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, anticonvulsants, 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 postherpetic neuralgia (see Symptoms and Signs), root avulsions, painful traumatic mononeuropathy, painful polyneuropathy (particularly due to diabetes—see Diabetic neuropathy), central pain syndromes (potentially caused by virtually any lesion at any level of the nervous system), postsurgical pain syndromes (eg, postmastectomy syndrome, postthoracotomy syndrome, phantom limb pain), and complex regional pain syndrome (reflex sympathetic dystrophy and causalgia—see Complex Regional Pain Syndrome).
Peripheral nerve injury or dysfunction can result in neuropathic pain. Examples are mononeuropathies (eg, carpal tunnel syndrome, radiculopathy), plexopathies (typically caused by nerve compression, as by a neuroma, tumor, or herniated disk), and polyneuropathies (typically caused by various metabolic neuropathies—see Table: Some Causes of Peripheral Nervous System Disorders). Mechanisms presumably vary and may involve an increased number of Na 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 postherpetic neuralgia, central pain (pain after CNS injury), and phantom limb pain (pain felt in the region of an amputated body part—see Complications). 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
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. Symptoms are long-lasting, typically persisting after resolution of the primary cause (if one was present) because the CNS has been sensitized and remodeled.
- 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.
- Multimodal therapy (eg, psychologic treatments, physical methods, antidepressants or anticonvulsants, sometimes surgery)
Without concern for diagnosis, rehabilitation, and psychosocial issues, treatment 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.
Several classes of drugs are moderately effective (see Table: Drugs for Neuropathic Pain; see also the EFNS (European Federation of Neurological Societies) guidelines on the pharmacological treatment of neuropathic pain: 2010 revision ), but complete or near-complete relief is unlikely. Antidepressants and anticonvulsants are most commonly used. Evidence of efficacy is strong for several antidepressants and anticonvulsants.
Opioid analgesics can provide some relief but are generally less effective than for acute nociceptive pain; adverse effects may prevent adequate analgesia. Topical drugs and a lidocaine-containing patch may be effective for peripheral syndromes.
Other potentially effective treatments include
- Spinal cord stimulation by an electrode placed epidurally for certain types of neuropathic pain (eg, chronic leg pain after spine surgery)
- Electrodes implanted along peripheral nerves and ganglia for certain chronic neuralgias
- Sympathetic blockade, which is usually ineffective, except for some patients with complex regional pain syndrome