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Flashcards in Chapter 53 Central Pain States Deck (79):

Central pain

a term used to describe the pain associated
with a wide range of disorders of the central nervous system


The International Association for the Study of Pain (IASP) defines central pain as

pain initiated or caused by a primary lesion or dysfunction of the CNS.


disorders of central pain include

poststroke, spinal
cord injury (SCI), traumatic brain injury, and multiple sclerosis


The leading cause of central pain originating in the brain is




extrathalamic lesions. These pain-generating lesions extend from the first synapse of the
dorsal horn, or trigeminal nuclei, to the cerebral cortex.



The predominant etiology is vascular in origin, accounting for 90% of brain central pain (supratentorial 78% and infratentorial 12%). Extrathalamic sites are involved in 50% to 75% of cases


Chronic poststroke
pain more commonly occurs in the presence of

thalamic lesions


Central pain of spinal origin is predominantly the result of



Many central pain patients maintain their ability to

touch, vibration, and joint movements. This supports the belief that the central pain involves the
spinothalamic tract and its thalamocortical projections.


The highest prevalence of central pain is reported in cases of lesions in the

spinal cord, medulla, and ventroposterior part
of the thalamus.


spinal cord injury (SCI) pain is broadly divided into

nociceptive and neuropathic with subclassification into
second and third tiers based on the anatomic structures involved, site of pain, and etiology.


Nociceptive pain may be

musculoskeletal or visceral in nature. The former may be secondary to overuse of certain parts of the body to compensate for regions of paresis or result from secondary changes in bone or joints.


Neuropathic pain usually seen in areas of

sensory abnormalities


Neuropathic pain has been
subdivided on the basis of

region, into at-level (radicular or central), above-level, and below-level pain to indicate the
presumed site of the lesion responsible for pain generation.


Taxonomy of Spinal Cord Injury Pain

Nociceptive Musculoskeletal

Bone, joint, muscle trauma or
Mechanical instability
Muscle spasm
Secondary overuse syndromes


Taxonomy of Spinal Cord Injury Pain


Renal calculus, bowel
dysfunction, sphincter
dysfunction, etc.
Dysreflexic headache


Taxonomy of Spinal Cord Injury Pain

Neuropathic: Above level

Complex regional pain


Taxonomy of Spinal Cord Injury Pain

Neuropathic: At level

Nerve root compression
(including cauda equina)
Spinal cord trauma/ischemia
Dual level cord and root


Taxonomy of Spinal Cord Injury Pain

Neuropathic: Below level

Spinal cord trauma/ischemia


neuropathic pain definition outlined by the IASP was

“pain initiated or caused by a primary lesion or
dysfunction in the nervous system


Grading System for Neuropathic Pain

Criteria to be evaluated for each patient
1. Pain with a distinct neuroanatomically plausible distribution*
2. A history suggestive of a relevant lesion or disease affecting the
peripheral or central somatosensory system†
3. Demonstration of the distinct neuroanatomically plausible
distribution by at least one confirmatory test‡
4. Demonstration of the relevant lesion or disease by at least one
confirmatory test


Central pain states likely result from pathophysiologic
changes caused by

irritation of, or damage to, central pain pathways.


Injury to the CNS may result in

anatomic, neurochemical,
inflammatory, and excitotoxic changes that result in a sensitized
and hyperexcitable CNS


Several neurotransmitters are involved in the processing of
noxious input along the pain pathway

glutamate, gammaaminobutyric
acid (GABA), norepinephrine, serotonin, histamine,
and acetylcholine


The shift in firing
from a rhythmic burst to a single spike is determined by

noradrenergic, serotonergic, and cholinergic input to the
reticular and relay cells of the thalamus


excitatory amino acids, such as glutamate, are released in the region of
SCI and may lead to

neuronal hyperexcitability.


At the spinal cord level, substance P and cholecystokinin (CCK)
might play an additional role by

influencing the voltage gated sodium and calcium channels.


Potassium channels
play a critical role in

setting the resting membrane potential
and controlling the excitability of neurons


Central pain in SCI may result from

a combination of
deafferentation-induced plastic changes in supraspinal areas along with abnormal input from a pain generator in the spinal cord


In SCI, NMDA receptor activation might trigger

the intracellular cascade leading to the upregulation of neuronal activity/ excitability that results in spontaneous and evoked neuronal
hyperactivity/hyperexcitability and causes abnormal pain perception.


important mechanisms might be a loss of
endogenous inhibition, including

reduced GABA-ergic,
opioid, and monoaminergic inhibition.


Central glutamate

Central glutamate
levels are known to increase in response to pain in healthy humans, and patients with fibromyalgia are known to have elevated central glutamate levels that
directly correlate with response to painful stimuli


Patients with fibromyalgia are also known to have

dopamine and opioid receptor availability in
the forebrain.


