Algorithm for neuropathic pain treatment: An evidence based proposal

New studies of the treatment of neuropathic pain have increased the need for an updated review of randomized, double-blind, placebocontrolled trials to support an evidence based algorithm to treat neuropathic pain conditions. Available studies were identified using a MEDLINE and EMBASE search. One hundred and five studies were included. Numbers needed to treat (NNT) and numbers needed to harm (NNH) were used to compare efficacy and safety of the treatments in different neuropathic pain syndromes. The quality of each trial was assessed. Tricyclic antidepressants and the anticonvulsants gabapentin and pregabalin were the most frequently studied drug classes. In peripheral neuropathic pain, the lowest NNT was for tricyclic antidepressants, followed by opioids and the anticonvulsants gabapentin and pregabalin. For central neuropathic pain there is limited data. NNT and NNH are currently the best way to assess relative efficacy and safety, but the need for dichotomous data, which may have to be estimated retrospectively for old trials, and the methodological complexity of pooling data from small cross-over and large parallel group trials, remain as limitations. q 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

[1]  Lars Arendt-Nielsen,et al.  Postoperative Hyperalgesia: Its Clinical Importance and Relevance , 2006, Anesthesiology.

[2]  M. Luu Gabapentin for neuropathic cancer pain: a randomized controlled trial from the gabapentin cancer pain study group , 2005 .

[3]  P. Hansson,et al.  Pharmacological treatment of peripheral neuropathic pain conditions based on shared commonalities despite multiple etiologies , 2005, Pain.

[4]  Smriti Iyengar,et al.  A double-blind, randomized multicenter trial comparing duloxetine with placebo in the management of diabetic peripheral neuropathic pain. , 2005, Pain medicine.

[5]  V. Wright,et al.  Sciatica and the intervertebral disc; an experimental study. , 1958, The Journal of bone and joint surgery. American volume.

[6]  P. Raskin,et al.  Double‐blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy , 1998, Neurology.

[7]  M. Versavel,et al.  Efficacy and tolerability of twice-daily pregabalin for treating pain and related sleep interference in postherpetic neuralgia: a 13‐week, randomized trial , 2006, Current medical research and opinion.

[8]  S. Kochar,et al.  Sodium valproate for painful diabetic neuropathy: a randomized double-blind placebo-controlled study. , 2004, QJM : monthly journal of the Association of Physicians.

[9]  D. Moulin,et al.  Use of opioid analgesics for the treatment of chronic noncancer pain--a consensus statement and guidelines from the Canadian Pain Society, 2002. , 2003, Pain research & management.

[10]  D. Blum,et al.  D. treatment approach (medical/interventional)D02 - anticonvulsant(726): Double-blind, placebo-controlled trial of add-on lamotrigine in patients with neuropathic pain and inadequate relief with gabapentin, TCAs or non-narcotic analgesics , 2006 .

[11]  J. Morley,et al.  Low-dose methadone has an analgesic effect in neuropathic pain: a double-blind randomized controlled crossover trial , 2003, Palliative medicine.

[12]  M. Fava,et al.  Clinical consequences of initial duloxetine dosing strategies: Comparison of 30 and 60 mg QD starting doses. , 2005, Current therapeutic research, clinical and experimental.

[13]  J. Kellgren,et al.  Referred Pains from Muscle* , 1938, British medical journal.

[14]  M. Rowbotham,et al.  Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia , 1991, Neurology.

[15]  D. Sackett,et al.  The number needed to treat: a clinically useful measure of treatment effect , 1995, BMJ.

[16]  J. Benneyan,et al.  Foundations of Opioid Risk Management , 2007, The Clinical journal of pain.

[17]  V. Mooney,et al.  The facet syndrome. , 1976, Clinical orthopaedics and related research.

[18]  D. Kochar,et al.  Sodium valproate in the management of painful neuropathy in type 2 diabetes - a randomized placebo controlled study. , 2003, Acta neurologica Scandinavica.

[19]  A R Jadad,et al.  Assessing the quality of reports of randomized clinical trials: is blinding necessary? , 1996, Controlled clinical trials.

[20]  D. Bouhassira,et al.  Effects of IV morphine in central pain: A randomized placebo-controlled study , 2002, Neurology.

[21]  K. Schmader Epidemiology and Impact on Quality of Life of Postherpetic Neuralgia and Painful Diabetic Neuropathy , 2002, The Clinical journal of pain.

[22]  D. DeWalt,et al.  Predictors of opioid misuse in patients with chronic pain: a prospective cohort study , 2006, BMC Health Services Research.

[23]  D. Carroll,et al.  Epidemiology and treatment of neuropathic pain: The UK primary care perspective , 2006, PAIN.

[24]  S. Dogra,et al.  Oxcarbazepine in painful diabetic neuropathy: a randomized, placebo‐controlled study , 2005, European journal of pain.

