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  • Updated 02.26.2021
  • Released 01.10.2000
  • Expires For CME 02.26.2024

Central neuropathic pain



Neuropathic pain is defined as pain initiated or caused by a primary lesion or dysfunction in the nervous system. This clinical article discusses the pathophysiology of central neuropathic pain and its classification and differentiation from peripheral neuropathic pain. There is no satisfactory treatment, but various strategies, both pharmacological and nonpharmacological (including motor cortical stimulation) therapies as well as cell and gene therapies, have been used.

Key points

• Central neuropathic pain is associated with CNS lesions, eg, stroke and spinal cord injury.

• Pathophysiology and management of central neuropathic pain is different from that of nociceptive pain.

• Treatment of central neuropathic pain is still a great challenge.

• Several drugs are used with variable degree of effect on neuropathic pain.

• Neurosurgical procedures such as deep brain stimulation and spinal cord stimulation have been used in intractable cases of central neuropathic pain.

Historical note and terminology

Definitions. Neuropathic pain has been defined by the International Association for the Study of Pain Task Force as "pain initiated or caused by a primary lesion or dysfunction in the nervous system" (38). A less commonly used term is “neurogenic pain.” The involvement of the nervous system can be at various levels: nerves, nerve roots, and central pain pathways in the spinal cord and the brain. “Central neuropathic pain” is a term used to describe pain initiated or caused by a primary lesion or dysfunction in the central nervous system and can be included under the broad term of “neuropathic pain.” Neuropathic pain is distinct from nociceptive pain (nonneural tissue damage), occurring when receptors sensitive to tissue damage (nociceptors) are excited by an appropriate stimulus. Neuropathic pain is a form of chronic pain that is persistently generated and serves no beneficial function for the affected individual.

Historical note. Although pain has been known to mankind throughout recorded history, little mention is made of the relation of pain to injury of the nervous system. The first record of neuropathic pain due to injury to the sciatic nerve was provided by the Italian physician Cotunno in 1767 (46). The term “neuralgia” was used in the earlier part of the 18th century for pain due to any damaged nerve. Richard Bright was the first to recognize the segmental nerve distribution of Herpes zoster in 1831, and clinicopathological correlation by demonstration of damage within the dorsal root ganglia was carried out by Von Barenspring in 1862 (01). Mitchell and colleagues described causalgia in 1864 (39). In the beginning of the 20th century, 2 French physicians, Dejerine and Roussy, discovered and described the clinical and pathological features of the thalamic syndrome (10). Occlusion of the posterior cerebral artery as a cause of thalamic syndrome was described 20 years later (12). The terms “thalamic pain” and “thalamic syndromes,” which have been used in past because of the involvement of thalamus, are now obsolete.

Central pain in syringomyelia and allodynia was first described in 1923 (52). Clinical features of central pain were reviewed in a series of lectures and case presentations by George Riddoch in 1938 and are still worth reading for the classical description (47). He defined central pain as, "spontaneous pain and painful overreaction to objective stimulation, resulting from lesions confined to the substance of the central nervous system, including dysesthesia of a disagreeable kind." The first recorded surgical procedure for relief of central thalamic pain, a spinothalamic cordotomy, was performed by Frazier in 1937 (13).

In the 1930s Lewis and Hardy conducted experimental work to explain the underlying mechanisms of hyperalgesia and hyperesthesia (35; 24). In the 1950s clinical experience of several physicians further elaborated the findings in neuropathic pain (43). Although there have been advances in understanding the pathophysiology of pain and several new methods of treatment, management of neuropathic pain remains a difficult problem.

Classification. No satisfactory and comprehensive classification of neuropathic pain exists. This term is sometimes used only for pain due to peripheral neuropathy and excludes central pain because of the differences in clinical features and pathomechanisms. However, according to the definition, the term “neuropathic” applies to all parts of the nervous system. A practical and simplified classification is shown in Table 1 as a basis for discussion of the pathophysiology, as well as for outlining the strategies for management. This is a mix of anatomical levels and causes. The division between central and peripheral neuropathic pain is not so well demarcated because several painful peripheral lesions produce changes in the central nervous system, and some diseases involve both the central and the peripheral nervous systems.

Table 1. A Practical Classification of Neuropathic Pain

Predominantly peripheral neuropathic pain

Lesions of peripheral nerves due to several causes, including the following:

• Systemic diseases (eg, diabetic neuropathy)
• Drug-induced disorders (eg, neuropathy due to chemotherapy)
• Metabolic or nutritional disorders: alcoholic neuropathy, burning feet syndrome
• Traumatic and entrapment syndromes
• Peripheral nerve injuries during general surgical procedures
• Inflammatory demyelinating polyradiculoneuropathy
• HIV sensory neuropathy

Lesions of nerve roots and posterior ganglia:

• Postherpetic neuralgia
• Nerve root avulsions

Lesions of cranial nerves:

• Cranial neuralgias (eg, trigeminal neuralgia)

Neuropathic cancer pain:

• Compression of peripheral nerves, nerve plexuses, and nerve roots
• Paraneoplastic peripheral neuropathy and ganglionopathy
• Complication of cancer therapies (ie, chemotherapy, radiation, and surgery)

Complex regional pain syndrome:

• Type 1 (approximately corresponding to what has been known as reflex sympathetic dystrophy)
• Type 2 (approximately corresponding to causalgia)

Predominantly central neuropathic pain (central pain)

Supraspinal central neuropathic pain -- cerebral lesions, predominantly thalamic but may involve suprathalamic and infrathalamic regions:

• Poststroke pain

- thalamic infarction
- brainstem infarction
- subarachnoid hemorrhage

• Cerebral venous thrombosis
• Cerebral tumors or abscesses compressing the thalamus or brainstem
• Traumatic brain injury
• Multiple sclerosis
• Parkinson disease
• Following thalamotomy for movement disorders

Spinal central neuropathic pain:

• Spinal cord injury
• Complications of anterolateral cordotomy and commissural myelotomy
• Following resection of spinal intramedullary tumors (42)
• Ischemic lesions: anterior spinal artery syndrome and Wallenberg syndrome
• Syringomyelia
• Radiation myelopathy
• HIV myelopathy

Most of the peripheral neuropathies have been described elsewhere in MedLink Neurology. The emphasis in this clinical summary will be on central neuropathic pain. Phantom limb pain is a category by itself and is described separately.

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