Overview of neuropathic pain: syndromes, symptoms, signs, and mechanisms

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Overview of neuropathic pain: syndromes, symptoms, signs, and mechanismsRobert H Dr. DworkinRochester College dental school of medicine phar


Overview of neuropathic pain: syndromes, symptoms, signs, and mechanisms

Robert H Dr. Dworkin

Rochester College dental school of medicine pharmacy department of Anesthesiology, Rochester, New York, United States

Abstract: Objective: to present an overview of the neuropathic pain syndrome, its characteristic symptoms and signs, and the methods to determine its pathophysiology recently

Design: a review of clinical research on neuropathic pain recently. Chronic neuropathic pain syndrome is a severe challenge to clinicians because of its long and often disabling conditions compared with acute pain. The research literature suggests that peripheral neuropathic pain syndrome more than central pain, such as research on the syndrome of postherpetic neuralgia and diabetic neuropathic pain disease provides the basis for the existing knowledge of neuropathic pain.

Conclusion: Although the accurate estimation of neuropathic pain prevalence is not possible, but chronic neuropathic pain may be more common than generally realized, can imagine increasing its popularity will be the future. A large number of data shows that the process of peripheral and central drive many chronic neuropathic pain syndrome, and these different mechanisms can be explained with differences in the nature of the symptoms and signs of experience. Existing methods for the treatment of neuropathic pain is limited and more to alleviate the suffering of patients, incentives are studied on the different inspection to prevent neuropathic pain.

Neuropathic pain is defined as "the International Association for the study of pain in primary lesions or due to nervous system dysfunction or pain." (1) in the nervous system disease or dysfunction of neuropathic pain can be seen mainly in the peripheral or central based on primary disease. As with other types of pain, acute and chronic neuropathic pain were divided, the latter usually think the pain lasts more than normal healing time of 3 months or more. Unfortunately, most patients with neuropathic pain have chronic pain.

In this paper, I outline the neuropathic pain syndrome, their characteristic symptoms and signs, and the recent method to determine the pathophysiological mechanism. Peripheral neuropathic pain because it is generally stressed, and by the ratio of central neuropathic pain more research attention. Key and special part of this article is the chronic neuropathic pain, because of the long-term and often disabling syndrome that clinicians currently facing greater challenges of acute pain.

Table 1. Neuropathic pain syndrome

Peripheral nerve pain syndrome

Chemotherapy induced neuropathy

Complex regional pain syndrome

HIV sensory neuropathy

Secondary to tumor infiltrating neuropathy

Painful diabetic neuropathy

Phantom limb pain


Post mastectomy pain

Trigeminal neuralgia

Central nervous pain syndrome

Central post-stroke pain

The pain of multiple sclerosis

The pain of Parkinson's disease

Spinal cord pain


Table 1 lists the common neuropathic pain syndrome, divided into peripheral and central neuropathic pain syndrome, including patients with non neuropathic pain and neuropathic pain in cancer cancer. There are many causes of neuropathic pain. These include infection, trauma, metabolic abnormalities, chemotherapy, surgery, radiotherapy, neurotoxin, nerve compression, inflammation, tumor invasion. Table 1 lists the peripheral and central neuropathic pain syndromes, but both peripheral and central mechanisms may contribute to the persistent pain of many syndromes.

Although there are a lot of neuropathic pain syndrome, most research on the mechanism and treatment for neuropathic pain or neuropathic pain after herpes zoster ((PHN) or diabetic neuropathic pain (PDN) has been verified. It is generally believed that the two peripheral neuropathic pain syndrome of acquired knowledge has important details of the prompt to understand other neuropathic pain syndrome and treatment mechanism. However, all of these neuropathic pain syndrome is common pathophysiologic mechanisms and the degree of similar pharmacological and non pharmacological response is still unknown.

A few years ago, Bennett (2) are listed in Table 1 provides many neuropathic pain syndromes about incidence, his conclusion is that if the United States, including neuropathic pain, neuropathic pain occurred about 3 million 800 thousand people. Although chronic neuropathic pain may be higher than the rate of common concern, but the accurate estimation of neuropathic pain is not possible. As Schmader (3) recorded after the epidemiology of herpes zoster neuropathic pain and diabetic neuropathic pain review in second pieces of special chapters in the United States, there may be more than 3 million of diabetic patients with neuropathic pain. According to a survey conducted in the United Kingdom, Bowsher (4) recently calculated that in the United States there may be as many as 1 million cases of Xing Tengtong's disease after herpes zoster.

