Treatment of Small Fibre Neuropathy and Associated Pain
First-line treatment for small fibre neuropathy (SFN) should be gabapentin or pregabalin, with duloxetine as an alternative when these medications are not tolerated or ineffective. 1
Diagnosis and Clinical Presentation
Small fibre neuropathy affects the thinly myelinated Aδ and unmyelinated C nerve fibres, which are involved in temperature and pain perception. The clinical presentation typically includes:
- Painful burning sensation in feet and/or hands
- Lancinating pain that can be potentiated by pin-prick testing
- Decreased pain perception and temperature sensation in affected areas
- Possible autonomic symptoms (postural hypotension, bladder disturbances, altered heart rate variability)
Pharmacological Treatment Options
First-Line Treatments
Gabapentin
- Starting dose: 100-300 mg daily
- Target dose: 900-3600 mg/day (divided into 3 doses)
- Requires dose adjustment in renal impairment 1
- Allow 2-4 weeks at target dose to assess efficacy
Pregabalin
- Starting dose: 50-75 mg twice daily
- Target dose: 300-600 mg/day (divided into 2-3 doses)
- Patients who don't experience sufficient pain relief after 2-4 weeks at 300 mg/day may increase to 600 mg/day 2
- Dose-dependent adverse reactions include dizziness, somnolence, peripheral edema, and weight gain
Second-Line Treatments
Duloxetine (SNRI)
- Starting dose: 30 mg daily
- Target dose: 60-120 mg/day
- Avoid in patients with hepatic impairment 1
- Particularly effective for chemotherapy-induced neuropathy
Tricyclic Antidepressants (TCAs)
- Amitriptyline 25-75 mg/day or imipramine 25-75 mg/day 3
- Nortriptyline preferred due to better side effect profile
- Starting dose: 10-25 mg at bedtime
- Target dose: 25-100 mg at bedtime
Third-Line Treatments
Tramadol
- Dose: 200-400 mg/day in 2-3 divided doses 1
- Consider when first and second-line treatments fail
Strong Opioids
- Use at smallest effective dose
- Reserve as salvage option when other treatments fail 1
- Risk of dependence and side effects limit long-term use
Topical Treatments
- Capsaicin 8% patch: Applied for 30-60 minutes, with effects lasting up to 90 days 1
- Topical menthol cream (1%): Applied twice daily to affected areas
- Topical baclofen/amitriptyline/ketamine gel: Particularly effective for motor symptoms
Treatment Algorithm
Initial Assessment
- Confirm diagnosis of small fibre neuropathy
- Identify and treat underlying causes (diabetes, autoimmune conditions, etc.)
- Optimize glycemic control if diabetes is present 3
First-Line Treatment
- Start with gabapentin or pregabalin
- Begin at low dose and titrate gradually
- Allow 2-4 weeks at target dose to assess efficacy
If Inadequate Response After 4 Weeks
- Switch from gabapentin to pregabalin (or vice versa)
- OR add duloxetine
- OR switch to a tricyclic antidepressant
For Refractory Cases
- Consider tramadol or strong opioids at lowest effective dose
- Add topical treatments such as capsaicin patch
- Consider referral to pain specialist
Non-Pharmacological Approaches
- Cognitive Behavioral Therapy
- Physical exercise
- Transcutaneous Electrical Nerve Stimulation (TENS)
- For SFN related to sarcoidosis, intravenous immunoglobulin (IVIg) or anti-TNF therapy may be considered, though evidence is limited 3
Important Considerations and Pitfalls
Regular assessment of efficacy and side effects is essential to optimize therapy
Early pain management is crucial, as chronic pain becomes more difficult to treat
Common pitfalls include:
- Inadequate dosing
- Premature discontinuation of treatment
- Fixation on monotherapy
- Overlooking non-pharmacological approaches
- Failure to address underlying causes
Dose adjustments are necessary for gabapentin and pregabalin in patients with renal impairment (creatinine clearance <60 ml/min) 1
By following this structured approach to the management of small fibre neuropathy, clinicians can optimize pain control and improve quality of life for affected patients.