Patients with complete SCI are known to have

a postinjury reorganization
of the somatosensory cortex that correlates with
pain intensity


Proposed mechanism of central
pain in spinal cord injury. Input from primary
afferents can be distorted by two mechanisms.


The spinothalamic tract projection neurons from
below the spinal injury may be lesioned and give rise to deafferentation hyperexcitability in higher-order neurons including the thalamus. Second-order neurons in the dorsal horn at the rostral end of the spinal lesion may become hyperexcitable as a
consequence of excitotoxic changes and
disinhibition from damaged GABA-ergic neurons at the level of injury. Abnormal input from these second-order neurons in the rostral end of the spinal cord lesion may propagate via the
propriospinal system to the deafferentated thalamic neurons resulting in pain referred to areas below injury level


explain why pain occurs more often in patients with partial lesions than in those with complete
cord and thalamic injuries.

Lesions in the spinothalamocortical pathways can cause ectopic discharges in various neurons of the spinal cord and brain. Such ectopic neuronal discharges create
an illusion of noxious input because of the imbalance
between the lateral (inhibitory) and medial (excitatory) STT


explain why pain occurs more often in patients with partial lesions than in those with complete
cord and thalamic injuries

It appears that severe CNS
lesions, with total destruction of ascending sensory systems, do not lead to a central pain syndrome and that
mild, moderate, or severe disruption of the anterolateral ascending system, with partial or complete preservation
of the dorsal column/medial lemniscus functions, is most
frequently associated with central pain syndrome


central pain frequently develops weeks or months
after development of the lesion and is associated with sensory changes involving the spinothalamic pathways, especially changes in temperature perception

Sensory stimuli act on neural systems that have been modified by previous inputs, the “memory” of which
significantly influences pain behavior. The fact that a memory is not activated by the development of a lesion
might explain the long delay in the onset of central pain in some patients. The long-term potentiation that is
important for this memory might be mediated by NMDA receptors and their influence on calcium conductance.



the macrophages of the
brain and spinal cord that release inflammatory mediators in the event of injury or infection. The activation of microglia and subsequent inflammation is thought to precipitate a cycle of further inflammation and activation of astrocytes.


neuropathic component of central pain quality of the pain may be

burning, aching, shooting,
pricking, and tingling. The discomfort is generally constant but may wax and wane and often has a deep and/or a superficial component.


can provoke or exacerbate spontaneous pain

Nonpainful tactile, thermal, vibratory,
auditory, visual, olfactory, and visceral stimuli


Patients with classic Dejerine-Roussy
syndrome have a

a rapidly regressing hemiparesis and a sensory deficit to touch, temperature, and pain. Allodynia, hyperalgesia, and spontaneous severe paroxysmal pain on
the hemiparetic side also often occur. These patients can exhibit hemiataxia, hemiastereognosia, and choreoathetoid movements.


Organic signs on sensory examination of patients
with thalamic lesions include

the so-called thalamic
midline split for sensory loss and pain.


Patients with a history of spontaneous or evoked dysesthesia,
hyperesthesia, or paresthesia should undergo

specific but simple bedside testing.


Sensory testing in the region where the pain is localized usually shows a

paradoxic hypoalgesia (decreased sensitivity to painful stimulus).
The region where the patient feels the pain often has decreased sensitivity to thermal stimuli, especially to cold.


Testing for disturbed
temperature sensation can be accomplished with

a cold metal instrument, ice, or ethyl chloride spray.


Touch can be tested with

cotton wool, while pinprick sensation should be assessed using the contralateral side as a control.


Chronic poststroke pain patients have an intact

vibration sensation


Chronic poststroke pain patients may exhibit mitempfindung (with sympathy)

a phenomenon in which stimulation in one area of the
body results in a simultaneous sense of the provoked sensation
in another part of the body


Chronic poststroke pain patients may exhibit alloesthesia

in which a sensory stimulus on one
side of the body is perceived on the other side


Testing for autonomic dysfunction may be important in
patients with SCI.

Lesions above the sixth thoracic level
(splanchnic outflow) are often associated with autonomic dysreflexia.


Dysreflexia characterized by

sudden dramatic increases in blood pressure, high or low heart rate, and headache after sensory input such as a full bladder.


Dysreflexia becomes especially important in SCI patients having surgery where

below the level of their lesion, including
minor operations of the urinary (i.e., cystoscopy)
or gastrointestinal (i.e., colonoscopy) systems where the viscera will be stimulated.


the goal of therapy is to

improve function and reduce pain without
creating intolerable side effects


options available for managing central
pain include

pharmacotherapy, behavioral therapy,
physical therapy, neuromodulation, other interventional
therapies, and ablative neurosurgery


The mainstay of central pain

antidepressants that possibly act by modulating the thalamic burst firing activity via its actions on locus coeruleus
noradrenergic neurons and the serotoninergic cells in the dorsal raphe


Amitriptyline is often effective in

central poststroke control and SCI pain. Amitriptyline’s benefit derives, in part, from its ability to prevent reuptake of noradrenaline
and serotonin.