Symptoms and signs

The next is to discuss the role of symptoms and signs in the pathophysiology of neuropathic pain is determined more and more attention. (5-8) it is important to consider the spontaneous pain of neuropathic pain symptoms and signs no stimulation to distinguish stimulus evoked pain and. Spontaneous pain occurs in the absence of any stimulus, which can be continuous or intermittent. Most of the patients described spontaneous pain more than one, that is to say, there are several different characteristics of their pain (such as burning, beating, shooting). Spontaneous persistent pain occurred in all or almost all of the time, but the patient reported typical intensity was different. The onset of spontaneous intermittent pain is fragmented and usually has a relatively short duration of attack. This type of neuropathic pain is often described as patients with paroxysmal and shoot, stab, or shock characteristics.

Second types of neuropathic pain is induced by multiple pain (also known as the stimulus dependent pain). See from table 2, different types of stimuli including allodynia (pain is the pain of normal painless stimuli (hyperalgesia), enhance normal pain reaction of the pain that stimulation), stimulus evoked pain stimulation is divided into many types according to the type, including heat, vibration, activity and rest the (dot or blunt). Dynamic allodynia by brush or cotton swab across the skin to rest pain, finger gently blunt pressure or with von Frey filament shaped light pressure to bring thermal allodynia can be heated or cooled fork or simple application of ice to assess.

Table 2 names of pain defined by the International Association for the study of pain

Definition of pain

Abnormal pain caused by the stimulation of Allodynia without causing pain

Absence of pain caused by Analgesia stimulation without pain

Hyperalgesia Hyperalgesia increases pain caused by normal stimulation

Hyperesthesia is more sensitive to stimuli, but does not include special feelings

Hyperpathia is a pain syndrome characterized by abnormal pain responses to stimulation, particularly repetitive stimulation, as well as enhanced initiation

Hypoalgesia reduces pain induced by normal pain

Insensitive Hypoesthesia reduced sensitivity to stimuli, but not particularly

Adapted from Merskey and Bogduk. (1)

Patients with neuropathic pain induced by various types of pain pathophysiology provides very important information has reached a consensus. Through the research on the neurophysiology of pain, different mechanisms involved in different stimulation pain and painless reaction is now clear. An important difference is that the A beta fiber optic receptor is activated by a painless mechanical stimulus and that the A Delta and C fiber receptors are activated by normal pain stimuli.

In addition to the spontaneous and evoked pain, neuropathic pain patients often report sensory abnormalities, including insensitive Dysesthesias (abnormal feeling unpleasant) and paresthesia (abnormal paresthesias feel unpleasant). Numbness and paresthesia include itching, numbness, tingling, and needling sensation.

Nature is committed to accuracy assessment of neuropathic pain in recent years has been greatly improved, not only because of the symptoms and signs may provide a potential mechanism, but also because it is necessary to evaluate the response to treatment may more pain than the overall rating value. Although a variety of symptoms and signs are considered characteristics of neuropathic pain, but few systems have comparative study on neuropathic and non neuropathic pain syndrome pain quality, the most commonly used method to check the properties of spontaneous pain is the Gil pain questionnaire (MPQ), which includes: feeling, emotion, description and assessment of pain (10). In order to distinguish between different types of pain including two neuropathic pain syndrome with one of the earliest MPQ, postherpetic neuropathic pain and phantom limb pain. (11) the later using MPQ including indicates that it can distinguish atypical facial pain with trigeminal neuralgia (12) of diabetic neuropathic pain with non divine pain in the leg or foot, (13) different types of peripheral neuropathy with chronic benign pain (14) and chronic spinal cord injury with spinal cord injury. (15)

The results of Boureau (14) provide evidence that six kinds of feeling adjectives significantly often patients with neuropathic pain patients. The six adjectives are electric shock, burning, cold, tingling, tingling, itching. The electric shock, burning and tingling in patients with neuropathic pain (53%, 54% and 48%) is the most common. Provide important clinical information of these results for neuropathic pain clinical diagnosis, because these adjectives in clear recognition of neuropathic pain is particularly valuable. Although several other adjectives is usually characterized as neuropathic pain including tearing pain and shooting can not distinguish between neuropathic and non neuropathic pain patients. A very interesting finding is that all MPQ emotional adjectives are not patients with neuropathic pain, and in some cases very different. For example, 48% non neuropathic pain patients for fear of being recognized, but only 3% patients with neuropathic pain.

