Neuropathic pain syndromes typically have both negative and positive sensory symptoms and signs.3Nonsensory neurological symptoms and signs depend on the underlying cause and may independently contribute to pain and disability. Although neuropathic pain has been defined by the International Association for the Study of Pain as pain "initiated or caused by a primary lesion or dysfunction in the nervous system,"4(p212) several investigators have recently argued that the inclusion of the term dysfunctionmakes this definition vague and unacceptably broad.5,6 A proposed solution is to define neuropathic pain as pain caused by a lesion of the peripheral or central nervous system (or both) manifesting with sensory symptoms and signs.6 Underlying causes include infections, trauma, metabolic abnormalities, chemotherapy, surgery, irradiation, neurotoxins, inherited neurodegeneration, nerve compression, inflammation, and tumor infiltration. Demonstrating a lesion of the nervous system compatible with particular symptoms and signs provides strong support for considering the pain to be neuropathic. However, when no lesion can be demonstrated, the limits of current diagnostic technology do not always allow the possibility of neuropathic pain to be excluded. The diagnosis of neuropathic pain is based on a medical history, review of systems, physical and neurological examination, and appropriate laboratory studies including blood and serologic tests, magnetic resonance imaging, and electrophysiologic studies.3 In some instances, nerve or skin biopsy is necessary to directly visualize nerve fibers.
Evaluation of Pain and Other Symptoms
The assessment of pain and other symptoms is needed for diagnosis and to guide therapy. No single symptom or sign is pathognomonic. Because neuropathic pain is the result of disease or injury to the nervous system, clinical manifestations typically include both negative and positive sensory symptoms and signs. Motor symptoms and signs are often present, but these deficits can be very subtle.
A distinction should be made between stimulus-evoked pain and spontaneous (stimulus-independent) pain, which may have different underlying mechanisms.7 Spontaneous pain can be either constant or intermittent (even paroxysmal), and most patients describe having both (eg, constant "burning" pain plus intermittent pain that is "shooting" or "electric shock–like"). In addition, spontaneous paresthesias and dysesthesias manifest as abnormal sensations, including crawling, numbness, itching, and tingling. When obtaining the patient's history, it is important to assess the intensity, quality, and duration of spontaneous pain and abnormal sensations. The topographical distribution is especially helpful in guiding the neurological examination.
Pain may be evoked by everyday environmental stimuli such as the gentle touch and pressure of clothing, wind, riding in a car, and hot and cold temperatures. Common neurological examination tools, including a cotton wisp, a foam brush, a tuning fork, and cold and warm water–filled tubes, can be used to mimic these stimuli.
Pain intensity can be rated with any of several reliable and validated verbal, numerical, or visual analog scales. Patients rate their pain using some type of continuum (eg, "no pain" to "worst possible pain").8 The often unusual abnormal sensations in patients with neuropathic pain can be assessed with measures of pain quality such as the Neuropathic Pain Scale9 and Neuropathic Pain Questionnaire.10 Chronic pain has a significant negative effect on quality of life, and various measures of physical and emotional function can also be used to evaluate a patient's response to treatment.11 Assessment of psychological comorbidity (eg, depression or anxiety), sleep disturbance, work-related issues, treatment expectations, rehabilitative needs, and the availability of social support from family and friends should not be overlooked.12
Physical Examination
A thorough physical and neurological examination can help determine where the lesion is and assess nonneuropathic contributions to the patient's pain, most commonly musculoskeletal, inflammatory, myofascial, and psychological processes.3 When combined with a history and laboratory tests suggesting a specific cause, the finding of negative and positive sensory phenomena in the same area innervated by damaged nervous system pathways usually confirms the diagnosis.
Patients may have sensory deficits with one modality, such as pinprick sensitivity, and hyperalgesia to another, such as light touch, in the same nerve distribution. Whereas the physician may have difficulty recognizing this paradoxical finding, patients are even more confused by the complexity of their sensory experiences; they often have trouble describing the unusual nature of their symptoms and fear that they will not be believed. For patients to be good sensory witnesses and provide all of the necessary information, they need to be reassured as well as instructed to carefully describe their symptoms and rate the severity of their abnormal sensations. When specific stimuli in the standard neurological sensory examination are applied first to the unaffected area and then to the area affected by pain, patients should be instructed to first respond in simple terms—that is, whether the stimulus applied to the painful area causes the same sensation as in the unaffected area or whether it is less or more intense—before describing their perception of the quality of the stimulus. For example, pinprick may be more painful (hyperalgesia) but less sharp because of the underlying sensory deficit.
Pain in response to a normally nonnoxious stimulus is termed allodynia. Dynamic mechanical allodynia can be elicited by lightly rubbing or brushing the skin with a cotton swab or brush, static mechanical allodynia can be provoked by blunt pressure with a finger, and thermal allodynia can be assessed with a warm or cool tuning fork. An increased sensation of pain in response to a normally painful stimulus is termed hyperalgesia, which can be assessed using painful thermal (cold or heat) or punctate (eg, pinprick) stimuli. Painful summation and hyperpathia to repeated stimuli, especially when the initial sensation is reduced, is important evidence of abnormal sensory processing.
Nonsensory neurological and musculoskeletal symptoms may contribute strongly to overall disability. Motor system symptoms and signs include weakness, fatigability, hypotonia, tremor, dystonia, spasticity, ataxia, apraxia, and motor neglect. Other musculoskeletal symptoms and signs include decreased range of motion, stiffness of joints, spontaneous muscle spasms, localized muscle tenderness, and myofascial trigger points.
Ancillary Studies
There is no single diagnostic test for neuropathic pain or pain in general. Ancillary studies can confirm or exclude underlying causes and suggest disease-specific treatments, such as for diabetes mellitus in patients with painful neuropathy or spinal disorders in patients with radiculopathy. To assess peripheral nerve function, nerve conduction velocity tests and electromyography provide information about large myelinated peripheral nerve function but do not test smaller myelinated or unmyelinated nerve fibers carrying pain and temperature information. Quantitative thermal sensory testing relies on the patient's psychophysical ability to discriminate between fine changes in thermal stimuli; it is not widely used because it requires specialized equipment and training. Magnetic resonance imaging assesses anatomical integrity of thermonociceptive sensory-processing regions such as the brainstem, thalamus, sensory cortex, anterior cingulate, and insular cortex, which can contribute to central neuropathic pain when injured. Functional magnetic resonance imaging can further assess these and other pain-related structures, but its role in clinical practice will remain limited in the near future.
Diagnosing neuropathic pain can be difficult. For example, in radicular neck and low back pain, there is a significant neuropathic component from the nerve root injury, but mechanical instability or secondary myofascial pain may mask this component. Physicians should also keep in mind that psychosocial factors are a major component of the experience of chronic pain and should be routinely addressed when patients are evaluated. Psychological processes such as anxiety can influence the report of pain and in rare instances produce exaggerated responses. However, sincerely communicating that the patient's pain is taken seriously and providing clear instructions will minimize the possibility that the neurological examination is unreliable or uninterpretable because of psychological processes. When combined with a long history of multiple unexplained pain problems, somatization disorder or another psychiatric diagnosis is possible. Proper diagnosis is the cornerstone of effective treatment, and complex patterns of signs and symptoms may necessitate the involvement of multiple medical specialties.