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5 Articles in Volume 4, Issue #1
Complications of Uncontrolled, Persistent Pain
Improving Postoperative Pain Outcomes
Peripheral Nerve Catheters for Acute Pain Control
The ABC's of Pain Clinic Referrals
Treatment-resistant Migraines

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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To the unfortunate patient who is afflicted and the practitioner who treats it, incurable, persistent pain is truly its own disease regardless of its underlying cause.1-3 Persistent pain, which is also often characterized as chronic or intractable, has all the ramifications of a disease in that it may have pre-clinical and overt phases.4-6 It may be intermittent or constant, as well as, mild, moderate, or severe. The most unappreciated clinical feature of persistent pain, however, is the plethora of complications that may result — particularly if the pain is constant and unremitting.

Many recent and emerging studies clearly document that persistent pain exerts profound impacts on the body’s endocrine, cardiovascular, immune, neurologic and musculo-skeletal systems.7 Presented here is a review and classification of some of persistent pain’s complications to give the practitioner a basic understanding that persistent pain may produce a symptom complex or syndrome that must be recognized at the clinical level.1 Even though our understanding of the occurrence and mechanisms of the persistent pain syndrome are still quite limited, it is clear that the diagnosis and treatment of persistent pain’s complications must be simultaneous with pain treatment.

Deconditioning Complications

Any area of the anatomic body that experiences severe persistent pain will soon “decondition.” This area will cease normal, symmetric, coordinated movement, and the patient will simply self-splint, immobilize, and decondition the area. This leads to a number of complications including muscle atrophy, neuropathies, and in late stages, contractures. Muscle, nerve, and joint weakness, and deterioration result. It is not uncommon to see the patient with severe, uncontrolled pain progressively deteriorate due to muscle atrophy and contractures and go from cane to walker to wheelchair.

An unappreciated complication of deconditioning and immobility is obesity. Excess weight may further overload a painful, deconditioned anatomical site.

A single painful location on the body soon begets some others. Much of this is the “overload and overuse syndrome.” To make up for a weak, painful area, joints, nerves, and muscles elsewhere in the anatomy will attempt to compensate and work overtime. Unfortunately, chronic overuse and overload may lead to tissue degeneration at secondary pain sites causing arthropathies, myopathies and neuropathies. Pain patients sometimes develop a more painful secondary site than the primary site. The astute practitioner can often observe physical evidence of overuse, overload, and self-splinting such as the presence of hypertrophy of paraspinal or neck muscles, unilateral furrows of the brow in the persistent headache patient, and calluses on the foot in the patient with back, hip, or leg pains.

Hormonal Complications

Based on emerging research data, it appears that uncontrolled persistent pain may affect about every endocrine system in the body.8-11 It has long been observed that acute pain is often accompanied by hypertension and tachycardia, and it is now clear that persistent pain may actually trigger indolent hypertension and tachycardia.12 Excess catecholamine and glucocorticoid production is certainly contributory to these complications, but there may also be a stimulatory neurologic etiology caused by uncontrolled pain. Insulin and lipid metabolism may be altered, and recent studies with spinal cord injuries and systemic lupus erythematosis suggest that persistent pain may accelerate the atherogenic process.13,14 Cardiovascular death is a common occurrence among persistent pain patients likely due to a multitude of factors.

The impact of persistent pain on the hypothalmic-pituitary-adrenal-axis is profound and paramount to understanding the complications of persistent pain.7,15-18 Severe pain is a potent stressor — perhaps the most potent — that stimulates this system.7 Persistent pain initially produces excess secretion and high serum concentrations of catecholamines and glucocorticoids as the body attempts to control pain and prevent damage.12,18 If severe, persistent pain isn’t controlled, adrenal exhaustion and decreased serum levels of glucocorticoids, including cortisol and pregnenolone, may result.17,18 Even though the adverse affects of persistent pain on the pituitary thyroid, pancreas, pineal, testes, and ovary are less clear, all are likely impacted.8 Although the complex assault on the endocrine systems of the body by persistent pain begs for more research, it is clear that the severe, persistent pain patient may experience all the ramifications of excess and/or deficiency of glucocorticoids.19 Excess and deficient serum levels of glucocorticoids, often known as Cushing and Addison syndromes, respectively, manifest a diverse range of signs and symptoms in patients having severe, persistent pain. Table 1 presents a compilation of the signs and symptoms of these conditions. Note that patients with severe persistent pain may demonstrate either glucocorticoid excess or deficiency. Apparently, persistent pain patients can go from excess to deficiency states over time and demonstrate both states.10,11 Abnormal glucocorticoid states may have debilitating consequences including mental deficiencies, muscle weakness, edema, osteoporosis, diabetes, and stone formulation among others. Also, likely related to glucocorticoid abnormalities is the common observation of severe tooth erosion and decay. Furthermore, abnormal glucocorticoid levels likely interfere with pain control.15,16

Classification of Major Complications of Persistent Pain


  1. “Overuse” of ancillary musculoskeletal tissue with degeneration
  2. Decreased mobility
  3. Obesity
  4. Muscle atrophy
  5. Contractures
  6. Neuropathies


  1. Excess catecholamine production with hypertension and tachycardia
  2. Glucocorticoid excess or deficiency
  3. Hypotestosteronemia
  4. Insulin - Lipid abnormalities
  5. Immune suppression


  1. Nerve - Spinal cord degeneration
  2. Cerebral atrophy
  3. Depression/suicide
  4. Insomnia
  5. Attention deficit
  6. Memory loss
  7. Cognitive decline

Table 1. Classification of major complications of persistent pain

Last updated on: January 28, 2012
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