In addition to demonstrate its ability to distinguish between different pain syndromes, MPQ is also used to describe the changes over time in patients with specific characteristics of neuropathic pain. For example, the nature of acute herpes zoster neuralgia after herpes zoster with nature of chronic neuropathic pain. (16, 17), are considered in the sharp sting in patients with acute herpes zoster than postherpetic neuralgia is common, and the burning pain was seen in postherpetic neuralgia is common has rarely been reported in patients with acute herpes zoster. Unfortunately, these results are based on a cross-sectional study of patients in different groups, rather than prospective studies of the same individual.

Other data suggest that pain and burning pain should be studied in patients with postherpetic neuralgia. An antiviral drug acyclovir treatment of herpes zoster infection after acute herpes zoster neuralgia patients than those who did not receive acyclovir treatment were less likely to report burning pain, and ache were similar in two groups. (17, 18) Boureau found that describe the close relationship between word burning and neuropathic pain. (14) one of these data interpretation is that the mechanism of antiviral treatment of herpes zoster may prevent the development of chronic neuropathic pain.

Because MPQ may be time-consuming for some patients, Melzack (19) develops short form McGill pain questionnaire (SF- MPQ). This measure is used in control of neuropathic pain in clinical trials in the three largest placebo. These experimental studies have reported improvement in SF- MPQ in patients with postherpetic neuralgia (20, 22) and diabetic neuropathic pain () treated with gabapentin.

The MPQ and SF- MPQ is not specifically for the assessment of the development of neuropathic pain. Galer and Jensen (23) recently developed neuropathic pain score (NPS), which is designed for the evaluation of a questionnaire survey format design of the different nature of the neuropathic pain. In the first study of diabetic neuropathic pain effectively, the method of postherpetic neuralgia in patients with neuropathic pain, and 3 other types of complex regional pain syndrome, diabetic neuropathy, and peripheral nerve injury. NPS was also used to successfully evaluate treatment response in a group of patients with central and peripheral neuropathic pain. In a recent study, NPS was used to examine the incidence of pain in patients with peroneal muscular atrophy (CMT) and to compare the pain characteristics of several peripheral nerves with rational pain syndrome. (24) 24 The results of this study show that CMT and postherpetic neuralgia, complex regional pain syndrome, diabetic neuropathy, peripheral nerve injury and pain intensity and pain characteristics were similar and also further support the assessment of the value of NPS in neuropathic pain.

MPQ, SF-MPQ, MPQ and NPS are in clinical trials as a new method for the treatment of neuropathic pain results widely used standard. Although it is still possible to see whether they can respond more sensitively to the severity of the pain. MPQ and NPS evaluation of pain with different characteristics reflect different mechanisms of neuropathic pain has not been verified, it will be the future of another important goal.

Although patients with neuropathic pain symptoms and signs are usually integrated by history and physical examination and self report questionnaire to evaluate quantitative sensory testing (QST) to assume a greater role in the study of neuropathic pain. At QST, our goal is to quantify the extent to which a particular sensation needs to be stimulated, for example, to stimulate the temperature to what extent the thermal pain is reported. Computer control equipment is often used to provide accurate quantification of the stimulus intensity and duration, but also other methods can be used to quantify stimulus parameters (e.g., von Frey filaments). (25)

