Download Pain Syndromes: Neuropathic Pain

Neuropathic Pain
Pain Pathophysiology
• Nociceptive pain
• Neuropathic pain
Nociceptive Pain
• Sensitization and activation of “healthy”
nociceptor endings and recruitment of
“silent” nociceptors
• “Soup” of inflammatory algogenic agents,
such as protons, prostaglandins,
bradykinin, serotonin, adenosine,
histamine, cytokines
Mechanisms of Neuropathic Pain
• Noninflammatory states
• Inflammatory states
Pathophysiology of Neuropathic Pain
• Ectopic activity in the peripheral pathways,
including axons and DRG
• CNS mechanisms
Neuropathic Pain: Central Mechanisms
Peripheral neuropathic events can be
complicated by temporary or long-term
CNS changes, such as central sensitization
and then reorganization of the pain
pathways at the dorsal horn level
Neuropathic Pain and SMP
• Some neuropathic pains are sustained, at least in
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part, by sympathetic efferent activity
– SMP
Expression of alpha-adrenergic receptors on
injured C-fibers may be a relevant mechanism of
SMP, but others are possible
Clinical findings consistent with CRPS signal an
increased likelihood of SMP
Nociceptive Pain
Neuropathic Pain
PNS
peripheral
nervous
system
CNS
central
nervous
system
Peripheral
sensitization
“Healthy”
Abnormal
nociceptors
nociceptors
PNS
Central
CNS
Normal
transmission sensitization
Central
reorganization
Physiologic
state
Pappagallo M. 2001.
Pathologic
state
Neuropathic Pain
• Diverse syndromes with uncertain
classification
• Mononeuropathies and polyneuropathies
• CRPS
• Deafferentation syndromes, including
central pain
Painful Mononeuropathies and
Polyneuropathies
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Diabetic neuropathies
Entrapment neuropathies
Shingles and postherpetic neuralgia
Trigeminal and other CNS neuralgias
HIV-related neuropathy
Neuropathy due to malignant disease
Neuropathy due to rheumatoid arthritis, systemic
lupus erythematosus, Sjögren’s syndrome
Idiopathic distal small-fiber neuropathy
Painful Mononeuropathies and
Polyneuropathies
• Neuropathies due to toxins: arsenic, thallium,
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alcohol, vincristine, cisplatinum,
didioxynucleosides
Amyloid polyneuropathy: primary and familial
Neuropathies with monoclonal proteins
Vasculitic neuropathy
Neuropathy associated with Guillain-Barré
syndrome
Neuropathy associated with Fabry’s disease
Neuropathic Pain: Clinical Assessment
• A comprehensive diagnostic approach to
patients affected by neuropathic pain
– Medical history
– Examinations: general, neurologic, regional
– Diagnostic workup: imaging studies,
laboratory tests, nerve/skin biopsies,
electromyography/nerve-conduction velocity
(EMG-NCV) studies, selected nerve blocks
Medical History
Ask patient about complaints suggestive of
• Neurologic deficits: persistent numbness
in a body area or limb-weakness, for
example, tripping episodes, inability to
open jars
• Neurologic sensory dysfunction: touchevoked pain, intermittent abnormal
sensations, spontaneous burning and
shooting pains
Neurologic and Regional Examinations
In patients with neuropathic pain,
examination should focus on the anatomic
pattern and localization of the abnormal
sensory symptoms and neurologic deficits
Neuropathic Pain: Clinical Characteristics
• Burning, shooting, electrical-quality pain
• May be aching, throbbing, sharp
• Neuropathic sensations: dysesthesias,
paresthesias
Neuropathic Sensations
• Paresthesias: abnormal; spontaneous,
intermittent, painless
• Dysesthesias: abnormal; spontaneous or
touch-evoked, unpleasant
Neuropathic Pain: Evoked Dysesthesias
• Allodynia: pain elicited by a nonnoxious stimulus
(clothing, air movement, touch)
– Mechanical (induced by light pressure)
– Thermal (induced by a nonpainful cold or warm
stimulus)
• Hyperalgesia: exaggerated pain response to a
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mildly noxious (mechanical or thermal) stimulus
Hyperpathia: delayed and explosive pain
response to a noxious stimulus
Primary Hyperalgesia
• Present in the primary zone, at the location
of injury
• Characterized by pinprick hyperalgesia +
warm and heat hyperalgesia + static
mechanical allodynia (tenderness)
• Indicative of PNS sensitization
Secondary Hyperalgesia
• Present in the zone surrounding an injury
• Characterized by dynamic mechanical
allodynia + cold hyperalgesia
• Indicative of CNS sensitization
Diagnostic Workup: Lab Tests
• Complete blood cell count with differential,
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erythrocyte sedimentation rate, chemistry profile
Thyroid-function tests, vitamin B12 and folate,
fasting blood sugar, and glycosylated hemoglobin
Serum protein electrophoresis with immunofixation
Lyme titers, hepatitis B and C, HIV screening
Antinuclear antibodies, rheumatoid factor,
Sjögren’s titers (SS-A, SS-B), antineutrophil
cytoplasmic antibody
Diagnostic Workup: Lab Tests
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Cryoglobulins
Antisulfatide antibody titers, anti-HU titers
Heavy metals serum and urine screens
Cerebrospinal fluid study for demyelinating
diseases and meningeal carcinomatosis
Diagnostic Workup: Electrophysiologic
Studies
EMG-NCV and QST
• To localize pain-generator/nerve or root
lesion
• To rule out
– Axonal vs focal segmental demyelination
– Underlying small-fiber or mixed
polyneuropathy
Biopsies
• Nerve (eg, sural nerve): to diagnose
vasculitis, amyloidosis, sarcoidosis, etc.
• Skin: to evaluate density of unmyelinated
fibers within dermis and epidermis
Neuropathic Pain: Management
• Pharmacotherapy
– Nonopioid
– Opioid
– Adjuvant analgesics
• Interventional
– Neural blockade (eg, sympathetic nerve blocks)
– Neurostimulatory techniques (eg, spinal cord
stimulation)
– Intraspinal infusion
Neuropathic Pain:
Pharmacologic Therapies
• Gabapentin, carbamazepine, lamotrigine,
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and newer AEDs
Antidepressants
Opioid analgesics
Lidocaine (transdermal, intravenous [IV]),
mexiletine
Alpha-2 adrenergic agonists
Neuropathic Pain: Management
• Rehabilitative approaches
• Psychologic interventions
Conclusions
• More effective medical therapies for
neuropathic pain are becoming available
and physicians should use them to limit
unnecessary suffering, with the ultimate
goal of significantly improving patients’
quality of life