J Korean Med Assoc Search


J Korean Med Assoc > Volume 55(6); 2012 > Article
Ko and Kim: The pharmacological management of neuropathic pain


Neuropathic pain has recently been defined as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system". Neuropathic pain is a debilitating chronic condition that remains very difficult to treat and challenging to manage. Tricyclic antidepressants (amitryptiline, nortriptyline, imipramine), selective serotonin and norepinephrine reuptake inhibitors (duloxetine, venlafaxine), anticonvulsants (gabapentin, pregabalin), and 5% lidocaine patches have demonstrated efficacy in neuropathic pain and are recommended as first-line medications. In patients who fail to respond to these first-line medications alone and/or in combination, opioid analgesics or tramadol can be used as a second-line treatment alone or in combination with one of the first-line medications. Opioid analgesics and tramadol can also be considered for first-line use in selected clinical circumstances. Other pharmacological therapeutic options include selective serotonin reuptake inhibitors, antiepileptic drugs (levetiracetam, lacosamide, lamotrigine, valproic acid), cannabinoids, high concentration capsaicin patch, and botulinum toxin A. Medication selection should be individualized, with side effects taken into consideration as well as potential beneficial or deleterious effects on comorbidities, and whether or not prompt onset of pain relief is necessary.


1. Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, Hansson P, Hughes R, Nurmikko T, Serra J. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 2008;70:1630-1635.

2. Bouhassira D, Lanteri-Minet M, Attal N, Laurent B, Touboul C. Prevalence of chronic pain with neuropathic characteristics in the general population. Pain 2008;136:380-387.

3. Freynhagen R, Baron R, Gockel U, Tolle TR. painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain. Curr Med Res Opin 2006;22:1911-1920.

4. Roose SP, Laghrissi-Thode F, Kennedy JS, Nelson JC, Bigger JT, Pollock BG, Gaffney A, Narayan M, Finkel MS, McCafferty J, Gergel I. Comparison of paroxetine and nortriptyline in depressed patients with ischemic heart disease. JAMA 1998;279:287-291.

5. Ray WA, Meredith S, Thapa PB, Hall K, Murray KT. Cyclic antidepressants and the risk of sudden cardiac death. Clin Pharmacol Ther 2004;75:234-241.

6. Finnerup NB, Sindrup SH, Jensen TS. The evidence for pharmacological treatment of neuropathic pain. Pain 2010;150:573-581.

7. Rowbotham MC, Goli V, Kunz NR, Lei D. Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study. Pain 2004;110:697-706.

8. Shaikh S, Yaacob HB, Abd Rahman RB. Lamotrigine for trigeminal neuralgia: efficacy and safety in comparison with carbamazepine. J Chin Med Assoc 2011;74:243-249.

9. Johannessen CU. Mechanisms of action of valproate: a commentatory. Neurochem Int 2000;37:103-110.

10. Finnerup NB, Grydehoj J, Bing J, Johannesen IL, Biering-Sorensen F, Sindrup SH, Jensen TS. Levetiracetam in spinal cord injury pain: a randomized controlled trial. Spinal Cord 2009;47:861-867.

11. Wymer JP, Simpson J, Sen D, Bongardt S. Lacosamide SP742 Study Group. Efficacy and safety of lacosamide in diabetic neuropathic pain: an 18-week double-blind placebo-controlled trial of fixed-dose regimens. Clin J Pain 2009;25:376-385.

12. Dworkin RH, O'Connor AB, Backonja M, Farrar JT, Finnerup NB, Jensen TS, Kalso EA, Loeser JD, Miaskowski C, Nurmikko TJ, Portenoy RK, Rice AS, Stacey BR, Treede RD, Turk DC, Wallace MS. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain 2007;132:237-251.

13. Wu CL, Agarwal S, Tella PK, Klick B, Clark MR, Haythornthwaite JA, Max MB, Raja SN. Morphine versus mexiletine for treatment of postamputation pain: a randomized, placebo-controlled, crossover trial. Anesthesiology 2008;109:289-296.

14. Attal N, Cruccu G, Baron R, Haanpaa M, Hansson P, Jensen TS, Nurmikko T. European Federation of Neurological Societies. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol 2010;17:1113-1123. e67-e88.

