Definition and Overview
Neuropathic pain is defined by the IASP as pain caused by a lesion or disease of the somatosensory nervous system. It affects 7-10% of the general population and is characterized by burning, shooting, or electric shock-like sensations with allodynia and hyperalgesia [1].
Pathophysiology
Peripheral sensitization: damaged nerves develop ectopic discharge and upregulate sodium channels (Nav1.7, Nav1.8), lowering firing thresholds [2].
Central sensitization: spinal dorsal horn neurons become hyperexcitable through NMDA receptor activation, expanding receptive fields and amplifying pain signals.
Loss of inhibitory interneurons: reduced GABAergic and glycinergic inhibition in the spinal cord disinhibits pain pathways [3].
Symptoms
- Spontaneous pain: continuous burning, intermittent shooting/stabbing
- Allodynia: pain from normally non-painful stimuli (light touch, clothing contact)
- Hyperalgesia: exaggerated pain response to painful stimuli
- Paresthesias/dysesthesias: tingling, pins-and-needles, unpleasant sensations
- Numbness: paradoxical combination of sensory loss with pain ("anesthesia dolorosa")
Diagnosis
The DN4 questionnaire (4 questions on pain quality) and LANSS scale aid clinical screening [4]. Quantitative sensory testing (QST) objectively measures sensory thresholds. NCS/EMG identifies nerve damage. Skin biopsy quantifies intraepidermal nerve fiber density for small fiber neuropathy.
Treatment
First-line medications [5]:
- Gabapentinoids: pregabalin (150-600 mg/day), gabapentin (1200-3600 mg/day)
- SNRIs: duloxetine (60-120 mg/day), venlafaxine (150-225 mg/day)
- Tricyclic antidepressants: amitriptyline, nortriptyline (25-150 mg/day)
Second-line: tramadol, lidocaine 5% patch, capsaicin 8% patch. Third-line: strong opioids (with caution), botulinum toxin type A.
Combination therapy (e.g., gabapentinoid + SNRI) is often necessary. Neuromodulation options include spinal cord stimulation (SCS) and transcutaneous electrical nerve stimulation (TENS).