Abstract
Abbreviations and Acronyms:
CHEP (contact heat–evoked potential), CNS (central nervous system), CPRS (complex regional pain syndrome), LEP (laser-evoked potential), NMDA (N-methyl-d-aspartate), NNT (number needed to treat), QSART (quantitative sudomotor axon reflex test), RCT (randomized controlled trial), SNRI (serotonin-norepinephrine reuptake inhibitor), TCA (tricyclic antidepressant)- 1.
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Pathology | Peripheral | Spinal | Brain |
---|---|---|---|
Genetic | Fabry neuropathy | Syringomyelia | Syringobulbia |
Metabolic | Painful diabetic neuropathy | B12 myelopathy | |
Traumatic | Nerve injury | Spinal cord injury | Multiple sclerosis |
Vascular | Vasculitic neuropathy | Spinal cord stroke | Brain stroke |
Neoplastic | Tumor compression neuropathy | Tumor compression | Tumor compression |
Immunological | Guillain-Barré syndrome | Multiple sclerosis | Multiple sclerosis |
Infectious | HIV, Borreliosis | Infectious myelitis | Encephalitis |
Toxic | Chemotherapy neuropathy |
Neuropathic Pain Mechanisms Relevant to Diagnosis and Treatment
Ectopic Activity
Peripheral Sensitization
Central Sensitization
Impaired Inhibitory Modulation
Activation of Microglia
Primary Care Approach to Neuropathic Pain Assessment
Signs and Symptoms Characteristic of Neuropathic Pain
Basic Sensory Examination
Quantitative Sensory Testing
Demant DT, Lund K, Vollert J, et al. The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified study [published online ahead of print August 17, 2014]. Pain. http://dx.doi.org/10.1016/j.pain.2014.08.014.
Demant DT, Lund K, Vollert J, et al. The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified study [published online ahead of print August 17, 2014]. Pain. http://dx.doi.org/10.1016/j.pain.2014.08.014.
Demant DT, Lund K, Vollert J, et al. The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified study [published online ahead of print August 17, 2014]. Pain. http://dx.doi.org/10.1016/j.pain.2014.08.014.
Other Special Tests
- Lauria G.
- Hsieh S.T.
- Johansson O.
- et al.
European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society.
Overview of Treatment Goals and Strategies in Neuropathic Pain
Drug Therapy for Neuropathic Pain
Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis [published online ahead of print January 6, 2015]. Lancet Neurol. http://dx.doi.org/10.1016/S1474-4422(14)70251-0.
Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis [published online ahead of print January 6, 2015]. Lancet Neurol. http://dx.doi.org/10.1016/S1474-4422(14)70251-0.
Drug | Total daily dose and dose regimen | Recommendations |
---|---|---|
Strong recommendations for use | ||
Gapabentin | 1200-3600 mg, in 3 divided doses | First line |
Gabapentin extended release or enacarbil | 1200-3600 mg, in 2 divided doses | First line |
Pregabalin | 300-600 mg, in 2 divided doses | First line |
Serotonin-norepinephrine reuptake inhibitors duloxetine or venlafaxine | 60-120 mg, once a day (duloxetine); 150-225 mg, once a day (venlafaxine extended release) | First line |
Tricyclic antidepressants | 25-150 mg, once a day or in 2 divided doses | First line
c
Tricyclic antidepressants generally have similar efficacy; tertiary amine tricyclic antidepressants (amitriptyline, imipramine, and clomipramine) are not recommended at doses >75 mg/d in adults aged 65 y and older because of major anticholinergic and sedative adverse effects and potential risk of falls32; an increased risk of sudden cardiac death has been reported with tricyclic antidepressants at doses >100 mg/d.33
|
Weak recommendations for use | ||
Capsaicin 8% patches | One to 4 patches to the painful area for 30-60 min every 3 mo | Second line (peripheral neuropathic pain) |
Lidocaine patches | One to 3 patches to the region of pain once a day for up to 12 h | Second line (peripheral neuropathic pain) |
Tramadol | 200-400 mg, in 2 (tramadol extended release) or 3 divided doses | Second line |
Botulinum toxin A (subcutaneously) | 50-200 units to the painful area every 3 mo | Third line; specialist use (peripheral neuropathic pain) |
Strong opioids | Individual titration | Third line |
Medication | Major adverse effects | Precautions | Contraindications | Comments and recommendations |
---|---|---|---|---|
TCAs | ||||
Nortriptyline and desipramine (amitriptyline, imipramine) | Cardiac conduction block, sedation, confusion, anticholinergic effects (dry mouth, constipation, urinary retention, blurred vision), orthotratic hypotension, weight gain | Use with caution in patients with history of seizures, prostatic hypertrophy, urinary retention, chronic constipation, narrow-angle glaucoma, increased intraocular pressure, or suicidal ideation; use with caution in patients receiving concomitant SSRI, SNRI, or tramadol treatment | Recovery phase after myocardial infarction, arrhythmias (particularly heart block of any degree), concomitant use of MAO inhibitors, porphyria | ECG screening recommended in adults older than 40 y; heart rate and blood pressure follow-up (both supine and standing measurements) recommended with dose escalation; ECG and blood concentration follow-up recommended at doses of >150 mg/d: follow-up of weight recommended, especially in diabetic patients |
SNRIs | ||||
Duloxetine | Nausea, loss of appetite, constipation, sedation, dry mouth, hyperhidrosis, anxiety | Use with caution in patients with history of mania, seizures, or bleeding tendency or those taking anticoagulants; use with caution in patients taking concomitant SSRI or tramadol treatment | Concomitant use of MAO inhibitors: uncontrolled hypertension | Blood pressure follow-up recommended in patients with known hypertension and/or other cardiac disease, especially during the first month of treatment. Smokers have almost 50% lower plasma concentrations of duloxetine than do nonsmokers |
Venlafaxine | Nausea, loss of appetite, hypertension, sedation, insomnia, anxiety, dry mouth, hyperhidrosis, constipation | Use with caution in patients with hypertension; use with caution in patients taking concomitant SSRI or tramadol treatment | Concomitant use of MAO inhibitors | Blood pressure follow-up recommended |
Gabapentinoids | ||||
Gabapentin | Sedation, dizziness, weight gain, edema, blurred vision | Simple antacids reduce bioavailability | Follow-up of weight recommended, especially in diabetic patients | |
Pregabalin | Sedation, dizziness, weight gain, edema, blurred vision | Follow-up of weight recommended, especially in diabetic patients |
Antidepressants
Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis [published online ahead of print January 6, 2015]. Lancet Neurol. http://dx.doi.org/10.1016/S1474-4422(14)70251-0.
Anticonvulsants
Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis [published online ahead of print January 6, 2015]. Lancet Neurol. http://dx.doi.org/10.1016/S1474-4422(14)70251-0.
Opioids
Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis [published online ahead of print January 6, 2015]. Lancet Neurol. http://dx.doi.org/10.1016/S1474-4422(14)70251-0.
Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis [published online ahead of print January 6, 2015]. Lancet Neurol. http://dx.doi.org/10.1016/S1474-4422(14)70251-0.
Interventional Management of Neuropathic Pain
Special Conditions
Central Pain
Complex regional pain syndrome
Trigeminal Neuralgia
Conclusion
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Article info
Footnotes
Grant Support: This work was supported in part by the Canadian Institutes of Health Research (grant no. MSH-55041 awarded to Dr Gilron).
Potential Competing Interests: Dr Jensen has received financial support from Pfizer, Grunenthal, Orion and Astellas as compensation for participating as consultant.
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