(See also Overview of Pain Overview of Pain Pain is the most common reason patients seek medical care. Pain has sensory and emotional components and is often classified as acute or chronic. Acute pain is frequently associated with anxiety... read more .)
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
Root avulsions
Painful traumatic mononeuropathy
Painful polyneuropathy (including neuropathy due to diabetes Diabetic Nephropathy In patients with diabetes mellitus, years of poorly controlled hyperglycemia lead to multiple, primarily vascular, complications that affect small vessels (microvascular), large vessels (macrovascular)... read more
or chemotherapy)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 Pain in the Residual Limb Over 70% of amputees have postamputation pain in the residual limb, which can severely limit function, impair quality of life, and significantly impede rehabilitation. Residual-limb pain should... read more )
Complex regional pain syndrome Complex Regional Pain Syndrome (CRPS) Complex regional pain syndrome (CRPS) is chronic neuropathic pain that follows soft-tissue or bone injury (type I) or nerve injury (type II) and lasts longer and is more severe than expected... read more (reflex sympathetic dystrophy and causalgia)
Etiology of Neuropathic Pain
Peripheral nerve injury or dysfunction can result in neuropathic pain. Examples are
Mononeuropathies Mononeuropathies Single mononeuropathies are characterized by sensory disturbances and weakness in the distribution of the affected peripheral nerve. Diagnosis is clinical but may require confirmation with electrodiagnostic... read more
(eg, carpal tunnel syndrome Carpal Tunnel Syndrome Carpal tunnel syndrome is compression of the median nerve as it passes through the carpal tunnel in the wrist. Symptoms include pain and paresthesias in the median nerve distribution. Diagnosis... read more , radiculopathy)Plexopathies Brachial Plexus and Lumbosacral Plexus Disorders Disorders of the brachial or lumbosacral plexus cause a painful mixed sensorimotor disorder of the corresponding limb. Because several nerve roots intertwine within the plexus (see figure Plexuses)... read more (typically caused by nerve compression, as by a neuroma, tumor, or herniated disk Herniated Nucleus Pulposus Herniated nucleus pulposus is prolapse of an intervertebral disk through a tear in the surrounding annulus fibrosus. The tear causes pain due to irritation of sensory nerves in the disk, and... read more
)Polyneuropathies Polyneuropathy A polyneuropathy is a diffuse peripheral nerve disorder that is not confined to the distribution of a single nerve or a single limb and typically is relatively symmetrical bilaterally. Electrodiagnostic... read more (typically caused by various metabolic neuropathies—see tables Causes of Peripheral Nervous System Disorders Some Causes of Peripheral Nervous System Disorders The peripheral nervous system refers to parts of the nervous system outside the brain and spinal cord. It includes the cranial nerves and spinal nerves from their origin to their end. The anterior... read more )
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
Central pain (pain after central nervous system [CNS] injury)
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.
Neuromodulation Neuromodulation Nonopioid and opioid analgesics are the main drugs used to treat pain. Antidepressants, antiseizure drugs, and other central nervous system (CNS)–active drugs may also be used for chronic or... read more (spinal cord or peripheral nerve stimulation) is particularly effective for neuropathic pain.
Several classes of drugs are moderately effective (see table Drugs for Neuropathic Pain Drugs for Neuropathic Pain Nonopioid and opioid analgesics are the main drugs used to treat pain. Antidepressants, antiseizure drugs, and other central nervous system (CNS)–active drugs may also be used for chronic or... read more , but complete or near-complete relief is unlikely. Antidepressants and antiseizure drugs are most commonly used. Evidence of efficacy is strong for several antidepressants and antiseizure drugs (1 Treatment reference 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... read more ).
Opioid analgesics Opioid Analgesics Nonopioid and opioid analgesics are the main drugs used to treat pain. Antidepressants, antiseizure drugs, and other central nervous system (CNS)–active drugs may also be used for chronic or... read more 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
Neural blockade or ablation (radiofrequency ablation, cryoablation, chemoneurolysis)
Treatment reference
1. Finnerup NB, Attal N, Haroutounian S, et al: Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 14 (2):162–173, 2015. doi: 10.1016/S1474-4422(14)70251-0.
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.
