done at the initial physical examination. An exercise and prosthesis program to minimize the degeneration of ancillary tissues is critical if deficiencies are found. Routine blood pressure and pulse monitoring by the patient is helpful to gauge pain control. At-home blood pressure-pulse monitoring to help assess pain control can be very revealing. Blood pressure should be below 140/90 mmHg and resting pulse below 84 per minute. Mental evaluation to detect depression, attention deficit, insomnia, memory loss, and cognitive deficits is advised. Standard treatments for these complications are essential to provide an acceptable quality of life for pain patients. Screening patients for evidence of hormonal and lipid abnormalities is simple. Glucocorticoid and sex hormone function can be easily screened by a single, early morning fasting blood specimen to determine serum concentrations of cortisol, pregnenolone, and testosterone. Abnormal concentrations of cortisol or pregnenolone may indicate poor pain control. Low concentrations of any of these three hormones may require replacement when aggressive pain treatment isn’t successful in normalizing serum concentrations.17 As part of routine clinical monitoring, the practitioner should develop procedures and protocols to periodically assess the complications of uncontrolled pain. Treatment modalities should be aggressively pursued if previous complications worsen or new ones appear.

Signs and Symptoms of Glucocorticoid Abnormalities
Glucocorticoid Excess
Weight Gain Menstrual Irregularity Depression
Lethargy Cognitive Dysfunction Memory Loss
Osteoporosis Paranoia/Psychosis Back Ache
Fractures Muscle Weakness Hypertension
Bruising Striae Loss Scalp Hair
Ankle Edema Renal Calculi  
Diabetes/Decreased Glucose Tolerance
Glucocorticoid Deficiency
Weakness Fatigue/Tiredness Salt Craving
Weight Loss Constipation/Diarrhea Tachycardia
Hyperpigmentation Nausea/Vomiting/Anorexia Anemia
Postural Dizziness Vitiligo Muscle/Joint Pains
Auricular Calcification Hypokalemia Hyponatremia
Hypotension (<110mm Hg Systolic)

Table 2. Signs and symptoms of glucocorticoid abnormalities19


Severe incurable, persistent pain will invariably produce a number of complications like any other disease. While complications have been categorized here as deconditioning, hormonal, and neuropsychiatric, future research and clinical experience may provide a more useful and detailed classification. Even more important is that our knowledge and understanding of pain complications is at an early phase, and it is critical that we move this early phase into one of better understanding for practical, clinical application.

Figure 1. Biological stress response from persistent pain.

It is certainly proper to refer to severe persistent pain as a disease or syndrome.1 The pain practitioner will need to assess the pain patient for complications and develop strategies to simultaneously control persistent pain and its debilitating, often lethal, complications.5

Last updated on: January 28, 2012