[25]  R. Moore,et al.  An Evidence-Based Resource for Pain Relief , 1998 .

[26]  M. Max,et al.  High‐dose oral dextromethorphan versus placebo in painful diabetic neuropathy and postherpetic neuralgia , 1997, Neurology.

[27]  E. Kalso,et al.  Venlafaxine in neuropathic pain following treatment of breast cancer , 2002, European journal of pain.

[28]  M. Max,et al.  Morphine, nortriptyline and their combination vs. placebo in patients with chronic lumbar root pain , 2007, PAIN.

[29]  G. Wiberg,et al.  Back pain in relation to the nerve supply of the intervertebral disc. , 1949, Acta orthopaedica Scandinavica.

[30]  A. Muñoz,et al.  Rates of abuse of tramadol remain unchanged with the introduction of new branded and generic products: results of an abuse monitoring system, 1994–2004 , 2005, Pharmacoepidemiology and drug safety.

[31]  T. Jensen,et al.  Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action , 1999, PAIN®.

[32]  J. Højsted,et al.  Addiction to opioids in chronic pain patients: A literature review , 2007, European journal of pain.

[33]  S. Leckband,et al.  Randomized double-blind study comparing the efficacy of gabapentin with amitriptyline on diabetic peripheral neuropathy pain. , 1999, Archives of internal medicine.

[34]  R. Vallejo,et al.  Opioid Therapy and Immunosuppression: A Review , 2004, American journal of therapeutics.

[35]  T. Nurmikko,et al.  Analgesic Therapy in Postherpetic Neuralgia: A Quantitative Systematic Review , 2005, PLoS medicine.

[36]  Tramadol for neuropathic pain. , 2006, The Cochrane database of systematic reviews.

[37]  J. Rull,et al.  Symptomatic treatment of peripheral diabetic neuropathy with carbamazepine (Tegretol®): Double blind crossover trial , 1969, Diabetologia.

[38]  G. Fromm,et al.  Carbamazepine in the treatment of neuralgia. Use of side effects. , 1968, Archives of neurology.

[39]  D. Clifford,et al.  Lamotrigine for HIV-associated painful sensory neuropathies , 2003, Neurology.

[40]  L. Gram,et al.  Adverse effects of established and new antiepileptic drugs: an attempted comparison. , 1995, Pharmacology & therapeutics.

[41]  D. Bowsher The lifetime occurrence of Herpes zoster and prevalence of post‐herpetic neuralgia: A retrospective survey in an elderly population , 1999, European journal of pain.

[42]  G. Y. Wong,et al.  A phase III double blinded, placebo controlled, randomized trial of gabapentin in patients with chemotherapy-induced peripheral neuropathy: A North Central Cancer Treatment Group study , 2005 .

[43]  H. Arnqvist,et al.  A comparison a amitriptyline and maprotiline in the treatment of painful polyneuropathy in diabetics and nondiabetics. , 1997, The Clinical journal of pain.

[44]  S D Kuslich,et al.  The tissue origin of low back pain and sciatica: a report of pain response to tissue stimulation during operations on the lumbar spine using local anesthesia. , 1991, The Orthopedic clinics of North America.

[45]  C D Naylor,et al.  Incorporating variations in the quality of individual randomized trials into meta-analysis. , 1992, Journal of clinical epidemiology.

[46]  M. Rowbotham,et al.  Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study , 2004, Pain.

[47]  R. Tandan,et al.  Topical Capsaicin in Painful Diabetic Neuropathy: Controlled Study With Long-Term Follow-Up , 1992, Diabetes Care.

[48]  J. Kellgren On the distribution of pain arising from deep somatic structures with charts of segmental pain areas , 1939 .

[49]  R. Deyo,et al.  Descriptive Epidemiology of Low‐back Pain and Its Related Medical Care in the United States , 1987, Spine.

[50]  R. Dubner,et al.  Amitriptyline relieves diabetic neuropathy pain in patients with normal or depressed mood , 1987, Neurology.

[51]  G. McCleane,et al.  Topical application of doxepin hydrochloride, capsaicin and a combination of both produces analgesia in chronic human neuropathic pain: a randomized, double-blind, placebo-controlled study. , 2000, British journal of clinical pharmacology.

[52]  M. Maschke,et al.  A placebo-controlled trial of gabapentin for painful HIV-associated sensory neuropathies , 2004, Journal of Neurology.

[53]  S. Lawrie,et al.  Cannabis as a risk factor for psychosis: systematic review , 2005, Journal of psychopharmacology.

[54]  M. Thase,et al.  Cardiovascular Profile of Duloxetine, a Dual Reuptake Inhibitor of Serotonin and Norepinephrine , 2005, Journal of clinical psychopharmacology.