15. Benedetti F, Vighetti S, Amanzio M, Casadio C, Oliaro A, Bergamasco B, Maggi G. Dose-response relationship of opioids in nociceptive and neuropathic postoperative pain. Pain 1998;74:205-211.

16. Finnerup NB, Otto M, McQuay HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain 2005;118:289-305.

17. Wong GY, Gavva NR. Therapeutic potential of vanilloid receptor TRPV1 agonists and antagonists as analgesics: recent advances and setbacks. Brain Res Rev 2009;60:267-277.

18. Backonja M, Wallace MS, Blonsky ER, Cutler BJ, Malan P Jr, Rauck R, Tobias J. NGX-4010 C116 Study Group. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study. Lancet Neurol 2008;7:1106-1112.

19. Simpson DM, Brown S, Tobias J;. NGX-4010 C107 Study Group. Controlled trial of high-concentration capsaicin patch for treatment of painful HIV neuropathy. Neurology 2008;70:2305-2313.

20. Sim WS. Application of botulinum toxin in pain management. Korean J Pain 2011;24:1-6.

21. Aoki KR. Review of a proposed mechanism for the antinociceptive action of botulinum toxin type A. Neurotoxicology 2005;26:785-793.

22. Ranoux D, Attal N, Morain F, Bouhassira D. Botulinum toxin type A induces direct analgesic effects in chronic neuropathic pain. Ann Neurol 2008;64:274-283.

23. Yuan RY, Sheu JJ, Yu JM, Chen WT, Tseng IJ, Chang HH, Hu CJ. Botulinum toxin for diabetic neuropathic pain: a randomized double-blind crossover trial. Neurology 2009;72:1473-1478.

24. Dworkin RH, O'Connor AB, Audette J, Baron R, Gourlay GK, Haanpaa ML, Kent JL, Krane EJ, Lebel AA, Levy RM, Mackey SC, Mayer J, Miaskowski C, Raja SN, Rice AS, Schmader KE, Stacey B, Stanos S, Treede RD, Turk DC, Walco GA, Wells CD. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc 2010;85:3 Suppl. S3-S14.

25. Jo HR, Chae YK, Kim YH, Chai HS, Lee WK, Choi SS, Min JH, Choi IG, Choi YS. Remifentanil-induced pronociceptive effect and its prevention with pregabalin. Korean J Anesthesiol 2011;60:198-204.

26. Gilron I, Bailey JM, Tu D, Holden RR, Jackson AC, Houlden RL. Nortriptyline and gabapentin, alone and in combination for neuropathic pain: a double-blind, randomised controlled crossover trial. Lancet 2009;374:1252-1261.

27. Hanna M, O'Brien C, Wilson MC. Prolonged-release oxycodone enhances the effects of existing gabapentin therapy in painful diabetic neuropathy patients. Eur J Pain 2008;12:804-813.

28. Arai YC, Matsubara T, Shimo K, Suetomi K, Nishihara M, Ushida T, Kobayashi K, Suzuki C, Kinoshita A, Kondo M, Matsubara S, Hayashi R, Tohyama Y, Nishida K, Arakawa M. Low-dose gabapentin as useful adjuvant to opioids for neuropathic cancer pain when combined with low-dose imipramine. J Anesth 2010;24:407-410.

29. Baron R, Mayoral V, Leijon G, Binder A, Steigerwald I, Serpell M. Efficacy and safety of combination therapy with 5% lido-caine medicated plaster and pregabalin in post-herpetic neuralgia and diabetic polyneuropathy. Curr Med Res Opin 2009;25:1677-1687.

Table 1
Classifications of neuropathic pain
Table 2
First-line medications to treat neuropathic pain

GI, gastrointestinal; HR, heart rate; BP, blood pressure; ECG, electrocardiogram; SSRI, selective serotonin reuptake inhibitor; SSNRI, selective serotonin and norepinephrine reuptake inhibitor; TCA, tricyclic antidepressant.


Browse all articles >

Editorial Office
37 Ichon-ro 46-gil, Yongsan-gu, Seoul
Tel: +82-2-6350-6562    Fax: +82-2-792-5208    E-mail: jkmamaster@gmail.com                

Copyright © 2024 by Korean Medical Association.

Developed in M2PI

Close layer
prev next