Classic Central Pain Syndromes: Review of Neurologic Causes of Pain

Treatment of these very difficult cases involves more than just a medication: a full biopsychosocial intervention is most helpful.
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Editor’s Note: Practical Pain Management has invited Dr. Jay, a leader in the pain management movement, to write an article on the classic central pain syndromes. Why? We feel that physicians would benefit from review of the classic neurologic diseases that gave rise to the term “central pain syndrome.” It is now 100 years after Dr. George M. Gould published An Illustrated Dictionary of Medicine, which was the definitive word on medicine at the time. He defined and described pain simply as, “bodily or mental suffering, distressing or agonizing sensation. It is usually due to irritation of a sensory nerve, although there are said to be pains of central origin.” About 50 years later, the term “central pain syndrome” started to be used to describe the pain after a stroke or concomitantly with a central neurologic disease, such as multiple sclerosis or Parkinson’s disease. Today, we now recognize that any peripheral pain, such as a degenerative spine, arthritic foot, or amputated leg, can transform into central pain. Some diseases like fibromyalgia can begin centrally or peripherally and end up becoming mostly central. The proper diagnosis going forward is simply “central pain.” It is incumbent on every practitioner to know that central pain has been suspected for 100 years, and pain accompanying brain disease has been known for at least 50 years. It is clear that a high percentage of pain treated in practice is “central” regardless of where it originates.

Neuropathic pain has a number of forms or diagnoses, but possibly the most difficult to understand and treat is central neuropathic pain (CNP). The various definitions of neuropathic pain indicate that there is pain caused by a lesion or disease of the somatosensory nervous system. The most common neuropathies, peripheral neuropathies, are often secondary to peripheral, small nerve fiber damage typically in the distal upper and lower extremities. This is in counter-distinction to the origins of CNP. Since there are a number of etiologies of CNP (see Table 1), this article will focus on neurologic diseases that cause central pain.

Table 1. The Classic Pain Syndromes

  • Multiple sclerosis
  • Parkinson’s disease
  • Spinal cord injury
  • Phantom limb pain
  • Post-stroke chronic pain

Multiple Sclerosis
Pain in multiple sclerosis (MS) is very common, with prevalence in patients ranging from 43% to 54%,1 to 86%.2 These patients have different types of pain (in addition to central pain), including dysesthesias in the extremities, complex regional pain, L’Hermitte’s sign, trigeminal neuralgia, painful tonic spasms, and pain secondary to painful tonic spasms.

CNP in MS is thought to be secondary to damage to myelinated nerves in the central nervous system and propagated by two main mechanisms: the generation of ectopic impulses at demyelinated lesions in response to neural damage,3or the removal of modulation of afferent A-δ and C-fiber pain pathways by interruption of inhibitory impulses from the brain.4

The pharmacological treatment of CNP can be broken into several treatment management groups. First-line management includes the use of tricyclic antidepressants (TCAs), gabapentin, or topical lidocaine; second-line management involves combination therapy using opioid analgesics or tramadol along with the first-line medications; and third-line management uses other antiepileptics and antidepressants.5

Parkinson’s Disease
The Parkinson’s disease (PD) patient may experience CNP via stabbing, burning, scalding, or lancinating pain, which is unprovoked in unusual locations such as the face, mouth, genitalia, pelvis, anus, or abdomen.6

A neurophysiological study of CNP in PD patients was done by Schestatsky et al7 who found that while conduction along the peripheral and central pain pathways was normal, with or without primary central pain, there were signs of hyperalgesia, and their patients exhibited a lack of habituation of sympathetic sudomotor responses to repetitive pain stimuli, which suggested an abnormal control of pain on the autonomic centers. These abnormalities were diminished by treatment with levodopa (L-dopa), which suggested that the dysfunction might occur in dopaminergic centers regulating the autonomic functions and inhibitory modulation of pain inputs.

It has been shown that the pharmacologic, electric, and surgical manipulation of the substantia nigra and striatum in non-PD patients can affect behavioral and neuronal responses to algetic stimulation; the basal ganglia may be involved in the modulating of nociceptive information (including sensory-discriminative, cognitive, and affective aspects of noxious stimuli). This modulation most likely occurs within the medial thalamus. It is possible that the structures in the basal ganglia provide a gating mechanism for regulation of nociceptive stimuli to higher motor centers.8,9

The use of L-dopa or injections of apomorphine (Apokyn) may transiently help patients with PD experiencing CNP.

Spinal Cord Injury
Pain is a frequent phenomena after spinal cord injury (SCI) and is very difficult to treat. It may involve various aspects of the brain. These patients may experience central pain beginning within weeks or months after injury. It is typically felt at or below the level of SCI in areas where patients have lost some or all of their sensation.

There also may be segmental pain around the border where patients have normal sensation and loss of feeling secondary to the SCI. Segmental pain may be associated with allodynia and hyperalgesia in the painful region. If a patient also has nerve root entrapment and/or syringomyelia (a hollow fluid-filled cavity, or syrinx) in the spinal cord, which commonly expands, more neurological damage may also develop. Some research have demonstrated the development of central sensitization of dorsal horn neurons after spinal cord hemisection. This would provide a logical mechanism for the development of mechanical and thermal allodynia after SCI.10

Recent research takes this hypothesis further. Dendritic spine remodeling occurs on second-order wide dynamic range neurons and accompanies neuropathic pain after SCI, showing the possibility that a synaptic model of long-term memory storage could explain the persistent nature of neuropathic pain, as SCI-induced synaptic potentiation engages a putative spinal memory mechanism.11

However, other research demonstrates that chronic pain after SCI appears to be associated with nociceptive primary afferent neurons, which display persistent hyperexcitability and spontaneous activity in their peripheral branches and somata in dorsal root ganglia (DRG) after SCI, suggesting that SCI-induced alterations of primary nociceptors contribute to central sensitization and chronic pain after SCI.12

Gwak et al indicate the SCI-induced release of glutamate, proinflammatory cytokines, adenosine triphosphate (ATP), reactive oxygen species, and neurotrophic factors trigger activation of postsynaptic neuron and glial cells via their own receptors and channels that contribute to neuronal-neuronal- and neuronal-glial interaction as well as microglia-astrocytic interactions. Post SCI, dysfunctional glia, a condition they call “gliopathy,” is a key contributor to underlying cellular mechanisms contributing to neuropathic pain.13

Finnerup indicates that chronic pain is present in about 70% of patients with SCI and chronic CNP in 30% to 50%.14 She concluded that: 1) evoked types of pain are more common in SCI patients with central pain; 2) lesions in central gray matter are larger in SCI patients with central pain; and 3) spinothalamic tract lesions are equally common in SCI patients with and without central pain.

First published on: March 31, 2012