What is the treatment for diffuse neuropathic pain and burning sensation throughout the body?

Treatment for Diffuse Neuropathic Pain and Burning Sensation Throughout the Body

For diffuse neuropathic pain with burning sensation throughout the body, initiate treatment with pregabalin 75 mg twice daily, titrating to 150-300 mg twice daily (300-600 mg/day total) based on response and tolerability, as this is the first-line agent with the strongest evidence for widespread neuropathic pain. 1, 2

First-Line Pharmacological Treatment

Pregabalin (Preferred Agent)

• Start with 75 mg twice daily (150 mg/day total), increasing to 150 mg twice daily (300 mg/day) within 1 week based on efficacy and tolerability 1, 2
• For patients not experiencing sufficient relief at 300 mg/day who tolerate the medication well, increase to 300 mg twice daily (600 mg/day maximum) 1, 2
• Pregabalin has linear pharmacokinetics making dosing predictable, and demonstrates efficacy with NNT of 4.04 for 600 mg/day and 5.99 for 300 mg/day 1
• Common side effects include dizziness, somnolence, peripheral edema, headache, and weight gain 1

Alternative First-Line Agents if Pregabalin is Contraindicated

Gabapentin:

• Titrate up to 1800-3600 mg/day in divided doses (typically three times daily) 1, 3
• Less predictable dosing than pregabalin due to non-linear pharmacokinetics 1
• Similar side effect profile to pregabalin 1

Duloxetine (SNRI):

• Start at 30 mg daily, increase to 60 mg daily after 1 week 1
• Can increase to 120 mg/day if needed for additional benefit 1
• NNT of 4.9 for 120 mg/day and 5.2 for 60 mg/day 1
• Advantages include no weight gain and antidepressant effects 1
• Most frequent adverse effects: nausea, somnolence, dizziness, constipation, dry mouth (typically mild to moderate and transient) 1

Second-Line Treatment Options

Tricyclic Antidepressants

• Start with nortriptyline or desipramine 10-25 mg at bedtime, increasing every 3-5 days as tolerated 1, 4
• Target dose typically 75 mg/day, with caution not to exceed 100 mg/day due to increased risk of sudden cardiac death 1
• Obtain baseline ECG before initiating; avoid if PR or QTc interval is prolonged 1
• Use with extreme caution in patients with cardiovascular disease or elderly patients 1
• Side effects include drowsiness and anticholinergic effects (dry mouth, constipation, urinary retention, confusion) 1

Adjunctive and Topical Therapies

For Localized Areas of Severe Pain

High-concentration capsaicin 8% patch (Qutenza):

• Apply for 30-60 minutes under medical supervision to the most painful areas 5
• Mandatory pretreatment with topical lidocaine 4% for 60 minutes before application to reduce discomfort 5
• Provides pain relief lasting up to 12 weeks from a single application 5
• Approximately 31% of patients achieve >30% pain reduction compared to 14% with placebo 5
• Prescribe short-acting opioids or acetaminophen for use during and up to 7 days after application due to intense initial burning 5
• Can be reapplied every 90 days if pain returns 5

Lidocaine 5% patch:

• Apply to localized painful areas for up to 12 hours daily 1, 4
• Minimal systemic absorption, making it safe with minimal drug interactions 4

Treatment Algorithm

1. Initial Assessment:

   • Confirm neuropathic pain characteristics: burning quality, dysesthesia, allodynia (painful response to light touch), distribution pattern 1, 6
   • Identify underlying etiology (diabetes, HIV, chemotherapy, spinal cord injury, etc.) 1, 6
   • Assess for red flags: progressive symptoms suggesting malignancy, giant cell arteritis in patients >50 years 1

2. First-Line Treatment Selection:

   • Preferred: Pregabalin 75 mg twice daily, titrate weekly to 150-300 mg twice daily 1, 2
   • Alternative: Duloxetine 30-60 mg daily if comorbid depression or patient prefers to avoid weight gain 1
   • Alternative: Gabapentin 300 mg three times daily, titrate to 1800-3600 mg/day if pregabalin unavailable 1

3. Reassess at 2-4 Weeks:

   • If <30% pain reduction: increase dose to maximum tolerated (pregabalin up to 600 mg/day, duloxetine up to 120 mg/day) 1, 2
   • If inadequate response at maximum dose: add second agent from different class 1

4. Second-Line Add-On or Switch:

   • Add tricyclic antidepressant (nortriptyline 10-75 mg at bedtime) if first-line agent provides partial benefit 1
   • Consider switching to alternative first-line agent if no benefit or intolerable side effects 1

5. Adjunctive Topical Therapy:

   • For localized areas of severe pain: add capsaicin 8% patch with proper pretreatment protocol 5
   • For any localized component: add lidocaine 5% patch 1, 4

6. Refractory Pain (if <50% relief after trials of 2-3 agents):

   • Consider opioid therapy (tramadol or traditional opioids) as third-line option 1
   • Refer to pain specialist for consideration of interventional techniques (nerve blocks, intrathecal drug delivery) 1

Special Considerations and Common Pitfalls

Renal Impairment:

• Pregabalin and gabapentin require dose adjustment based on creatinine clearance 2
• For CrCl 30-60 mL/min: reduce pregabalin dose by 50%; for CrCl 15-30 mL/min: reduce by 75% 2
• Duloxetine is preferred in moderate renal impairment as it requires less adjustment 4

Cardiovascular Disease:

• Avoid tricyclic antidepressants or use with extreme caution and ECG monitoring 1
• Venlafaxine (another SNRI) should be avoided due to cardiovascular adverse events 1

Elderly Patients:

• Start tricyclic antidepressants at 10 mg/day due to increased anticholinergic sensitivity 1
• Monitor closely for falls risk with gabapentinoids due to dizziness and somnolence 1

Drug Interactions:

• Duloxetine and other SSRIs inhibit CYP2D6; avoid paroxetine and fluoxetine in patients on tamoxifen 1
• Prefer sertraline, citalopram, or escitalopram if SSRI needed with tamoxifen 1

Common Pitfall - Inadequate Dosing:

• Many clinicians underdose gabapentinoids; ensure titration to effective doses (pregabalin 300-600 mg/day, gabapentin 1800-3600 mg/day) 1, 3

Common Pitfall - Premature Discontinuation:

• Allow 2-4 weeks at therapeutic dose before declaring treatment failure 1, 3
• Educate patients about trial-and-error nature of neuropathic pain treatment to prevent discouragement 4

Common Pitfall - Capsaicin Application:

• Never skip lidocaine pretreatment for capsaicin 8% patch - this is the most critical step for tolerability 5
• Warn patients to avoid contact with eyes, mucous membranes, and genitalia 5
• Healthcare staff must wear gloves during entire application process 5

Pain Assessment and Monitoring

• Use validated pain scales (0-10 numerical rating scale) at each visit to guide dose adjustments 1, 4
• Assess functional impact: sleep quality, mood, activities of daily living 1, 6
• Monitor for adverse effects at each dose escalation 1, 2
• Consider pain response of ≥30% reduction as clinically meaningful, with ≥50% reduction as substantial benefit 1, 2