Tricyclic antidepressants (TCAs) dose

should be titrated to 50 to 100 mg/day


a good regimen to control the common, steady, burning, dysesthetic component of this syndrome

a combination of a TCA (e.g., amitriptyline),
clonazepam, a benzodiazepine, and a (NSAID)


Antiepileptic drugs (AEDs) are useful for

the treatment of neuropathic pain. Currently, the most commonly prescribed
AEDs are gabapentin and pregabalin. Both gabapentin and pregabalin appear to be effective in treating
central pain



may benefit some patients; however, it is not first-line therapy. Patients who respond to a trial of opioid infusion may be prescribed long-acting opioids, such as the slow-release formulations or the transdermal preparation.


Central Pain Treatment Algorithm

Step 1. Identify problems.

Determine existing problems and potential adverse sequelae.
Identify biologic and psychological contributors to pain and their influence on the individual’s pain experience.
Determine the impact of pain on the patient’s function.
Determine how well the patient has adjusted to the disorder causing their central pain (SCI, stroke, MS).
Determine the risk of and/or presence of additional consequences of pain and the disorder underlying the central pain (i.e., pressure sores,
contractures, adverse drug effects).


Central Pain Treatment Algorithm

Step 2. Determine reasonable objectives/goals for patient and treating physician

Pain relief/reduction.
Treatment of spasm—decrease frequency and/or severity.
Increase exercise tolerance and improve function.
Achieve independent living.
Return to work


Central Pain Treatment Algorithm


First line :AEDs (gabapentin and pregabalin)
Second line: TCAs, SNRIs
Combinations with AED
Third line: Opioids, SSRI
Fourth line: Ketamine infusion, Lidocaine infusion


Central Pain Treatment Algorithm


Specific to condition
Limited evidence
Mainly for refractory cases
Spinal cord stimulation (SCS)> DBS, MCS deep brain or motor cortex
Intrathecal therapy
Baclofen, Morphine, Clonidine, Ziconotide
Ablative therapies (DREZ,


Central Pain Treatment Algorithm

Physical and Occupational Therapy

Structured therapy and home exercises
Postural re-education
Spasticity treatment
Bowel/bladder management
Braces and devices to assist in home and work
Home/work remodeling
Speech therapy


Central Pain Treatment Algorithm


Psychiatric therapy
Pain coping skills
Family support and


electrical nerve stimulation (TENS) provides

long-term benefits to patients with central poststroke pain and those with incomplete SCI


poor candidates for SCS

Patients with anesthesia dolorosa (pain in an anesthetic area) and patients with incomplete lesions are poor candidates. Patients who experience more than 50% pain relief during trial stimulation are potential candidates for an implant. In patients with treatment failure, deep brain stimulation (DBS) of the tactile relay nucleus of
the thalamus or the lemniscal radiations offers hope.


For brain-origin central pain

The neuralgic component is the component sometimes responsive to ablative neurosurgery. SCS is of no benefit for brain-origin central pain, although patients might report relief during a trial. Paresthesia producing DBS and motor cortex stimulation are appropriate
for the steady component of the pain.


The most commonly administered medications in Intrathecal pumps are

(morphine, hydromorphone, and fentanyl), clonidine, and



a GABA agonist, has antinociceptive effects,
and its intrathecal administration reduces allodynic responses
of neurogenic central pain


baclofen can be helpful in treating pain and spasticity
multiple types of central pain, including

post-stroke, SCI
and MS pain


Ablative surgery includes

cordotomy, cordectomy, and dorsal root entry zone (DREZ) lesioning.


The goal of cordotomy and cordectomy

interruption of STTs


Cordectomy, the simplest destructive procedure, can benefit patients

with complete lesions.
It is not acceptable to most patients because it obviates their hope for eventual restoration of spinal cord function.


Percutaneous/open cordotomy

achieves the same
results as cordectomy and is offered to patients with incomplete lesions, but carries the risk of aggravating bladder dysfunction and inducing ipsilateral limb paresis.


dorsal root entry zone (DREZ)

equally effective for the neuralgic and the
evoked elements of spinal-origin central pain. most useful for the relief of end-zone pain (pain starting at the level of injury and extending distally). Pain extending diffusely, often sacrally distributed, and remotely distributed pain, described as phantom or diffuse burning pain, do not
respond well to DREZ.


dorsal root entry zone (DREZ) side effects

Although the procedure preserves the hope for future spinal cord function and avoids risk of limb paresis, it can interfere with residual bladder
function and requires a laminectomy and considerable skill.

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