[55]  A. Gordon,et al.  Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy , 2003, Pain.

[56]  H. Daniell Hypogonadism in men consuming sustained-action oral opioids. , 2002, The journal of pain : official journal of the American Pain Society.

[57]  A. Rice,et al.  Gabapentin in postherpetic neuralgia: a randomised, double blind, placebo controlled study , 2001, PAIN.

[58]  T. Jensen,et al.  Venlafaxine versus imipramine in painful polyneuropathy , 2003, Neurology.

[59]  G. Andersson,et al.  ▪ Consensus Summary on the Diagnosis and Treatment of Lumbar Disc Herniation , 1996, Spine.

[60]  H. Beck-Nielsen,et al.  Lack of effect of mianserin on the symptoms of diabetic neuropathy , 2006, European Journal of Clinical Pharmacology.

[61]  C. Nicol A FOUR YEAR DOUBLE‐BLIND STUDY OF TEGRETOL(r)IN FACIAL PAIN , 1969, Headache.

[62]  M. Wallace,et al.  Efficacy of Oral Mexiletine for Neuropathic Pain With Allodynia: A Double-Blind, Placebo-Controlled, Crossover Study , 2000, Regional Anesthesia & Pain Medicine.

[63]  D. Bickers,et al.  Topical capsaicin treatment of chronic postherpetic neuralgia. , 1989, Journal of the American Academy of Dermatology.

[64]  Niels Birbaumer,et al.  The effect of opioids on phantom limb pain and cortical reorganization , 2001, Pain.

[65]  G. Leijon,et al.  Central post-stroke pain — a controlled trial of amitriptyline and carbamazepine , 1989, Pain.

[66]  H. Merskey,et al.  Amitriptyline versus placebo in post-herpetic neuralgia , 1981, Pain.

[67]  J. Lau,et al.  Systemic administration of local anesthetic agents to relieve neuropathic pain. , 2005, The Cochrane database of systematic reviews.

[68]  M. Karst,et al.  Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial. , 2003, JAMA.

[69]  R. Poole,et al.  Pregabalin for the treatment of postherpetic neuralgia , 2003, Neurology.

[70]  A. Basbaum,et al.  Emerging Strategies for the Treatment of Neuropathic Pain , 2006 .

[71]  T. Jensen,et al.  Valproic acid has no effect on pain in polyneuropathy , 2004, Neurology.

[72]  T. Jensen,et al.  Antidepressants in the treatment of neuropathic pain. , 2005, Basic & clinical pharmacology & toxicology.

[73]  Sheena Derry,et al.  Systematic review of topical capsaicin for the treatment of chronic pain , 2004, BMJ : British Medical Journal.

[74]  J. Hippisley-Cox,et al.  Antidepressants as risk factor for ischaemic heart disease: case-control study in primary care , 2001, BMJ : British Medical Journal.

[75]  M. Rowbotham,et al.  Treatment response in antidepressant-naïve postherpetic neuralgia patients: double-blind, randomized trial. , 2005, The journal of pain : official journal of the American Pain Society.

[76]  D. Gavaghan,et al.  Pooling data for Number Needed to Treat: no problems for apples , 2002, BMC medical research methodology.

[77]  T. Jensen,et al.  Pharmacologic treatment of pain in polyneuropathy , 2000, Neurology.

[78]  David Moher,et al.  The CONSORT statement: revised recommendations for improving the quality of reports of parallel group randomized trials , 2001, Annals of Internal Medicine.

[79]  J. O'Brien,et al.  Induced Pain Referral from Posterior Lumbar Elements in Normal Subjects , 1979, Spine.

[80]  R. Hubbard,et al.  General population based study of the impact of tricyclic and selective serotonin reuptake inhibitor antidepressants on the risk of acute myocardial infarction , 2005, Heart.

[81]  R. Dubner,et al.  Efficacy of desipramine in painful diabetic neuropathy: a placebo-controlled trial , 1991, Pain.

[82]  M. Bone,et al.  Gabapentin in Postamputation Phantom Limb Pain: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Study , 2002, Regional Anesthesia & Pain Medicine.

[83]  A. Beydoun,et al.  Gabapentin for the Symptomatic Treatment of Painful Neuropathy in Patients With Diabetes Mellitus: a Randomized Controlled Trial , 1999 .

[84]  J. Vanneste,et al.  Randomised double-blind active-placebo-controlled crossover trial of intravenous fentanyl in neuropathic pain , 1997, The Lancet.

[85]  H. Schumacher,et al.  Mexiletine in the Treatment of Diabetic Neuropathy , 1992, Diabetes Care.

[86]  P. Schwenkreis,et al.  Efficacy of the NMDA-receptor antagonist memantine in patients with chronic phantom limb pain – results of a randomized double-blinded, placebo-controlled trial , 2003, Pain.

