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Neuropathic Pain


James C. Watson

, MD, Mayo Clinic College of Medicine and Science

Last full review/revision Feb 2020
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Neuropathic pain results from damage to or dysfunction of the peripheral or central nervous system, rather than stimulation of pain receptors. Diagnosis is suggested by pain out of proportion to tissue injury, dysesthesia (eg, burning, tingling), and signs of nerve injury detected during neurologic examination. Although neuropathic pain responds to opioids, treatment is often with adjuvant drugs (eg, antidepressants, antiseizure drugs, baclofen, topical drugs).

Pain can develop after injury to any level of the nervous system, peripheral or central; the sympathetic nervous system may be involved (causing sympathetically maintained pain). Specific syndromes include

Etiology of Neuropathic Pain

Peripheral nerve injury or dysfunction can result in neuropathic pain. Examples are

Mechanisms presumably vary and may involve an increased number of sodium channels on regenerating nerves.

Central neuropathic pain syndromes appear to involve reorganization of central somatosensory processing; the main categories are deafferentation pain and sympathetically maintained pain. Both are complex and, although presumably related, differ substantially.

Deafferentation pain is due to partial or complete interruption of peripheral or central afferent neural activity. Examples are

Mechanisms are unknown but may involve sensitization of central neurons, with lower activation thresholds and expansion of receptive fields.

Sympathetically maintained pain depends on efferent sympathetic activity. Complex regional pain syndrome sometimes involves sympathetically maintained pain. Other types of neuropathic pain may have a sympathetically maintained component. Mechanisms probably involve abnormal sympathetic-somatic nerve connections (ephapses), local inflammatory changes, and changes in the spinal cord.

Symptoms and Signs of Neuropathic Pain

Dysesthesias (spontaneous or evoked burning pain, often with a superimposed lancinating component) are typical, but pain may also be deep and aching. Other sensations—eg, hyperesthesia, hyperalgesia, allodynia (pain due to a nonnoxious stimulus), and hyperpathia (particularly unpleasant, exaggerated pain response)—may also occur.

Patients may be reluctant to move the painful part of their body, resulting in muscle atrophy, joint ankylosis, and limited movement.

Symptoms are long-lasting, typically persisting after resolution of the primary cause (if one was present) because the CNS has been sensitized and remodeled.

Diagnosis of Neuropathic Pain

  • Clinical evaluation

Neuropathic pain is suggested by its typical symptoms when nerve injury is known or suspected. The cause (eg, amputation, diabetes) may be readily apparent. If not, the diagnosis often can be assumed based on the description. Pain that is ameliorated by sympathetic nerve block is sympathetically maintained pain.

Treatment of Neuropathic Pain

  • Multimodal therapy (eg, psychologic treatments, physical methods, antidepressants or antiseizure drugs, neuromodulation, sometimes surgery)

Without concern for diagnosis, rehabilitation, and psychosocial issues, treatment of neuropathic pain has a limited chance of success. For peripheral nerve lesions, mobilization is needed to prevent trophic changes, disuse atrophy, and joint ankylosis. Surgery may be needed to alleviate compression. Psychologic factors must be constantly considered from the start of treatment. Anxiety and depression must be treated appropriately. When dysfunction is entrenched, patients may benefit from the comprehensive approach provided by a pain clinic.


Topical drugs and a lidocaine-containing patch may be effective for peripheral syndromes.

Other potentially effective treatments include

Treatment reference

Key Points

  • Neuropathic pain can result from efferent activity or from interruption of afferent activity.

  • Consider neuropathic pain if patients have dysesthesia or if pain is out of proportion to tissue injury and nerve injury is suspected.

  • Treat patients using multiple modalities (eg, psychologic treatments, physical methods, neuromodulation, antidepressants or antiseizure drugs, analgesics, surgery), and recommend rehabilitation as appropriate.

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