Pain Syndromes: Neuropathic Pain

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Neuropathic Pain
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Pain Pathophysiology

• Nociceptive pain
• Neuropathic pain

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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

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Mechanisms of Neuropathic Pain

• Noninflammatory states
• Inflammatory states

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Pathophysiology of Neuropathic Pain

• Ectopic activity in the peripheral pathways,
  including axons and DRG
• CNS mechanisms

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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

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Neuropathic Pain and SMP

• Some neuropathic pains are sustained, at least in
  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

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Nociceptive Pain
Neuropathic Pain
PNS peripheral nervous system
PNS
Peripheral sensitization

Healthy nociceptors
Abnormal nociceptors
CNS
CNS central nervous system
Central sensitization
Normal transmission
Central reorganization
Physiologic state
Pathologic state
Pappagallo M. 2001.
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Neuropathic Pain

• Diverse syndromes with uncertain classification
• Mononeuropathies and polyneuropathies
• CRPS
• Deafferentation syndromes, including central pain

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Painful Mononeuropathies and Polyneuropathies

• 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, Sjögrens syndrome
• Idiopathic distal small-fiber neuropathy

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Painful Mononeuropathies and Polyneuropathies

• Neuropathies due to toxins arsenic, thallium,
  alcohol, vincristine, cisplatinum,
  didioxynucleosides
• Amyloid polyneuropathy primary and familial
• Neuropathies with monoclonal proteins
• Vasculitic neuropathy
• Neuropathy associated with Guillain-Barré
  syndrome
• Neuropathy associated with Fabrys disease

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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

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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 touch-evoked
  pain, intermittent abnormal sensations,
  spontaneous burning and shooting pains

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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

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Neuropathic Pain Clinical Characteristics

• Burning, shooting, electrical-quality pain
• May be aching, throbbing, sharp
• Neuropathic sensations dysesthesias, paresthesias

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Neuropathic Sensations

• Paresthesias abnormal spontaneous,
  intermittent, painless
• Dysesthesias abnormal spontaneous or
  touch-evoked, unpleasant

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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
  mildly noxious (mechanical or thermal) stimulus
• Hyperpathia delayed and explosive pain response
  to a noxious stimulus

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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

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Secondary Hyperalgesia

• Present in the zone surrounding an injury
• Characterized by dynamic mechanical allodynia
  cold hyperalgesia
• Indicative of CNS sensitization

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Diagnostic Workup Lab Tests

• Complete blood cell count with differential,
  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,
  Sjögrens titers (SS-A, SS-B), antineutrophil
  cytoplasmic antibody

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Diagnostic Workup Lab Tests

• Cryoglobulins
• Antisulfatide antibody titers, anti-HU titers
• Heavy metals serum and urine screens
• Cerebrospinal fluid study for demyelinating
  diseases and meningeal carcinomatosis

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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

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Biopsies

• Nerve (eg, sural nerve) to diagnose vasculitis,
  amyloidosis, sarcoidosis, etc.
• Skin to evaluate density of unmyelinated fibers
  within dermis and epidermis

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Neuropathic Pain Management

• Pharmacotherapy
• Nonopioid
• Opioid
• Adjuvant analgesics
• Interventional
• Neural blockade (eg, sympathetic nerve blocks)
• Neurostimulatory techniques (eg, spinal cord
  stimulation)
• Intraspinal infusion

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Neuropathic PainPharmacologic Therapies

• Gabapentin, carbamazepine, lamotrigine, and newer
  AEDs
• Antidepressants
• Opioid analgesics
• Lidocaine (transdermal, intravenous IV),
  mexiletine
• Alpha-2 adrenergic agonists

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Neuropathic Pain Management

• Rehabilitative approaches
• Psychologic interventions

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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

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