[87]  K. Zilkha,et al.  Clinical trial of carbazepine (tegretol) in trigeminal neuralgia. , 1966, Journal of neurology, neurosurgery, and psychiatry.

[88]  S. Kochar,et al.  Divalproex sodium in the management of post-herpetic neuralgia: a randomized double-blind placebo-controlled study. , 2005, QJM : monthly journal of the Association of Physicians.

[89]  D. A. Simpson Gabapentin and Venlafaxine for the Treatment of Painful Diabetic Neuropathy , 2001, Journal of clinical neuromuscular disease.

[90]  K. F. Bach,et al.  Good Clinical Practice is now Obligatory in Academic Clinical Drug Research in the European Union , 2004, Basic & clinical pharmacology & toxicology.

[91]  M. Rowbotham,et al.  Topical lidocaine patch relieves postherpetic neuralgia more effectively than a vehicle topical patch: results of an enriched enrollment study , 1999, Pain.

[92]  T. D. Wilton Tegretol in the treatment of diabetic neuropathy. , 1974, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde.

[93]  A. Gammaitoni,et al.  Pharmacokinetics and Tolerability of Lidocaine Patch 5% with Extended Dosing , 2002, The Annals of pharmacotherapy.

[94]  Scheffler Nm,et al.  Treatment of painful diabetic neuropathy with capsaicin 0.075%. , 1991, Journal of the American Podiatric Medical Association.

[95]  M. Rowbotham,et al.  Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. , 1998, JAMA.

[96]  C. Wilder-Smith,et al.  Postamputation Pain and Sensory Changes in Treatment-naive Patients: Characteristics and Responses to Treatment with Tramadol, Amitriptyline, and Placebo , 2005, Anesthesiology.

[97]  A. Drewes,et al.  Valproate for treatment of chronic central pain after spinal cord injury. A double-blind cross-over study , 1994, Paraplegia.

[98]  M. Max,et al.  Topiramate in chronic lumbar radicular pain. , 2005, The journal of pain : official journal of the American Pain Society.

[99]  Sharon M. Watanabe Lamotrigine reduces painful diabetic neuropathy : a randomized , controlled study , 2003 .

[100]  T. Jensen,et al.  Symptoms and signs in patients with suspected neuropathic pain , 2004, Pain.

[101]  M. Max,et al.  Dextromethorphan and Memantine in Painful Diabetic Neuropathy and Postherpetic Neuralgia: Efficacy and Dose-Response Trials , 2002, Anesthesiology.

[102]  F. Boureau,et al.  Tramadol in post-herpetic neuralgia: a randomized, double-blind, placebo-controlled trial , 2003, Pain.

[103]  D. Selvarajah,et al.  Morphine, gabapentin, or their combination for neuropathic pain. , 2005, The New England journal of medicine.

[104]  P. Siddall,et al.  Pregabalin in central neuropathic pain associated with spinal cord injury , 2006, Neurology.

[105]  S. Sherman,et al.  Double-blind, randomized trial of bupropion SR for the treatment of neuropathic pain , 2001, Neurology.

[106]  Memantine (a N-Methyl-d-Aspartate Receptor Antagonist) in the Treatment of Neuropathic Pain After Amputation or Surgery: A Randomized, Double-Blinded, Cross-Over Study , 2000, Anesthesia and analgesia.

[107]  L. Vernich,et al.  Nortriptyline versus amitriptyline in postherpetic neuralgia , 1998, Neurology.

[108]  H. J. McQuay,et al.  A systematic review of antidepressants in neuropathic pain , 1996, Pain.

[109]  R. Baron,et al.  Translation of symptoms and signs into mechanisms in neuropathic pain , 2003, Pain.

[110]  R. Moore,et al.  Teasing apart quality and validity in systematic reviews: an example from acupuncture trials in chronic neck and back pain , 2000, Pain.

[111]  William H. Calvin,et al.  Mechanosensitivity of dorsal root ganglia and chronically injured axons: A physiological basis for the radicular pain of nerve root compression , 1977, Pain.

[112]  J. Kastrup,et al.  MEXILETINE FOR TREATMENT OF CHRONIC PAINFUL DIABETIC NEUROPATHY , 1988, The Lancet.

[113]  A. Furlan,et al.  Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects , 2006, Canadian Medical Association Journal.

[114]  R. Mann,et al.  Safety of Long‐Term Lamotrigine in Epilepsy , 1997, Epilepsia.

[115]  Namita Singh,et al.  Gabapentin for the Treatment of Pain in Guillain-Barré Syndrome: A Double-Blinded, Placebo-Controlled, Crossover Study , 2002, Anesthesia and analgesia.

[116]  Lucy L Chen,et al.  Opioid tolerance and hyperalgesia. , 2007, The Medical clinics of North America.

