What are the treatment options for allodynia?

Treatment for Allodynia

For allodynia associated with neuropathic pain, initiate treatment with either gabapentin (starting 300 mg three times daily, titrating to 900-3600 mg/day) or pregabalin (starting 75-150 mg/day, titrating to 300-600 mg/day), as these agents specifically block both static and dynamic components of mechanical allodynia. 1, 2

First-Line Pharmacological Options

Calcium Channel α2-δ Ligands (Preferred for Allodynia)

• Pregabalin is the optimal first choice due to linear pharmacokinetics and faster titration 1

  • Start at 75-150 mg/day in 2-3 divided doses 1
  • Increase to 300 mg/day after 1-2 weeks 1
  • Maximum dose 600 mg/day (though 300 mg/day often sufficient) 1
  • Provides analgesia more quickly than gabapentin 1
  • Specifically effective for allodynia in postherpetic neuralgia and peripheral neuropathy 1

• Gabapentin as alternative if pregabalin unavailable 1

  • Start 100-300 mg at bedtime in elderly or renally impaired patients 1
  • Standard starting: 300 mg three times daily 1
  • Titrate to 900-3600 mg/day in divided doses 1
  • Requires 2 months for adequate trial 1
  • Superior antiallodynic profile compared to opioids and antidepressants 2

• Common side effects: dizziness, somnolence, peripheral edema, weight gain 1, 3

• Mechanism: Both agents block voltage-gated calcium channels, inhibiting glutamate, norepinephrine, and substance P release 1

• Evidence: Gabapentin produced 66% decreased pain and allodynia versus 33% with placebo in randomized trials 1

Topical Lidocaine (For Localized Allodynia)

• 5% lidocaine patch is highly effective for localized peripheral neuropathic pain with allodynia 1

  • Apply up to 3 patches for maximum 12 hours daily 1
  • Particularly advantageous in elderly due to lack of systemic effects 1
  • Proven efficacy in postherpetic neuralgia with allodynia 1
  • Most appropriate for well-localized peripheral neuropathic pain 1

• 5% lidocaine gel is less expensive alternative with similar efficacy 1

• Contraindication: Unlikely to benefit central neuropathic pain 1

Tricyclic Antidepressants (Alternative First-Line)

• Nortriptyline or desipramine preferred over amitriptyline due to fewer anticholinergic effects 1

  • Start 10 mg/day, especially in elderly 1
  • Titrate to 75 mg/day maximum 1
  • Avoid doses >100 mg/day due to cardiac risk 1
  • Obtain baseline ECG in patients >40 years 1

• Limitation: Morphine and amitriptyline block static but NOT dynamic allodynia 2

• Mechanism: Inhibit norepinephrine/serotonin reuptake and antagonize NMDA receptors 1

SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)

• Duloxetine 60-120 mg/day 1

  • FDA-approved for painful diabetic neuropathy 1
  • Start 30 mg/day, increase weekly 1
  • NNT 4.9-5.2 for 50% pain reduction 1

• Venlafaxine 150-225 mg/day 1

  • Effective but cardiovascular side effects limit use 1

Second-Line Options (When First-Line Inadequate)

Tramadol

• Dosing: Start 50 mg once or twice daily, increase to maximum 400 mg/day 1
• Indication: Acute neuropathic pain, episodic severe exacerbations, or when rapid relief needed during first-line titration 1
• Advantage: Lower abuse potential than opioids 1
• Caution: Lowers seizure threshold; risk of serotonin syndrome with SSRIs/SNRIs 1

Opioid Analgesics

• Morphine, oxycodone: Start morphine equivalent 10-15 mg every 4 hours 1
• Evidence: Morphine less potent for allodynia than for other neuropathic pain types 4
• Limitation: Does NOT effectively treat dynamic allodynia 2
• Reserve for: Cancer-related neuropathic pain, acute neuropathic pain, or failed first-line therapy 1

Third-Line and Adjunctive Treatments

High-Concentration Capsaicin

• 8% capsaicin patch for localized peripheral neuropathic pain with allodynia 1
• Single application provides 8-12 weeks of relief 1
• Requires pretreatment with topical anesthetic 1

Botulinum Toxin Type A

• Intradermal injection into area of mechanical allodynia 1
• Significantly reduced brush-evoked allodynia at 4 and 12 weeks in controlled trials 1
• Consider for refractory cases 3

Combination Therapy

• Morphine + pregabalin produces synergistic effect on mechanical allodynia 4
• Morphine + duloxetine synergistic for allodynia 4
• Pregabalin + duloxetine synergistic for allodynia 4
• Consider when monotherapy provides <50% pain reduction 1

Treatment Algorithm

1. Initiate pregabalin 75-150 mg/day OR gabapentin 300 mg three times daily 1

   • Add topical lidocaine 5% patch if allodynia is localized 1
   • Titrate over 2-4 weeks to therapeutic dose 1

2. If inadequate response after 4-8 weeks at therapeutic dose 1

   • Switch to duloxetine 60 mg/day OR nortriptyline 10-75 mg/day 1
   • OR add second first-line agent as combination therapy 1

3. If still inadequate after trials of 2 first-line agents 1

   • Add tramadol 50-400 mg/day 1
   • OR consider opioid analgesic with careful monitoring 1

4. For refractory cases 1, 3

   • High-concentration capsaicin patch 1
   • Botulinum toxin A injections 1
   • Referral to pain specialist 1

Critical Considerations

• Gabapentin and pregabalin are superior to morphine and amitriptyline because they block BOTH static and dynamic allodynia, while opioids and TCAs only address static allodynia 2
• Adequate trial duration: 4-6 weeks for gabapentinoids at therapeutic dose; 6-8 weeks for TCAs 1
• Dose adjustments: Lower starting doses and slower titration required in elderly and renally impaired patients 1
• Topical treatments: Preferred in elderly due to lack of systemic side effects and drug interactions 1
• Central vs peripheral: Topical lidocaine ineffective for central neuropathic pain; systemic agents required 1
• Expected outcomes: Average pain reduction 20-30%; only 20-35% achieve ≥50% pain reduction with monotherapy 3