Symposium on pain medicine
Neuropathic Pain: Principles of Diagnosis and Treatment

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Abstract

Neuropathic pain is caused by disease or injury of the nervous system and includes various chronic conditions that, together, affect up to 8% of the population. A substantial body of neuropathic pain research points to several important contributory mechanisms including aberrant ectopic activity in nociceptive nerves, peripheral and central sensitization, impaired inhibitory modulation, and pathological activation of microglia. Clinical evaluation of neuropathic pain requires a thorough history and physical examination to identify characteristic signs and symptoms. In many cases, other laboratory investigations and clinical neurophysiological testing may help identify the underlying etiology and guide treatment selection. Available treatments essentially provide only symptomatic relief and may include nonpharmacological, pharmacological, and interventional therapies. Most extensive evidence is available for pharmacological treatment, and currently recommended first-line treatments include antidepressants (tricyclic agents and serotonin-norepinephrine reuptake inhibitors) and anticonvulsants (gabapentin and pregabalin). Individualized multidisciplinary patient care is facilitated by careful consideration of pain-related disability (eg, depression and occupational dysfunction) as well as patient education; repeat follow-up and strategic referral to appropriate medical/surgical subspecialties; and physical and psychological therapies. In the near future, continued preclinical and clinical research and development are expected to lead to further advancements in the diagnosis and treatment of neuropathic pain.

Section snippets

Neuropathic Pain Mechanisms Relevant to Diagnosis and Treatment

As illustrated in the Figure, an understanding of the diverse mechanisms of pain transmission and pain modulation is crucial for appropriate clinical assessment as well as the development and application of analgesic therapies. Development of several preclinical pain models involving injury (eg, surgical), or disease induction (eg, streptozocin-induced diabetic neuropathy), of peripheral or central neurons has facilitated many sophisticated investigations, providing a wealth of information

Primary Care Approach to Neuropathic Pain Assessment

In the setting of clinical care for a patient suspected of having neuropathic pain, careful history and physical examination and special laboratory tests serve to (1) aid in formulating a differential diagnosis of the presenting problem, (2) guide appropriate treatment selection, and (3) follow-up individual responses to treatment.32, 33, 34 Diagnosis of neuropathic pain is primarily based on history and physical examination although other special investigations are often useful.6, 32 Clinical

Quantitative Sensory Testing

Patients with neuropathic pain suffer from various sensory abnormalities that can occur in different combinations. It is thought that sensory signs and symptoms are closely linked to underlying mechanisms of pain generation, and it is therefore likely that precise analysis of the individual somatosensory pattern might facilitate a mechanism-based treatment strategy. Thus, it is important to assess the individual sensory phenotype as precisely as possible. In addition to the self-report

Other Special Tests

Clinical neurophysiological examinations are vital assessment tools in establishing a diagnosis of neuropathic pain with peripheral nerve involvement.55 However, clinical neurophysiology examines large fibers but is generally not useful in determining the possible involvement of small nerve fibers in neuropathic pain conditions. A number of other tests can be performed in patients with suspected small-fiber neuropathy. Apart from clinical and electrophysiological examination, other assessments

Overview of Treatment Goals and Strategies in Neuropathic Pain

In addition to symptom control, management of patients with neuropathic pain requires periodic reevaluation to rule out other treatable underlying medical conditions, patient education, and reassurance. Education about the natural history of the patient’s underlying neuropathic condition as well as the limitations of currently available pain treatments helps generate appropriate treatment expectations; that is, current therapies are often not curative, and residual pain, even during treatment,

Drug Therapy for Neuropathic Pain

Various drug classes with analgesic effects have been compared to placebo in clinical trials involving patients with various neuropathic pain conditions including antidepressants, anticonvulsants, local anesthetic drugs, NMDA receptor antagonists, opioids, cannabinoids, botulinum toxin, topical capsaicin, and other agents.70 Several of these drugs were first developed for other indications (eg, depression and epilepsy) and subsequently evaluated in neuropathic pain. Systematic review and

Interventional Management of Neuropathic Pain

Given that our treatment-related focus is on pharmacological therapy, an in-depth review of interventional management is beyond the scope of this review. However, we provide some brief comments here in context of other treatment modalities. Patients with neuropathic pain often do not respond adequately to pharmacologic treatments used alone or in combination with nonpharmacologic treatments and their pain is therefore called refractory.96 Before patients continue endless pharmacological

Central Pain

Central pains are conditions caused by a lesion or disease affecting the somatosensory system within the CNS.1 The diseases or lesions giving rise to central neuropathic pain are multiple and include stroke, multiple sclerosis, a syrinx within the cord or the brain stem, and an injury to the spinal cord. Even pains experienced by patients with Parkinson disease have been suggested to represent a central neuropathic pain state. Central pains are not rare. For example, central poststroke pain,

Conclusion

A diverse array of clinical conditions cause neuropathic pain in both the peripheral and central nervous systems. Several features of clinical presentation (eg, development of pain after nervous system injury/disease, certain pain quality descriptors, allodynia, and sensory loss) and treatment response (eg, to anticonvulsant drugs) indicate that neuropathic pain is fundamentally different from inflammatory or nociceptive conditions such as osteoarthritis. Given the association between

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  • Cited by (0)

    Grant Support: This work was supported in part by the Canadian Institutes of Health Research (grant no. MSH-55041 awarded to Dr Gilron).

    Potential Competing Interests: Dr Jensen has received financial support from Pfizer, Grunenthal, Orion and Astellas as compensation for participating as consultant.

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