The use of QST to assess sensory thresholds provides a means for assessing the function of peripheral nerve fibers and their association with the central nervous system. (26) because different fibers are involved in the perception of different types of stimuli, the response to different stimuli is assessed by the specificity of the different fiber bundles. In addition to play an important role in the study of the mechanism of neuropathic pain, (6, 27, 28) QST can be used as a quantitative measure of neuropathic pain symptoms in natural history study (29, 30) - for example, treatment response to report the regional thermal allodynia and neuropathic pain thermal test patients. (31, 33) is discussed in detail the methods of QST and QST and neuropathic pain related found explanation is seen in other articles. (9, 26, 33)

The mechanism of neuropathic pain

Until recently, the relevant information of a main objective is to evaluate the clinical treatment of neuropathic pain symptoms and signs to diagnose the disease or condition has been obtained. In the past few years, there have been an alternative assessment of disease according to neuropathic pain scientific literature and clinical research results. This alternative classification of diseases classifies patients according to their underlying mechanisms of pain. The main goal of this approach is to identify the specific pathophysiological mechanisms of pain in patients and then target these specific mechanisms for targeted therapy. (5-8)

A large number of studies on the mechanisms of animal and human pain promote the validation of this approach. (34, 35) in addition, realize more and more determined by the pain caused by the disease syndrome, such as herpes zoster after neuropathic pain or diabetic neuropathic pain, chronic pain is likely to have a variety of mechanisms. It's not surprising. Different types of nerve injury can be caused by for example, varicella zoster virus herpes zoster or ischemia caused by diabetes, the explanation for herpes zoster neuropathic pain after nerve or diabetic neuropathic pain provides different pathophysiological basis. This view has several implications. One of them is that patients with the same disease often have different pain mechanisms which are reflected in different symptoms and signs. Because has a heterogeneous group of neuropathic pain syndrome patients have different mechanisms and symptoms, so the treatment response and prognosis of different.

This heterogeneity may be a subtype of patients with different concepts. (6, 27) or coexisting in patients with multiple mechanisms, as demonstrated by their different degrees of pain. Patients with different diseases may therefore be pain mechanisms than other patients with the same diseases have more similar to each other. For example, a herpes zoster patients with neuropathic pain and diabetic neuropathic pain as pain mechanism (such as central sensitization, but the feeling) and another due to different mechanisms (e.g. central reorganization) patients with neuropathic pain caused by herpes zoster after different.

Although a number of research institutions confirmed the potential route mechanism, present clear special mechanisms of neuropathic pain in patients with symptoms and signs are not possible. In addition, a few sample control experiments to implement special mechanism of patients with neuropathic pain treatment. The current target controlled clinical study by symptoms and signs, QST and pathological response (6, 8, 36) to clear the mechanism of pain, so it seems clear neuropathic pain mechanisms and to their target controlled treatment will happen big leap.

It is generally believed that the peripheral and central process and promote the development of neuropathic pain syndrome, and these different mechanisms

Can explain the different characteristics of the symptoms and signs of experience. By Rowbotham and Fields6 (27), one of the best examples on mechanism based approach to the proposal in the treatment of neuropathic pain is at least three different mechanisms involved in postherpetic neuralgia, and these mechanisms are reflected in the three different subtypes of patients.

Patients with Rowbotham and Fields (6, 27) identified in the first group had significant allodynia and small sensory deficits. In these patients, severe acute herpes zoster pain begins with central sensitization and then maintains the primary afferent nociceptive receptor. These patients respond to local anesthetics, which may impair the abnormal activity of the nociceptive receptors. The second group includes those from patients with little or no pain, allodynia, and pain in the most obvious areas of feeling inadequate. These patients with primary afferent nociceptors feel the pain seems to be minimal, suggesting that they are spontaneous pain caused by different mechanisms, perhaps the central nerve hyperexcitability results.

The third group includes those who feel inadequate and pain in patients with abnormal symptoms and signs of this model can explain deafferentation with central reorganization by another mechanism (involving large myelinated fibers sprouting into the substantia gelatinosa, where exposure to spinal cord neurons, here only nociceptor dominance.) (37) despite evidence that central sensitization and other mechanisms in the treatment of post herpetic neuralgia pathophysiology has played an important role is the most clear, like many other mechanisms involved in peripheral neuropathic pain syndrome.

