What is neuropathy pain?

Neuropathic Pain: Definition, Mechanisms, and Management

Neuropathic pain is pain arising as a direct consequence of abnormalities in the somatosensory system, characterized by burning, electrical shock-like sensations, stabbing pain, and abnormal sensitivity to touch and temperature. 1

Definition and Characteristics

Neuropathic pain results from injury or dysfunction of the peripheral or central nervous system. It affects approximately 7-10% of the general population and presents with distinctive features:

• Common descriptors:

  • Burning pain
  • Electrical shock-type shooting pain
  • Stabbing or knife-like pain
  • Uncomfortable tingling (paresthesia)
  • Contact pain (allodynia) - pain from normally non-painful stimuli
  • Abnormal temperature sensations (feet feeling very hot or cold)

• Distinctive patterns:

  • Often worse at night, causing significant sleep disturbance
  • May follow a "glove-and-stocking" distribution (starting distally in extremities)
  • Can progress from feet upward and eventually affect upper limbs

Pathophysiology

Neuropathic pain develops through several key mechanisms:

1. Peripheral mechanisms:

   • Damage to sensory neurons causes abnormal firing patterns
   • Injured nerves become hyperexcitable and fire spontaneously
   • Nociceptors (pain receptors) become sensitized to stimuli

2. Central mechanisms:

   • Central sensitization occurs in the spinal cord and brain
   • Imbalance between excitatory and inhibitory signaling
   • Pathological activation of microglia (immune cells in the central nervous system)

Types of Neuropathic Pain

Diabetic Peripheral Neuropathy

• Present in up to 50% of diabetic patients with long disease duration
• Often presents as painful symptoms in distal extremities
• May be associated with sudden changes in glycemic control 1

Acute Neuropathic Pain

• Can follow rapid changes in glycemic control in diabetics
• May occur after treatment of diabetic ketoacidosis
• Usually resolves within a year 1

Neuropathic Corneal Pain

• Occurs in the cornea, the most richly innervated tissue in the body
• Can present as burning, stinging, or aching sensations
• May include photophobia (sensitivity to light) and wind hyperalgesia 1

Other Types

• Post-herpetic neuralgia (following shingles)
• HIV-associated neuropathy
• Chemotherapy-induced neuropathy
• Trauma-related neuropathy
• Complex regional pain syndrome 1

Diagnosis

Diagnosis requires identifying characteristic symptoms and signs:

• History: Focus on pain quality (burning, shooting, electric-like)
• Physical examination: Look for sensory abnormalities (allodynia, hyperalgesia)
• Diagnostic tests: May include:
  • Nerve conduction studies
  • Skin biopsy to assess small fiber density
  • Quantitative sensory testing
  • In corneal neuropathic pain: "anesthetic challenge test" to localize pain source 1

Management Approaches

First-line Pharmacological Treatments

1. Antidepressants:

   • Tricyclic antidepressants (TCAs) like amitriptyline, nortriptyline
   • Serotonin-norepinephrine reuptake inhibitors (SNRIs) like duloxetine

2. Anticonvulsants:

   • Gabapentin
   • Pregabalin

3. For neuropathic corneal pain:

   • Topical nerve regenerative therapies (autologous serum tears)
   • Oral neuromodulators (pregabalin, gabapentin, duloxetine, amitriptyline) 1

Second-line Treatments

1. Opioids:

   • Tramadol
   • Morphine
   • Oxycodone (controlled release)

2. For refractory cases:

   • Low-dose naltrexone
   • Periorbital nerve blocks (for corneal pain)
   • Electrical spinal cord stimulation

Important Clinical Considerations

• Neuropathic pain often coexists with anxiety and depression, affecting up to two-thirds of patients with severe pain 1
• Sleep disturbance affects >95% of patients with severe neuropathic pain 1
• Treatment requires adequate time to take effect (3-4 months at therapeutic dose) 1
• Medication selection should consider side effects and comorbidities

Common Pitfalls in Management

1. Inadequate duration of treatment: Neuromodulators require 3-4 months at therapeutic doses to show effect

2. Failure to address psychological aspects: Depression and anxiety frequently accompany neuropathic pain and require concurrent management

3. Misdiagnosis: Other conditions can masquerade as neuropathic pain (entrapments, fasciitis, claudication) 1

4. Overlooking sleep disturbance: Pain often worsens at night, creating a cycle of sleep deprivation that exacerbates pain perception

5. Monotherapy limitations: Combination therapy may be necessary for adequate pain control

Neuropathic pain represents a significant challenge in clinical practice due to its complex mechanisms and often inadequate response to conventional analgesics. A structured approach to diagnosis and treatment, with careful consideration of the specific type of neuropathic pain and its underlying mechanisms, offers the best chance for meaningful symptom relief and improved quality of life.