Chapter 53 Central Pain States Flashcards
KEY POINTS 1. Central pain states are common sequelae of SCI and stroke. 2. Pathophysiology of central pain is not understood. 3. Alterations in several neurotransmitters occur, including glutamate, GABA, norepinephrine. 4. Involvement of the spinothalamocortical pathway is strongly supported by animal models, but the precise pathway in humans is unknown. 5. The three components of central pain (steady dysesthetic, intermittent neuralgic, and evoked) must all be treated. In central pain o
Central pain
a term used to describe the pain associated
with a wide range of disorders of the central nervous system
(CNS).
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
(MS).
The leading cause of central pain originating in the brain is
stroke
Dejerine-Roussy
syndrome
extrathalamic lesions. These pain-generating lesions extend from the first synapse of the
dorsal horn, or trigeminal nuclei, to the cerebral cortex.
etiology
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
right-sided
thalamic lesions
Central pain of spinal origin is predominantly the result of
trauma
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 inflammation Mechanical instability Muscle spasm Secondary overuse syndromes
Taxonomy of Spinal Cord Injury Pain
Nociceptive
Visceral
Renal calculus, bowel
dysfunction, sphincter
dysfunction, etc.
Dysreflexic headache
Taxonomy of Spinal Cord Injury Pain
Neuropathic: Above level
Compressive
mononeuropathies
Complex regional pain
syndromes
Taxonomy of Spinal Cord Injury Pain
Neuropathic: At level
Nerve root compression (including cauda equina) Syringomyelia Spinal cord trauma/ischemia Dual level cord and root trauma
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
levels
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
decreased
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.
FIGURE 53-3
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.
Microglia
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
Opioids
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
Pharmacologic
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
Interventional
Specific to condition Limited evidence Mainly for refractory cases Neuromodulation Spinal cord stimulation (SCS)> DBS, MCS deep brain or motor cortex stimulation Intrathecal therapy Baclofen, Morphine, Clonidine, Ziconotide Acupuncture Ablative therapies (DREZ, cordotomy)
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 function Home/work remodeling Speech therapy
Central Pain Treatment Algorithm
Psychosocial
Psychiatric therapy Pharmacologic Counseling CBT Pain coping skills Relaxation Family support and education
Transcutaneous
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
opioids
(morphine, hydromorphone, and fentanyl), clonidine, and
bupivacaine
Baclofen
a GABA agonist, has antinociceptive effects,
and its intrathecal administration reduces allodynic responses
of neurogenic central pain
Intrathecal
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.