Future direction

Neuropathic pain is prevalent in the next few years is expected to increase for several reasons. One is the aging of the population, some neuropathic pain syndrome in the elderly is more common, including herpes after diabetic neuropathic pain, neuropathic pain, and central post-stroke pain. Another reason is that often cause neuropathic pain of cancer, HIV infection, diabetes and other diseases in patients with longer survival. Finally, the medical and surgical intervention for the treatment of neuropathic pain can cause cancer and other diseases, and these interventions are more frequently used, this is not only because the patients live longer, but also because of the development of new therapies.

Although a substantial increase in the prevalence of neuropathic pain is a major public health problem, this increase may be offset by other recent development situation. Watson (38) recently noted that "as far as possible, the best treatment available to patients with as much as half of patients suffering from postherpetic neuralgia is incomplete or completely refractory." And because of this, we believe that early and aggressive treatment is necessary to prevent such an obstacle." The existing methods of treating all other neuropathic pain syndrome as treatment of postherpetic neuralgia has limitations, but not for many patients to provide relief to stimulate us to pay more attention to prevention of neuropathic pain.

To prevent neuropathic pain including examples of ongoing clinical trials to test whether varicella vaccine prevention of herpes zoster immune to the elderly (39) and whether patients with pre treatment of herpes zoster has been proved to be effective drugs for treatment of herpes zoster neuralgia, for example, antiepileptic drugs, tricyclic antidepressants, and opioid analgesics that can prevent postherpetic neuropathic pain. (40-42) in addition, due to improved glycemic control in diabetic patients has been shown to delay the onset and progression of diabetic neuropathic pain (43), it can be thought to prevent the development of diabetic neuropathic pain. Finally, a more effective management strategy of preemptive analgesia may prevent phantom limb and breast pain and other development of neuropathic pain syndrome after surgery. (44, 45)

Pay attention to prevent neuropathic pain and the pharmaceutical industry to develop new methods for treatment of neuropathic pain is of great interest for the future neuropathic pain provides a basis for optimism. However, many patients with neuropathic pain is the best therapy can provide complete resistance to treatment." This is a special part in the "influence of neuropathic pain on patients and the society of literature shows more effective prevention and treatment of neuropathic pain is great strategy. Schmader (3) epidemiology and natural history of diabetic neuropathic pain and neuropathic pain are reviewed after herpes zoster, and discuss the implications of these common neuropathic pain syndrome to individuals suffering and to society. Thompson (46) to investigate the drug facing economic model in the development of neuropathic pain challenge, not only because of the costs of neuropathic pain is limited, but also because of the natural history and response to treatment of severe chronic pain caused by fluctuations. Finally, Turk47 reviews the literature on the effectiveness of chronic pain and evaluates the different perspectives.

Chronic neuropathic pain and other chronic pain syndrome caused by psychological distress, physical disability, reduced quality of life, and increased health and social costs. An important theme of this special section is the benefits and cost-effectiveness of different personal and social costs make the clinical evaluation of treatment of chronic neuropathic pain caused by complex. The Turks (47) provides a general treatment of the chronic pain review data, but these data as pointed out by Thompson (46) is not particularly for neuropathic pain. Of course, there are a lot of information about epidemiology, natural history, clinical response and received benefit cost must be collected, it may be fully aware of the influence of patients with neuropathic pain before and on society.


Backonja and Galer provide a proper conclusion and the rest of the content of the introduction, (48) they have recently stressed that "the rule is nothing more than chronic neuropathic pain patients had more than one type of pain. In such a high and chest herpes zoster neuropathic pain after men may continue to pain, let him awake all night; the mechanical allodynia and hyperalgesia so that he can't wear any clothes that he cannot and social activities; secondary shoulder myofascial pain to arm use is limited; with just a few weeks later the patients are pain, sleep deprivation, depression and anxiety, very impatient."

This quote is a compelling suggest that chronic pain can have profound adverse impact on the quality of life, although a multidisciplinary approach, including physical therapy and psychological intervention and care in the treatment of chronic pain is of great value. No study reported the specific test in patients with neuropathic pain. Nevertheless, there is no doubt that a multidisciplinary method provides significant benefits for neuropathic pain, as it was studied in all other chronic pain syndrome.

Thanks: Paul Roland and Mary Gracie AF for the preparation of this article to help and get a special section of great concern.


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