[117]  Steven Kirshblum,et al.  Gabapentin In The Treatment Of Neuropathic Pain After Spinal Cord Injury: A Prospective, Randomized, Double-Blind, Crossover Trial , 2002, The journal of spinal cord medicine.

[118]  A. Rajput,et al.  Polyneuropathy. , 2020, Canadian family physician Medecin de famille canadien.

[119]  R. Jameson,et al.  Experiments on pain referred from deep somatic tissues. , 1954, The Journal of bone and joint surgery. American volume.

[120]  C Peter N Watson,et al.  The postmastectomy pain syndrome and topical capsaicin: a randomized trial , 1992, Pain.

[121]  A. Vinik,et al.  Lamotrigine for treatment of pain associated with diabetic neuropathy: Results of two randomized, double-blind, placebo-controlled studies , 2007, Pain.

[122]  Bridget A. Martell,et al.  Systematic Review: Opioid Treatment for Chronic Back Pain: Prevalence, Efficacy, and Association with Addiction , 2007, Annals of Internal Medicine.

[123]  S. Werns,et al.  Phenytoin in the treatment of diabetic symmetrical polyneuropathy , 1977, Clinical pharmacology and therapeutics.

[124]  N. Bogduk,et al.  Clinical Features of Patients with Pain Stemming from the Lumbar Zygapophysial Joints: Is the Lumbar Facet Syndrome a Clinical Entity? , 1994, Spine.

[125]  M. Chipman,et al.  Chronic noncancer pain and the long term utility of opioids. , 2004, Pain research & management.

[126]  E. Chaney,et al.  The use of oral mexiletine for the treatment of pain after peripheral nerve injury. , 1992, Anesthesiology.

[127]  M. Versavel,et al.  Pregabalin reduces pain and improves sleep and mood disturbances in patients with post-herpetic neuralgia: results of a randomised, placebo-controlled clinical trial , 2004, Pain.

[128]  M. Rowbotham,et al.  Lidocaine patch: double-blind controlled study of a new treatment method for post-herpetic neuralgia , 1996, Pain.

[129]  E. Kalso,et al.  Recommendations for using opioids in chronic non‐cancer pain , 2003, European journal of pain.

[130]  M. Serpell Gabapentin in neuropathic pain syndromes: a randomised, double-blind, placebo-controlled trial , 2002, Pain.

[131]  M. Rowbotham,et al.  A multicenter, double-blind, randomized, placebo-controlled crossover evaluation of a short course of 4030W92 in patients with chronic neuropathic pain. , 2002, The journal of pain : official journal of the American Pain Society.

[132]  S. Tuel,et al.  Effect of mexiletine on spinal cord injury dysesthetic pain. , 1996, American journal of physical medicine & rehabilitation.

[133]  Smriti Iyengar,et al.  Duloxetine versus routine care in the long-term management of diabetic peripheral neuropathic pain. , 2006, Journal of palliative medicine.

[134]  John Hoey,et al.  Clinical trial registration: a statement from the International Committee of Medical Journal Editors. , 2005, Circulation.

[135]  C. Warms,et al.  Efficacy of amitriptyline for relief of pain in spinal cord injury: results of a randomized controlled trial , 2002, Pain.

[136]  F. Gómez-Pérez,et al.  Nortriptyline and fluphenazine in the symptomatic treatment of diabetic neuropathy. A double-blind cross-over study , 1985, Pain.

[137]  H. J. McQuay,et al.  Algorithm for neuropathic pain treatment: An evidence based proposal , 2005, Pain.

[138]  H. Ugurlu,et al.  Gabapentin Is a First Line Drug for the Treatment of Neuropathic Pain in Spinal Cord Injury , 2004, Spine.

[139]  T. Cascino,et al.  Phase III placebo-controlled trial of capsaicin cream in the management of surgical neuropathic pain in cancer patients. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[140]  K. Brøsen,et al.  The selective serotonin reuptake inhibitor citalopram relieves the symptoms of diabetic neuropathy , 1992, Clinical pharmacology and therapeutics.

[141]  M. Rowbotham,et al.  Topical lidocaine gel relieves postherpetic neuralgia , 1995, Annals of neurology.

[142]  T. Gordh,et al.  Peripheral neuropathic pain—a multidimensional burden for patients , 2001, European journal of pain.

[143]  M. Fava,et al.  Emergence of adverse events following discontinuation of treatment with extended-release venlafaxine. , 1997, The American journal of psychiatry.

[144]  C Peter N Watson,et al.  Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia. , 1998, Neurology.

[145]  R. Dubner,et al.  Effects of Desipramine, Amitriptyline and Fluoxetine on Pain in Diabetic Neuropathy , 1993 .

