Neuropathy, neuralgia, neuritis and neuropathic pain 

In order to understand the mergence of the concept neuropathic pain we conducted a pubmed search with key words 'pain' and 'neuropathic' (.....en neuropathy??)  during subsequent time periods.

In a review of 2004 no clear clue was given when the concept of neuropathic pain arised.^[1] A term still in use is 'neuralgia;, and defined as “pain arising in the distribution of a nerve or nerves” The term neuritis is an old term describing an inflammation of the nervous system. In a book from Lewandowsky from 1912, the definition of neuralgia is mentioned.^[2] Although in small publications the word neuropathy was already mentioned in the thirties, in a German book written by Ewald of Neurology and Psychiatry, the word neuropathy was not yet mentioned in 1944.^[3] In a Dutch book of neurology, written by Schade and published in 1970, the definition of polyneuropathy was given, although directly mentioned that the term polyneuropathy was not yet common. Polyneuropathy was defined as usually a subacute onset of a disease affecting the peripheral nerves, characterized by long duration of the disease. Because usually there is not a clear underlying infection or -itis, the word polyneuropathy is now used.^[4]

History of the word neuropathy

In 1837 Gully wrote a book on Neuropathy with the title: An exposition of the Symptoms, Essential Nature, and treatment of Neuropathy or nervousness. In a review on this book in the Edinburgh Medical and Surgical Journal published in 1839, clear definitions were mentioned on the word neuropathy.^[5] He states that a minor degree of neuropathy is also called nervousness and a major degree of neuropathy is formely called hypochondriasis. He assumes that this disease has also a neurophysiological substrate: "the ganglionic matter distributed about the epigastium is the only permanently diseased point; while in the more intense degree, disorder of the brain is added to that of the ganglionic matter alluded to, and partially assists in the maintenance of the symptoms." The author also attributes the prevalence of this disease to a high degree of civilization:"neuropathy in any of its degrees is a disease altogether unknown among barbarous nations."

In 1848 the disease histeria was also seen as a form of neuropathy.^[6] Professor Forget of Strasbourg published a paper in Gazette Médicinale on the treatment on hysteria, which formed the last of a series on the neuroses. In this paper he also gave the definition of neuropathy: "A disorder of the nervous system". Hysteria is a true, special disease, consisting essentially in a neuropathy, (a disorder of the nervous system), the nature of which is unknown.

In 1886 neuropathy was thought to be heriditary and had still another meaning than today, which is shown in the Lancet as notes and commentaries: The tragic end of the King of Bavaria has given a fresh start to observations on the "law of hereditariness." Dr. P. Marechal, in an interesting paper, reminds us that the Royal House of Spain exemplifies a transmitted neuropathy lasting 250 years. John II. was imbecile; Isabella of Portugal mad; Ferdinand the Catholic melancholic; John, surnamed "the Mad," a victim of hallucinations; Mary Tudor hysterical; Charles V. epileptic and superstitious; Philip II., his son, a homicidal mystic; Philip III. first imbecile and then mad; Philip IV. imbecile; and his two sons, Prosper subject to convulsive fits and Charles VI. imbecile, melancholic, and finally mad. With this last, who died without issue in 1700, the family became extinct.^[7]

The first time the word "neuropathy" with pain was mentioned in an article indexed in Pubmed was in 1924 due to lead poisening.^[8] Later in 1948 Brigden described the changing thoughts on neuropathy and malnutrition.^[9] In 1958 Dyck already presented a casereport of sensory neuropathy in which he described a patient with pain, pins and needles and numbness due to carcinoma of the lung.^[10]

In 1976 for the first time painfulness in peripheral neuropathy was associated with the rate and kind of nerve fiber degnereration, described in the hallmark paper of Dyck and colleguages: Pain in peripheral neuropathy related to rate and kind of fiber degeneration. Neurology^[11] They examined 72 patients with disease of peripheral neurons. The study assessed the association of painfullness of the foot with the rate and kind of nerve fiber degeneration and with the ratio of remaining large to small fibers of the sural nerve. Painfullness was graded only when it was considered to be characteristic and distinctive of neuropathic involvement. Superficial burning, stinging, and prickling, often associated with a deep phasic aching and with momentary jabs of sharp pain were the most common discriptions of the pain. A biopsy was obtained, and the amplitude potential of the nerve was measured in vitro.
The patients scored their pain on a 4 point scale. The results of the study were that 76% patients with acute fiber degeneration had pain, compared with only 15% with other types of fiber degeneration. The second observation was that there was no difference in the amplitude potentials of Aalfa and C fibers between the two groups.

Two years later Chandler et al wrote about diabetic neuropathic cachexia and refered to this entity as an unusual syndrome within the broad group of diabetic neuropathies is characterized by extreme loss of body mass and severe neuropathic pain. ^[12]

Definition in 1994 (IASP): Peripheral neuropathic pain (PNP) is defined as pain initiated or caused by a primary lesion or dysfunction in the peripheral nervous system (Merskey and Bogduk, 1994).  

This definition includes neuralgia and painful polyneuropathy. Neuralgia is pain in the distribution of a nerve or nerves. Painful polyneuropathies are usually symmetric and distal, affecting the feet and sometimes the hands. These conditions may present with or without paresthesia, hypoesthesia, hyperalgesia and allodynia. 

In 1997 S. Kingerya wrote 'A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes' ^[13]

Recent reviews of neuropathic pain treatments referenced a total of 40 articles describing controlled trials (Fields, H.L., Peripheral neuropathic pain: an approach to management. In: P.D. Wall and R. Melzack (Eds.), Textbook of Pain, Churchill Livingstone, Edinburgh, 1994, pp. 919–995.Fields, 1994; Calissi and Jaber, 1995; Galer, 1995a) and recent CRPS reviews cited a total of 17 controlled studies (Brody and Andary, 1993; Backonja, 1994; Subbarao and Blair, 1995; Haddox and Alstine, 1996). A combined manual and computer search of the literature found an additional 15 controlled studies, for a total of 72 articles published from 1969 to 1996.

In 1990 Portenoy et al defined neuropathic pain related to response to opioids:

In recent years, the observation that the response of patients to opioid drugs may be influenced by properties inherent in the pain or pain syndrome, such as its pathophysiology, has evolved into the belief that certain types of pain, e.g., neuropathic pains, may be unresponsive to these drugs. 

They introduced an experimental paradigm to evaluate opioid responsiveness, related to neuropathic pain, and analysed the analgesic responses to opioid infusion in 28 patients with neuropathic pains. From this analysis, they stated that a neuropathic mechanism may reduce opioid responsiveness, but does not result in an inherent resistance to these drugs.  ^[14] 

Merskey, H. and Bogduk, N., Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms, IASP Press, Seattle, 1994. 

JMKH and DJK under construction 

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