Neuropathic Pain

BASICS

Definition: Injury to nociceptive pathways in the CNS or PNS, causing impairment, absence, or augmentation of pain sensation.
Typical symptoms: Burning, tingling, sharp, stabbing, shooting, electric shock-like pain.
Often severe and resistant to standard pain treatments.

Mechanisms: Damaged afferents/nociceptors become hypersensitive or fire spontaneously (upregulation of sodium channels).
Genetics: High expression of Nav1.7 (SCN9A) and Nav1.8 (SCN10A) channels on peripheral nociceptors.

Demographics: Older age, female sex, inactivity, manual work.
Diseases: Diabetes (type 1 & 2), MS, Guillain-Barré, herpes zoster, trigeminal neuralgia, HIV, Lyme disease, malignancy/chemo.
Medications: Isoniazid, ethambutol, chloroquine, paclitaxel, cisplatin, amiodarone, vincristine.
Nutritional: B6, B12 deficiencies.

Depression/anxiety, sleep disturbance, substance abuse, impaired cognition, polypharmacy, suicidality

Symptom onset, duration, location, intensity, triggers
Character: burning, shooting, tingling, electric
Sensory changes: numbness, weakness, reduced sensation, altered proprioception
Functional impact: sleep, self-care, sexual function
Prior treatments: resistance to acetaminophen/NSAIDs
Screening tools: Leeds Assessment, DN4, PainDETECT, Neuropathic Pain Symptom Inventory

Positive: Hyperalgesia (↑ pain to stimulus), allodynia (pain to light touch)
Negative: Hypoesthesia (↓ sensation to touch/temp)
Motor: Weakness, spasm, decreased ROM, tremor, dystonia, (hypo/hyper)reflexia
Sensory: Touch, pinprick, vibration, proprioception
Skin: Temp, color, sweating, hair (suggests sympathetic involvement/CRPS)
Other: Dermatomal scars (zoster), acanthosis nigricans (diabetes)

Confirmatory: (if needed)
Sensory assessment, QST, blink reflex, NCS/EMG, SSEP, LEP, skin biopsy, corneal microscopy, CT/MRI
Rule out secondary causes: B12, TSH, syphilis, fasting glucose/A1c, CBC, CMP, Lyme, HIV

Multimodal therapy; physical/occupational therapy for function
Limited efficacy: Most patients only partially benefit; combined therapy often best

Not effective: Acetaminophen/NSAIDs (may help in acute pain)
First Line:
Gabapentin: up to 3600 mg/day (renal adjust); sedation, dizziness, edema, weight gain
Pregabalin: up to 600 mg/day (renal adjust); same S/E
TCAs (amitriptyline, nortriptyline, etc): start 10–25 mg qHS, titrate to max 150 mg/day (limit <75 mg in elderly); anticholinergic, weight gain, cardiac conduction block, suicidality warning
SNRIs (duloxetine, venlafaxine): duloxetine 20–120 mg/day, venlafaxine 150–225 mg/day; nausea, HTN (venlafaxine), safest option
Second Line:
Lidocaine 5% patches: up to 3 patches for 12h/day; local irritation
Capsaicin 8% patch: 30–60 min application, lasts up to 3 months; pain, erythema
Third Line:
Botulinum toxin A: s.c. 50–200 U q3mo; pain, site infection/weakness
Cannabinoids (dronabinol, nabilone): low-quality evidence, adverse effects common
Opioids/tramadol: not recommended for long-term use, hyperalgesia risk, dependency

Pain clinic referral: For refractory cases, trial of additional therapies
Interventional: Nerve/epidural injection (40–60% partial, lasting relief), SCS (best for failed back surgery syndrome), intrathecal ziconotide
TENS: Slight benefit
CBT/mindfulness: Effective as adjunct, esp. postherpetic neuralgia

Nerve destruction rarely indicated (exceptions: terminal cancer); can cause more damage

Prognosis: Chronic course, usually needs ongoing multimodal management; complete relief rare
Complications: Long-term disability, drug addiction