[146]  R. Dworkin,et al.  The impact of neuropathic pain on health-related quality of life , 2007, Neurology.

[147]  I. Olkin,et al.  Improving the quality of reports of meta‐analyses of randomised controlled trials: the QUOROM statement , 2000, Revista espanola de salud publica.

[148]  R. Birch,et al.  Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial , 2004, Pain.

[149]  M. Rowbotham,et al.  Oral opioid therapy for chronic peripheral and central neuropathic pain. , 2003, The New England journal of medicine.

[150]  The Response of Neuropathic Pain and Pain in Complex Regional Pain Syndrome I to Carbamazepine and Sustained-Release Morphine in Patients Pretreated with Spinal Cord Stimulation: A Double-Blinded Randomized Study , 2001, Anesthesia and analgesia.

[151]  C. Woolf Dissecting out mechanisms responsible for peripheral neuropathic pain: implications for diagnosis and therapy. , 2004, Life sciences.

[152]  J. Mazzola,et al.  A randomized, placebo‐controlled study of oxcarbazepine in painful diabetic neuropathy , 2006, Acta neurologica Scandinavica.

[153]  S. Mercadante,et al.  Amitriptyline in Neuropathic Cancer Pain in Patients on Morphine Therapy: A Randomized Placebo-controlled, Double-blind Crossover Study , 2002, Tumori.

[154]  V. Chadda,et al.  Double blind study of the effects of diphenylhydantoin sodium on diabetic neuropathy. , 1978, The Journal of the Association of Physicians of India.

[155]  J. Rosenstock,et al.  Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial , 2004, Pain.

[156]  J. Oki,et al.  Mexiletine in the Symptomatic Treatment of Diabetic Peripheral Neuropathy , 1997, The Annals of pharmacotherapy.

[157]  D. Grothe,et al.  Treatment of Pain Syndromes with Venlafaxine , 2004, Pharmacotherapy.

[158]  I. L. Johannesen,et al.  Lamotrigine in spinal cord injury pain: a randomized controlled trial , 2002, Pain.

[159]  C. Yiannoutsos,et al.  A randomized trial of amitriptyline and mexiletine for painful neuropathy in HIV infection , 1998, Neurology.

[160]  D. Simpson,et al.  A placebo-controlled trial of lamotrigine for painful HIV-associated neuropathy , 2000, Neurology.

[161]  A. Jadad,et al.  Anticonvulsant drugs for acute and chronic pain. , 2010, The Cochrane database of systematic reviews.

[162]  P. Oskarsson,et al.  Efficacy and Safety of Mexiletine in the Treatment of Painful Diabetic Neuropathy. The Mexiletine Study Group , 1997, Diabetes Care.

[163]  A. M. Harvey Classification of Chronic Pain—Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms , 1995 .

[164]  A. Jadad,et al.  Dextromethorphan for the treatment of neuropathic pain: a double-blind randomised controlled crossover trial with integral n-of-1 design , 1994, Pain.

[165]  J C Fairbank,et al.  Apophyseal Injection of Local Anesthetic as a Diagnostic Aid in Primary Low‐Back Pain Syndromes , 1981, Spine.

[166]  P. Raskin,et al.  Topiramate vs placebo in painful diabetic neuropathy , 2004, Neurology.

[167]  T. Jensen,et al.  Lamotrigine for central poststroke pain: A randomized controlled trial , 2001 .

[168]  R. Portenoy,et al.  Controlled-release oxycodone for pain in diabetic neuropathy , 2003, Neurology.

[169]  P. Novotny,et al.  Phase III evaluation of nortriptyline for alleviation of symptoms of cis-platinum-induced peripheral neuropathy , 2002, Pain.

[170]  J. Ballantyne,et al.  Opioid dependence and addiction during opioid treatment of chronic pain , 2007, PAIN.

[171]  Miroslav Backonja,et al.  Gabapentin dosing for neuropathic pain: evidence from randomized, placebo-controlled clinical trials. , 2003, Clinical therapeutics.

[172]  U. Thienel,et al.  Topiramate in painful diabetic polyneuropathy: findings from three double‐blind placebo‐controlled trials , 2004, Acta neurologica Scandinavica.

[173]  M. Angst,et al.  Opioid-induced hyperalgesia: A qualitative systematic review , 2006 .

[174]  K. Chaloner,et al.  Acupuncture and amitriptyline for pain due to HIV-related peripheral neuropathy: a randomized controlled trial. Terry Beirn Community Programs for Clinical Research on AIDS. , 1998, JAMA.

[175]  E. Whalen,et al.  Efficacy of pregabalin in neuropathic pain evaluated in a 12-week, randomised, double-blind, multicentre, placebo-controlled trial of flexible- and fixed-dose regimens , 2005, Pain.

