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Types of Neuropathic Pain
By Mark J. Lema, M.D., Ph.D.

The definition of neuropathic pain is fairly straightforward. As the name indicates, it is a ‘disease or disorder’ involving the nerve itself as the source of the pain. Neuropathic pain, however, is part of the larger syndrome of ‘neuropathy’ which is a disorder/dysfunction of peripheral nerves. Peripheral neuropathies include motor, sensory and autonomic fiber derangements that feed into the central nervous system. Central nervous system disorders occur as a result of injury, stroke, disease or congenital conditions involving the brain and/or spinal cord.

Over 30% of all neuropathies are a result of diabetes in the U.S.¹ While all conditions classified as neuropathies do not always result in pain, they can be very debilitating in other ways such as muscle weakness/paralysis, sensory numbness/paresthesia, and gastric dysfunction.

Neuropathic pain classification is a taxonomic attempt by researchers and clinicians to sort out the myriad of disorders in order to conveniently study certain ‘syndromes’ with the idea of finding a treatment. Most neuropathic conditions are not isolated to pure pain fibers and can co-exist with inflammatory, visceral and/or nociceptive pain (or pain resulting from the stimulation of free nerve endings by a chemical, thermal, or mechanical event), as well as neuropathic dysfunction like autonomic nervous system involvement in diabetes. Nonetheless, broad categories to determine the cause of these insults are convenient ways to understand the pathophysiology in clinical practice.

Types of Neuropathic Pain:
The major categories of neuropathic pain include: ² ³

Toxic—The most common toxic condition causing neuropathic pain is a result of chemo-radiation in the treatment of cancer. Isoniazid and thallium are also known to cause neuropathic pain conditions.

Exposure to chemicals like lead and arsenic also result in nerve damage. Toxic exposure generally results in abnormalities in genetic/protein processing.

Metabolic—Diabetes is clearly the major cause of neuropathic pain caused by metabolic dysfunction. Nutritional deficiencies like Beriberi (vitamin B1) also produce neuropathic pain. In the case of diabetes, glycosylation end products inhibit axonal transport and Na+/K+ ATPase producing axonal degeneration.

Alcohol induced neuropathy is often a result of thiamine (B1) deficiency although it can produce its own small fiber pain pathology as opposed to a thiamine-deficient axonal sensorimotor burning neuropathy.

Trauma—Trauma can result in phantom limb syndromes and/or complex regional pain syndromes (CRPS). Phantom limb pain is thought to be a result of abrupt loss of sensory input from the peripheral limb to the brain and discharges from the nerve endings at the sight of the amputation that continue to send pain signals to the brain, making the brain think the limb is still there. There is no known mechanism that causes CRPS but many hypotheses have been suggested, including dysfunctional processing throughout the entire nervous system involving peripheral, central and autonomic neurons.

Compressive—Both nerve entrapment and excessive external pressure on nerve axons can cause ischemic or distortional (stretching) changes. Prolonged injury results in Wallerian degeneration of the axon with resultant muscle atrophy. Carpal tunnel syndrome and compartment syndromes are common entrapment injuries.

Autoimmune—This class of neuropathic pain can be quite diverse. They may have autoimmune antibodies involved in their pathophysiology and are usually amenable to immune therapy. Some examples of autoimmune neuropathic pain include chronic inflammatory demyelinating polyneuropathy (CIDP) and vasculitic neuropathy.

Infectious—Viral conditions are known to result in long-standing neuropathic pain. The classical condition is post-herpetic neuralgia caused by reactivation of the Varicella Zoster Virus. Lyme Disease (spirochetes), Chagas’ Disease (trypanosomes), leprosy (mycobacterium), HIV, and Guillain-Barré Syndrome (post-infectious) can all cause neuropathic pain.

Congenital/Hereditary—Fabry’s  Disease and Charcot-Marie-Tooth Disease (burning pain in extremities) are good examples of peripheral neuropathic pain associated with congenital abnormalities. Other hereditary conditions like amyloidosis also produce painful conditions.

Neuropathy and neuropathic pain are manifestations of a hundred different diseases that have deleterious effects on normal neural functioning. These conditions are treated by scores of medical specialists often focusing on one or a few aspects of the causative process, like cancer or diabetes. Pain scientists and clinicians must eventually deal with the common presentations of these anatomically and physiologically distinct entities once they reach their final common pathways—permanent neural damage. Just like heart disease, once the cellular damage occurs, reversing the disease state becomes impossible.

At the stage of neuropathic pain diagnosis, palliative treatment is often the only option, and effective therapies are rare. Early understanding of pathophysiologic mechanisms of disease, and prevention of irrevocable painful neural remodeling needs to become the goal of “therapy.” Interdisciplinary cooperation and institution of ‘pre-emptive’ pain therapies could prevent many from the needless suffering of neuropathic pain.

1. The Neuropathy Association Website. (Also see, Thomas H. Brannagan, III, M.D., Treatment of Painful Peripheral Neuropathies.)

2. Loeser, J. D. (Ed), Bonica’s Management of Pain, 3rd Edition, Lippincott, Williams & Wilkins, Philadelphia, 2001.

3. Warfield, C. A. and Bajwa, Z. H. (Eds), Principle & Practice of Pain Medicine, 2nd Edition, McGraw Hill, New York, 2004.

Mark J. Lema, M.D., Ph.D. is professor of Anesthesiology and Oncology, chairman of the Department of Anesthesiology, Critical Care, Perioperative and Pain Medicine, and medical director of Surgical Services at Roswell Park Cancer Institute. He is also professor and chair of the Department of Anesthesiology at the University at Buffalo State University of New York School of Medicine and Biomedical Sciences. Dr. Lema is a past president of the American Society of Anesthesiologists.


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