[176]  W. Rand,et al.  Gabapentin in the treatment of painful diabetic neuropathy: a placebo controlled, double blind, crossover trial , 1999, Journal of neurology, neurosurgery, and psychiatry.

[177]  T. Nurmikko,et al.  EFNS guidelines on pharmacological treatment of neuropathic pain , 2006, European journal of neurology.

[178]  W. Weber,et al.  Randomised controlled trial of gabapentin in Complex Regional Pain Syndrome type 1 [ ISRCTN 84121379 ] , 2004 .

[179]  M. Alderman,et al.  Excess risk of myocardial infarction in patients treated with antidepressant medications: association with use of tricyclic agents. , 2000, The American journal of medicine.

[180]  K. Tyler,et al.  A randomized vehicle-controlled trial of topical capsaicin in the treatment of postherpetic neuralgia. , 1993, Clinical therapeutics.

[181]  L. Lamoreaux,et al.  Relief of painful diabetic peripheral neuropathy with pregabalin: a randomized, placebo-controlled trial. , 2005, The journal of pain : official journal of the American Pain Society.

[182]  M. Detke,et al.  Duloxetine vs. placebo in patients with painful diabetic neuropathy , 2005, Pain.

[183]  D. Kondziolka,et al.  The effect of single-application topical ophthalmic anesthesia in patients with trigeminal neuralgia. A randomized double-blind placebo-controlled trial. , 1994, Journal of neurosurgery.

[184]  Grethe Andersen,et al.  Tramadol relieves pain and allodynia in polyneuropathy: a randomised, double-blind, controlled trial , 1999, PAIN.

[185]  N. Finnerup,et al.  Spinal cord injury pain – mechanisms and treatment , 2004, European journal of neurology.

[186]  E. Carrazana,et al.  Rationale and evidence for the use of oxcarbazepine in neuropathic pain. , 2003, Journal of pain and symptom management.

[187]  K A L'Abbé,et al.  Meta-analysis in clinical research. , 1987, Annals of internal medicine.

[188]  R. Poole,et al.  Pregabalin relieves symptoms of painful diabetic neuropathy , 2004, Neurology.

[189]  J. Dvořák Neurophysiologic tests in diagnosis of nerve root compression caused by disc herniation. , 1996, Spine.

[190]  G. Woody,et al.  A comparison of the abuse liability of tramadol, NSAIDs, and hydrocodone in patients with chronic pain. , 2006, Journal of pain and symptom management.

[191]  P. Hansson Neuropathic pain : pathophysiology and treatment , 2001 .

[192]  Amitriptyline, but not lorazepam, relieves postherpetic neuralgia , 1988, Neurology.

[193]  J. Bogousslavsky,et al.  Efficacy of lidocaine patch 5% in the treatment of focal peripheral neuropathic pain syndromes: a randomized, double-blind, placebo-controlled study , 2003, Pain.

[194]  J. Wernicke,et al.  A randomized controlled trial of duloxetine in diabetic peripheral neuropathic pain , 2006, Neurology.

[195]  R. Derby,et al.  Disc Stimulation and Patterns of Referred Pain , 2002, Spine.

[196]  K. Murray,et al.  Cyclic antidepressants and the risk of sudden cardiac death , 2004, Clinical pharmacology and therapeutics.

[197]  D. Tarsy,et al.  Does capsaicin relieve the pain of diabetic neuropathy? , 1990, Pain.

[198]  E. Bruera,et al.  Symptomatic hypogonadism in male survivors of cancer with chronic exposure to opioids , 2004, Cancer.

[199]  A. Fro̸land,et al.  Imipramine treatment of painful diabetic neuropathy. , 1984, JAMA.

[200]  S. Kasper,et al.  Efficacy and safety of pregabalin in the treatment of generalized anxiety disorder: a 6-week, multicenter, randomized, double-blind, placebo-controlled comparison of pregabalin and venlafaxine. , 2006, The Journal of clinical psychiatry.

[201]  M. Hüppe,et al.  Reduktion chronischer Schmerzen bei nichtpostherpetischen peripheren Neuropathien nach topischer Behandlung mit Lidocainpflaster , 2004, Der Schmerz.

[202]  L. Manchikanti,et al.  Controlled substance abuse and illicit drug use in chronic pain patients: An evaluation of multiple variables. , 2006, Pain physician.

[203]  M. Rowbotham,et al.  A randomized, double-blind, placebo-controlled trial of a glycine antagonist in neuropathic pain , 2002, Neurology.

[204]  E. Eisenberg,et al.  Efficacy and safety of opioid agonists in the treatment of neuropathic pain of nonmalignant origin: systematic review and meta-analysis of randomized controlled trials. , 2005, JAMA.

[205]  D. Simpson,et al.  A Randomized Controlled Trial of 5% Lidocaine Gel for HIV-Associated Distal Symmetric Polyneuropathy , 2004, Journal of acquired immune deficiency syndromes.

[206]  M. Pollack,et al.  Pregabalin for treatment of generalized anxiety disorder: a 4-week, multicenter, double-blind, placebo-controlled trial of pregabalin and alprazolam. , 2005, Archives of general psychiatry.

[207]  A. Sanabria,et al.  Randomized controlled trial. , 2005, World journal of surgery.

[208]  G. Cruccu,et al.  EFNS guidelines on neuropathic pain assessment , 2004, European journal of neurology.

[209]  A. Beydoun,et al.  Oxcarbazepine in painful diabetic neuropathy: results of a dose‐ranging study , 2006, Acta neurologica Scandinavica.

[210]  L. Arendt-Nielsen,et al.  The effect of venlafaxine on ongoing and experimentally induced pain in neuropathic pain patients: a double blind, placebo controlled study , 2005, European journal of pain.

[211]  G. McCleane 200 mg daily of lamotrigine has no analgesic effect in neuropathic pain: a randomised, double-blind, placebo controlled trial , 1999, PAIN.

[212]  J. Fortin,et al.  Sacroiliac Joint: Pain Referral Maps Upon Applying a New Injection/Arthrography Technique Part I Asymptomatic Volunteers , 1994, Spine.

[213]  M. Janko,et al.  The spinal nerve root "innervation", and a new concept of the clinicopathological interrelations in back pain and sciatica. , 1981, Neurochirurgia.

[214]  A. Panerai,et al.  A randomized, within‐patient, cross‐over, placebo‐controlled trial on the efficacy and tolerability of the tricyclic antidepressants chlorimipramine and nortriptyline in central pain , 1990, Acta neurologica Scandinavica.

[215]  Dawn Carroll,et al.  Anticonvulsant drugs for management of pain: a systematic review , 1995, BMJ.

[216]  P. Manfredi Opioids versus antidepressants in postherpetic neuralgia: A randomized, placebo-controlled trial , 2003, Neurology.

[217]  M. Angst,et al.  Opioid tolerance and hyperalgesia in chronic pain patients after one month of oral morphine therapy: a preliminary prospective study. , 2006, The journal of pain : official journal of the American Pain Society.

[218]  J. Zacny Profiling the subjective, psychomotor, and physiological effects of tramadol in recreational drug users. , 2005, Drug and alcohol dependence.

[219]  C. Sang NMDA-receptor antagonists in neuropathic pain: experimental methods to clinical trials. , 2000, Journal of pain and symptom management.

[220]  I. Olkin,et al.  Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement , 1999, The Lancet.

[221]  H. Beck-Nielsen,et al.  Clomipramine vs desipramine vs placebo in the treatment of diabetic neuropathy symptoms. A double-blind cross-over study. , 1990, British journal of clinical pharmacology.

[222]  T. Nurmikko,et al.  Lamotrigine (Lamictal) in refractory trigeminal neuralgia: results from a double-blind placebo controlled crossover trial , 1997, Pain.

[223]  T. Jensen,et al.  The clinical picture of neuropathic pain. , 2001, European journal of pharmacology.

[224]  Mario Saltarelli,et al.  Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations. , 2003, Archives of neurology.

[225]  J. Czerniecki,et al.  Efficacy of gabapentin in treating chronic phantom limb and residual limb pain. , 2005, Journal of rehabilitation research and development.

[226]  E. H. Davis,et al.  Controlled sequential trials of carbamazepine in trigeminal neuralgia. , 1966, Archives of neurology.

[227]  K. Brøsen,et al.  The selective serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symptoms , 1990, Pain.

[228]  J. Czerniecki,et al.  Trial of amitriptyline for relief of pain in amputees: results of a randomized controlled study. , 2004, Archives of physical medicine and rehabilitation.

[229]  B. Pollock,et al.  Comparison of paroxetine and nortriptyline in depressed patients with ischemic heart disease. , 1998, JAMA.

[230]  G. McCleane Intravenous infusion of phenytoin relieves neuropathic pain: a randomized, double-blinded, placebo-controlled, crossover study. , 1999, Anesthesia and analgesia.

[231]  S. Shott,et al.  Topical capsaicin in the management of HIV-associated peripheral neuropathy. , 2000, Journal of pain and symptom management.

[232]  E. Kalso,et al.  Amitriptyline effectively relieves neuropathic pain following treatment of breast cancer. , 1996, Pain.

[233]  C. Kemper,et al.  Mexiletine for HIV-infected patients with painful peripheral neuropathy: a double-blind, placebo-controlled, crossover treatment trial. , 1998, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[234]  M. Rowbotham,et al.  Lack of efficacy of riluzole in the treatment of peripheral neuropathic pain conditions , 2000, Neurology.